Venous thromboembolism guideline consultation

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Venous thromboembolism guideline consultation
DRAFT FOR CONSULTATION
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National Clinical Guideline developed by the National Collaborating
Centre for Acute Care.
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Venous Thromboembolism
The prevention of venous
thromboembolism (deep vein thrombosis
and pulmonary embolism) in patients
undergoing orthopaedic surgery and other
high-risk surgical procedures.
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Appendices A–G
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Contents
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3
A
SCOPE
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B
DECLARATIONS OF INTERESTS
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C
SEARCH STRATEGIES
226
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D
EVIDENCE TABLES
243
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E
META-ANALYSES FOREST PLOTS
531
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9
F
MIXED TREATMENT COMPARISON META-ANALYSIS
METHODS
626
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G
COST-EFFECTIVENESS ANALYSIS METHODS
633
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APPENDIX A
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NATIONAL INSTITUTE FOR CLINICAL EXCELLENCE
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SCOPE
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Venous thromboembolism: the prevention of venous thromboembolism (deep
vein thrombosis and pulmonary embolism) in patients undergoing orthopaedic
surgery and other high-risk surgical procedures.
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1.1
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Guideline title
Short title
Venous thromboembolism
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Background
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(a)
The National Institute for Clinical Excellence (‘NICE’ or ‘the Institute’)
has commissioned the National Collaborating Centre for Acute Care to
develop a clinical guideline on the prevention of venous thromboembolism for
use in the NHS in England and Wales. This follows referral of the topic by the
Department of Health and Welsh Assembly Government (see Appendix
[section 6]). The guideline will provide recommendations for good practice that
are based on the best available evidence of clinical and cost effectiveness.
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(b)
The Institute’s clinical guidelines will support the implementation of
National Service Frameworks (NSFs) in those aspects of care where a
Framework has been published. The statements in each NSF reflect the
evidence that was used at the time the Framework was prepared. The clinical
guidelines and technology appraisals published by the Institute after an NSF
has been issued will have the effect of updating the Framework.
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(c)
NICE clinical guidelines support the role of healthcare professionals in
providing care in partnership with patients, taking account of their individual
needs and preferences, and ensuring that patients (and their carers and
families, where appropriate) can make informed decisions about their care
and treatment.
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Clinical need for the guideline
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(a)
Deep vein thrombosis occurs in about 30% of surgical patients and is
commonly asymptomatic. However, the condition can lead to sudden death
due to pulmonary embolism, or cause long-term morbidity due to chronic
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venous insufficiency, potentially leading to venous ulceration and
development of a post-thrombotic limb.
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(b)
Most thrombi occur in the deep veins of the legs. Formation of thrombi
is associated with inactivity and high-risk surgical procedures. The risk is
particularly high in patients undergoing orthopaedic surgery and lengthy
operations. Previous studies have estimated the risk of fatal pulmonary
embolism following high-risk surgery to be between 1 and 5%.
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(c)
Current preventative measures for patients undergoing high-risk
surgical procedures include mechanical prophylaxis (such as graduated
elastic compression stockings) and pharmaceutical prophylaxis (such as low
molecular weight heparin). Clinical practice varies and it is estimated that 4
out of 10 orthopaedic patients do not receive any form of prophylaxis 1.
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(d)
This guideline will examine the risk of venous thromboembolism and
assess the evidence for preventative measures. It will provide
recommendations on the most clinically and cost effective measures to
reduce adverse events and morbidity and mortality.
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The guideline
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(a)
The guideline development process is described in detail in two
publications which are available from the NICE website (see ‘Further
information’). ‘The Guideline Development Process – An Overview for
Stakeholders, the Public and the NHS describes how organisations can
become involved in the development of a guideline. Guideline Development
Methods – Information for National Collaborating Centres and Guideline
Developers provides advice on the technical aspects of guideline
development.
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(b)
This document is the scope. It defines exactly what this guideline will
(and will not) examine, and what the guideline developers will consider. The
scope is based on the referral from the Department of Health and Welsh
Assembly Government (see Appendix [section 6]).
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(c)
The areas that will be addressed by the guideline are described in the
following sections.
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4.1
Population
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4.1.1
Groups that will be covered
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(a)
The guidelines will cover adults (age 18 and older) undergoing surgical
procedures that carry a high risk of venous thromboembolism, including:
1
Department of Health (2003) Further action to tackle post-code lottery in care [press
release]. http://www.dh.gov.uk
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•
orthopaedic surgery (for example, total hip or knee replacement,
surgery for hip fracture)
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•
major general surgery
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major gynaecological surgery (but not elective or emergency
Caesarean)
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urological surgery (including major or open urological procedures)
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neurosurgery
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cardiothoracic surgery
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major peripheral vascular surgery.
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4.1.2
Groups that will not be covered
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(a)
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(b)
Adult patients who are at a high risk of developing venous
thromboembolism but are not undergoing surgery will not be covered. For
example, the following circumstances and patients will be excluded from the
guideline (unless patients are undergoing one of the surgical procedures
listed in section 4.1.1):
Patients under the age of 18 will not be covered.
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patients with acute myocardial infarction
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patients who have had an acute stroke
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patients with cancer, including those being treated with chemotherapy
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pregnancy and the puerperium
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use of oral contraceptives and hormone replacement therapy
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long-distance travel.
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4.2
Healthcare setting
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The guideline will offer guidance for use in primary, secondary and tertiary
care.
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4.3
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(a)
The guideline will assess the risk factors associated with development
of venous thromboembolism in the surgical procedures listed in section 4.1.1.
The likelihood of developing venous thromboembolism will be assessed
according to risk factors associated with the individual as well as the type of
surgical procedure, and this will involve categorising patients according to
their level of risk of developing venous thromboembolism post-operatively.
Clinical management
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(b)
The guideline will assess the type of prophylaxis each individual patient
will require and the duration for which it should be carried out.
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(c)
The guideline will review the clinical and cost effectiveness, and
possible morbidity, of interventions to prevent venous thromboembolism in
patients undergoing the high-risk surgical procedures outlined in section 4.1.1.
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(d)
Interventions that will be considered include, for example:
•
7
mechanical:
8
-
graduated elastic compression stockings
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intermittent pneumatic compression devices (for example,
foot pumps)
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vena caval filters
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•
drugs/pharmacological:
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-
aspirin
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low-dose unfractionated heparin
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low molecular weight heparin
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synthetic pentasaccharide
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oral anticoagulants (warfarin)
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dextrans
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nursing care/physiotherapy:
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early mobilisation
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foot elevation
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hydration
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recent advances:
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for example, drugs licensed during the course of
guideline development.
(e)
Note that guideline recommendations on prescribing will normally fall
within licensed indications; exceptionally, and only where clearly supported by
evidence, use outside a licensed indication may be recommended. The
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guideline will assume that prescribers will use the Summary of Product
Characteristics to inform their decisions for individual patients.
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4.4
Status
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4.4.1
Scope
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This is the final draft of the scope.
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4.4.2
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The development of the guideline recommendations will begin in March 2005.
Guideline
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Further information
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The Scottish Intercollegiate Guidelines Network issued guidance on the use of
prophylaxis of venous thromboembolism in 2002 2.
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Information on the guideline development process is provided in:
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The Guideline Development Process – An overview for Stakeholders, the
public and the NHS
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Guideline Development Methods – Information for National Collaborating
Centres and Guideline Developers
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These booklets are available as PDF files from the NICE website
(www.nice.org.uk). Information on the progress of the guideline will also be
available from the website.
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Scottish Intercollegiate Guidelines Network (2002) Prophylaxis of venous thromboembolism.
SIGN Publication No. 62. Edinburgh: Scottish Intercollegiate Guidelines Network.
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Appendix – Referral from the Department of
Health and Welsh Assembly Government
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The Department of Health and Welsh Assembly Government asked the
Institute to develop a guideline with the following title and remit:
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Title: Venous thrombo-embolism: the prevention of venous thromboembolism in patients undergoing orthopaedic surgery and other high-risk
surgical procedures.
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Remit: To develop safety guidance for the NHS in England and Wales on
prophylaxis against venous thrombo-embolism (VTE) for patients undergoing
orthopaedic surgery and other surgical procedures for which there is a high
risk of VTE. The guidance should set out the principles of clinical and cost
effective practice and in particular should address:
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i the assessment of risk for particular procedures and for individual patients,
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ii the circumstances in which prophylaxis can be recommended as clinically
and cost effective, and
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iii the appropriate selection of interventions including both pharmaceutical
and mechanical methods of prophylaxis.
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APPENDIX B
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GDG members, expert advisors and staff declarations
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of interest
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Name
Interest
GDG Members
Tom Treasure
No interests were declared that required action
Ricky Autar
No interests were declared that required action
Colin Baigent
No interests were declared that required action
Robin Offord
No interests were declared that required action
David Farrell
None
Adam Thomas
None
John Luckit
No interests were declared that required action
Nigel Acheson
None
Simon Carter
No interests were declared that required action
Kim Carter
No interests were declared that required action
David Goldhill
No interests were declared that required action
Expert Advisors
Frank Smith
No interests were declared that required action
Tim Lees
No interests were declared that required action
David Whillier
No interests were declared that required action
Nihal Gurusinghe
None
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Name
Interest
NCC-AC Staff
Jennifer Hill
None
Phillipa Davies
No interests were declared that required action
Carlos Sharpin
None
David Wonderling
None
Enrico De Nigris
None
Peter B Katz
None
Clare Jones
No interests were declared that required action
Veena Mazarello Paes
None
Kathryn Oliver
None
Louise Thomas
None
Rifna Aktar
None
Susan Murray
No interests were declared that required action
Arash Rashidian
None
Sophie Capo-Bianco
None
Nishanthi Talawila
None
Kelly Dickinson
None
2
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APPENDIX C
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Search Strategies
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Searches were conducted in the following databases:
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Medline (Dialog Datastar) 1951 to 7 August 2006
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Embase (Dialog Datastar) 1974 to 7 August 2006
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•
Cinahl (Dialog Datastar) 1982 to 7 August 2006
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8
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The Cochrane Library Issue 3, 2006 (including NHS EED) to 7 August
2006
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Health Economic and Evaluations Database (HEED) to 7 August 2006
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Searches for interventions in Medline, Embase and Cinahl were constructed
using the following groups of search terms:
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•
Venous thromboembolism search terms
AND
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•
Surgical search terms
AND
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•
Intervention search terms
AND
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Study design search terms (i.e. systematic reviews, RCTs and
economic studies for Medline and Embase; systematic reviews and
RCTs for Cinahl)
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Searches for clinical evidence on interventions in The Cochrane Library were
constructed using the following groups of search terms:
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•
Venous thromboembolism search terms
AND
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•
Surgical search terms
AND
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•
Intervention search terms
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Searches for economic evidence in NHS EED and HEED were constructed
using the following groups of search terms:
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•
Venous thromboembolism search terms
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•
Surgical search terms
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29
AND
Patient views, information and education searches in Medline, Embase and
Cinahl were constructed using the following groups of search terms:
1. Venous thromboembolism search terms
AND
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2. Surgical search terms
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3. Patient information, patient views and education search terms
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AND
Terms for each of the above groups of terms are listed below
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5
Venous thromboembolism search terms
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Medline
1
Thromboembolism.DE. OR Venous-Thrombosis.DE. OR Pulmonary-Embolism.DE.
OR Thrombophlebitis.W..DE.
2
((venous OR vein) ADJ (thrombosis OR thrombus OR thromboembolism)).TI,AB. OR
(dvt OR vte).TI,AB. OR ((pulmonary OR lung) NEAR (embolism OR emboli) OR
thrombophlebitis).TI,AB.
3
1 OR 2
7
8
Embase
1
Thromboembolism.DE. OR Venous-Thromboembolism.DE. OR Vein-Thrombosis.DE.
OR Deep-Vein-Thrombosis.DE. OR Leg-Thrombosis.DE. OR PostoperativeThrombosis.DE. OR Lung-Embolism.DE. OR Thrombophlebitis.W..DE.
2
((venous OR vein) ADJ (thrombosis OR thrombus OR thromboembolism)).TI,AB. OR
(dvt OR vte).TI,AB. OR ((pulmonary OR lung) near (embolism OR emboli) OR
thrombophlebitis).TI,AB.
3
18 OR 19
9
10
Cinahl
1
Thromboembolism.DE. OR Venous-Thrombosis.DE. OR Pulmonary-Embolism.DE.
OR Thrombophlebitis.W..DE.
2
((venous OR vein) ADJ (thrombosis OR thrombus OR thromboembolism)).TI,AB. OR
(dvt OR vte).TI,AB. OR ((pulmonary OR lung) NEAR (embolism OR emboli) OR
thrombophlebitis).TI,AB.
3
1 OR 2
11
12
The Cochrane Library
1
MeSH descriptor Thromboembolism
2
MeSH descriptor Venous Thrombosis
3
MeSH descriptor Pulmonary Embolism
4
MeSH descriptor Thrombophlebitis
5
(*venous OR *vein) NEXT (thrombosis OR thrombus OR thromboembolism) OR dvt
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OR vte OR (pulmonary OR lung) NEAR (embolism or emboli) OR thrombophlebitis in
Title
6
(*venous OR *vein) NEXT (thrombosis OR thrombus OR thromboembolism) OR dvt
OR vte OR (pulmonary OR lung) NEAR (embolism or emboli) OR thrombophlebitis in
Abstract
7
#1 OR #2 OR #3 OR #4 OR #5 OR #6
1
2
Surgical search terms
3
Medline
1
Specialties-Surgical#.DE. OR Surgical-Procedures-Operative#.DE.
2
(surgical OR surgery OR neurosurgery OR neurosurgical OR operation OR operations
OR operative OR preoperative OR perioperative OR postoperative OR orthopaedic$
OR orthopedic$).TI,AB.
3
Su.DE.
4
(resect$ OR replacement$ OR excision$ OR arthroplasty).TI,AB.
5
1 OR 2 OR 3 OR 4
4
5
Embase
1
Surgery#.DE. OR Surgical-Science.DE. OR Orthopedics#.DE.
2
(surgical OR surgery OR neurosurgery OR neurosurgical OR operation OR operations
OR operative OR preoperative OR perioperative OR postoperative OR orthopaedic$
OR orthopedic$).TI,AB.
3
Su.DE.
4
(resect$ OR replacement$ OR excision$ OR arthroplasty).TI,AB.
5
1 OR 2 OR 3 OR 4
6
7
Cinahl
1
Surgery-Operative#.DE.
2
(surgical OR surgery OR neurosurgery OR neurosurgical OR operation OR operations
OR operative OR preoperative OR perioperative OR postoperative OR orthopaedic$
OR orthopedic$).TI,AB.
3
Su.DE.
4
(resect$ OR replacement$ OR excision$ OR arthroplasty).TI,AB.
5
1 OR 2 OR 3 OR 4
8
9
The Cochrane Library
1
MeSH descriptor Specialties, Surgical explode all trees
2
MeSH descriptor Surgical Procedures, Operative explode all trees
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surgical OR surgery OR neurosurgery OR neurosurgical OR operation OR operations
OR preoperative OR pre-operative OR perioperative OR peri-operative OR
postoperative OR post-operative OR orthopaedic* OR orthopedic* in Title
4
surgical OR surgery OR neurosurgery OR neurosurgical OR operation OR operations
OR preoperative OR pre-operative OR perioperative OR peri-operative OR
postoperative OR post-operative OR orthopaedic* OR orthopedic* in Abstract
5
Any MeSH descriptor with qualifier: SU
6
(resect* OR replacement* OR excision* OR arthroplasty) in Title
7
(resect* OR replacement* OR excision* OR arthroplasty) in Abstract
8
#1OR #2OR #3OR #4OR #5OR #6OR #7
1
2
Systematic review search terms
3
Medline
1
Meta-Analysis.DE. OR Review-Literature#.DE.
2
Meta-Analysis.PT. OR ((selection ADJ criteria).AB. OR (data ADJ extraction).AB.)
AND Review.PT.
3
(cochrane OR embase OR psychlit OR psyclit OR psychinfo OR psycinfo OR cinahl
OR cinhal OR science ADJ citation ADJ index OR bids OR cancerlit).AB.
4
(reference ADJ ('LIST' OR lists) OR bibliograph$ OR hand ADJ search$ OR manual
ADJ search$ OR relevant ADJ journals).AB.
5
meta ADJ (analysis OR analyse OR analyses OR analysed OR analytic$) OR
metaanaly$ OR meta-analy$ OR systematic ADJ (review OR overview)
6
1 OR 2 OR 3 OR 4 or 5
7
Comment.PT. OR Letter.PT. OR Editorial.PT. OR (Animals#.DE. NOT Humans.DE.)
8
6 NOT 7
4
5
Embase
1
Meta-Analysis#.DE.
2
((selection ADJ criteria).AB. OR (data ADJ extraction).AB.) AND Review.AT.
3
(cochrane OR embase OR psychlit OR psyclit OR psychinfo OR psycinfo OR cinahl
OR cinhal OR science ADJ citation ADJ index OR bids OR cancerlit).AB.
4
(reference ADJ ('LIST' OR lists) OR bibliograph$ OR hand ADJ search$ OR manual
ADJ search$ OR relevant ADJ journals).AB.
5
meta ADJ (analysis OR analyse OR analyses OR analysed OR analytic$) OR
metaanaly$ OR meta-analy$ OR systematic ADJ (review OR overview)
6
1 OR 2 OR 3 OR 4 OR 5
7
Letter.AT. OR Editorial.AT. OR ((Animal#.DE. OR Nonhuman.DE. OR AnimalExperiment#.DE.) NOT Human#.DE.)
8
6 NOT 7
6
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Cinahl
1
Meta-Analysis.DE. OR Literature-Review#.DE.
2
Systematic-Review.PT. OR ((selection ADJ criteria).AB. OR (data ADJ
extraction).AB.) AND Review.PT.
3
meta ADJ (analysis OR analyse OR analyses OR analysed OR analytic$) OR
metaanaly$ OR meta-analy$ OR systematic ADJ (review OR overview)
4
1 OR 2 OR 3
5
Commentary.PT. OR Letter.PT. OR Editorial.PT. OR Animals.DE.
6
4 NOT 5
2
3
Randomised controlled trial search terms
4
Medline
1
Randomized-Controlled-Trials.DE. OR Random-Allocation.DE. OR Double-BlindMethod.DE. OR Single-Blind-Method.DE. OR Clinical-Trials#.DE. OR Cross-OverStudies.DE. OR Prospective-Studies.DE. OR Placebos.DE.
2
Randomized-Controlled-Trial.PT. OR Clinical-Trial.PT. OR Controlled-Clinical-Trial.PT.
3
((clinical OR control OR controlled) ADJ (study OR trial) OR (single OR double OR
triple) ADJ (blind$3 OR mask$3) OR randomised OR randomized OR random$ WITH
(assign$ OR allocat$ OR group OR grouped OR patients OR study OR trial or
distribut$) OR crossover NEXT (design OR study OR trial) OR placebo OR
placebos).TI,AB.
4
1 OR 2 OR 3
5
Case-Reports.PT. NOT Randomized-Controlled-Trial.PT. OR Letter.PT. OR HistoricalArticle.PT. OR Review-Of-Reported-Cases.PT. OR Animals#.W..DE. NOT
Humans.DE.
6
4 NOT 5
5
6
Embase
1
Clinical-Trial.DE. OR Randomized-Controlled-Trial.DE. OR Randomization.W..DE. OR
Single-Blind-Procedure.DE. OR Double-Blind-Procedure.DE. OR CrossoverProcedure.DE. OR Prospective-Study.DE. OR Placebo.DE.
2
((clinical OR control OR controlled) ADJ (study OR trial) OR (single OR double OR
triple) ADJ (blind$3 OR mask$3) OR randomised OR randomized OR random$ WITH
(assign$ OR allocat$ OR group OR grouped OR patients OR study OR trial or
distribut$) OR crossover NEXT (design OR study OR trial) OR placebo OR
placebos).TI,AB.
3
1 OR 2
4
Case-Study.DE. OR case ADJ report OR Abstract-Report.DE. OR Letter.DE. OR
(Animal#.DE. OR Nonhuman.DE. OR Animal-Experiment#.DE.) NOT Human#.DE.
5
3 NOT 4
7
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Cinahl
1
Clinical-Trials#.DE. OR Random-Assignment.DE. OR Quantitative-Studies.DE. OR
Crossover-Design.DE. OR Placebos.DE.
2
Clinical-Trial.PT.
3
((clinical OR control OR controlled) ADJ (study OR trial) OR (single OR double OR
triple) ADJ (blind$3 OR mask$3) OR randomised OR randomized OR random$ WITH
(assign$ OR allocat$ OR group OR grouped OR patients OR study OR trial or
distribut$) OR crossover NEXT (design OR study OR trial) OR placebo OR
placebos).TI,AB.
4
1 OR 2 OR 3
2
3
Economic studies search terms
4
Medline
1
Economics.W..DE. OR Economics-Hospital#.DE. OR Economics-Medical#.DE. OR
Economics-Nursing.DE. OR Economics-Pharmaceutical.DE.
2
Costs-and-Cost-Analysis.DE. OR Cost-Allocation.DE. OR Cost-Benefit-Analysis.DE.
OR Cost-Control.DE. OR Cost-Savings.DE. OR Cost-Of-Illness.DE. OR CostSharing.DE. OR Health-Care-Costs.DE. OR Direct-Service-Costs.DE. OR DrugCosts.DE. OR Employer-Health-Costs.DE. OR Hospital-Costs.DE.
3
Health-Expenditures.DE. OR Capital-Expenditures.DE. OR Fees-and-Charges#.DE.
OR Budgets#.DE. OR Deductibles-and-Coinsurance.DE. OR Medical-SavingsAccounts.DE. OR Value-Of-Life.DE. OR Quality-Adjusted-Life-Years.DE.
4
((low OR high OR unit OR healthcare OR health ADJ care OR health-care OR hospital
OR benefit) ADJ (cost OR costs OR costing OR costings)).TI,AB. OR ((cost OR costs
OR costing OR costings) ADJ (estimat$ OR variable OR effectiv$ OR benefit$)).TI,AB.
5
fiscal OR funding OR financial OR finance OR economic$ OR pharmacoeconomic$
OR price OR prices OR pricing OR (QALY$ OR life-year$ OR costeffectiv$ OR costeffectiv$ OR costbenefit$ OR cost-benefit$).TI,AB.
6
1 OR 2 OR 3 OR 4 OR 5
5
6
Embase
1
Socioeconomics.W..DE. OR Cost-Benefit-Analysis.DE. OR Cost-EffectivenessAnalysis.DE. OR Cost-Of-Illness.DE. OR Cost-Control.DE. OR Economic-Aspect.DE.
OR Financial-Management.DE. OR Health-Care-Cost.DE. OR Health-CareFinancing.DE. OR Health-Economics.DE. OR Hospital-Cost.DE. OR CostMinimization-Analysis.DE.
2
fiscal OR financial OR finance OR funding OR (cost ADJ (estimate$ OR
variable$)).TI,AB. OR (unit ADJ (cost OR costs OR costing OR costings)).TI,AB.
3
1 OR 2
7
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Interventions search terms
2
Medline
1
Bandages.W..DE.
2
Intermittent-Pneumatic-Compression-Devices.DE.
3
(stocking OR stockings OR hose).TI,AB.
4
((calf OR elastic OR graded OR limb OR leg OR pneumatic OR plantar OR foot) ADJ
compression).TI,AB. OR (compression ADJ device).TI,AB.
5
(foot ADJ pump OR foot ADJ pumps).TI,AB.
6
flowtron.TI,AB.
7
Vena-Cava-Filters.DE.
8
((ivc OR vena ADJ (cava OR caval) OR greenfield) WITH (filter OR filters)).TI,AB.
9
Anticoagulants#.W..DE. OR Fibrinolytic-Agents#.DE. OR Antithrombins#.W..DE. OR
Platelet-Aggregation-Inhibitors#.DE.
10
(anticoagula$ OR anti ADJ coagula$ OR antithromb$ OR anti ADJ thrombin OR
antiemboli$ OR anti ADJ embolism OR anti ADJ embolic OR antiplatelet OR anti ADJ
platelet OR thrombin ADJ (inhibitor OR inhibition) OR direct ADJ thrombin).TI,AB.
11
Heparin.W..DE. OR Heparin-Low-Molecular-Weight.DE. OR Enoxaparin.W..DE. OR
Nadroparin.W..DE. OR Dalteparin.W..DE. OR Heparinoids.W..DE.
12
heparin OR heparinoid OR hirudoid OR antixarin OR ardeparin OR bemiparin OR
certoparin OR CY-222 OR dalteparin OR danaparoid OR embolex OR enoxaparin OR
fondaparinux OR fragmin OR idraparinux OR monoembolex OR nadroparin OR
parnaparin OR RD-11885 OR reviparin OR tedelparin OR tinzaparin OR suleparoide
13
Warfarin.W..DE. OR Coumarins.W..DE.
14
acenocoumarol OR brodifacoum OR bromadiolone OR cloricromen OR coumafos OR
coumadin OR coumarin OR coumatetralyl OR coumetarol OR dicoumarol OR
difenacoum OR ethyl-biscoumacetate OR flocoumafen OR galbanic-acid OR
nicoumalone OR phenindione OR phenprocoumon OR phepromaron OR tioclomarol
OR sinthrone OR warfarin
15
Hirudins.W..DE.
8
ximelagatran OR hirudin OR hirudins OR lepirudin OR argatroban OR melagatran OR
aripiprazole OR urokinase OR desirudin OR clopidogrel OR bivalirudin OR efegatran
9
pentasaccharide OR pentasaccharides
10
Dextrans#.W..DE.
11
dextran OR dextrans
12
Aspirin.W..DE.
13
aspirin OR acetylsalicylic ADJ acid
14
Dipyridamole.W..DE.
15
(clopidogrel OR dipyridamole).TI,AB.
16
Anesthesia-and-Analgesia.DE. OR Analgesia-Epidural.DE. OR Anesthesia.W..DE. OR
Anesthesia-Conduction#.DE.
17
(anaesthesia OR anesthesia OR anaesthetic$ OR anesthetic$ OR anaesthetise$ OR
anesthetise$ OR analgesi$ OR spinal OR epidural OR extradural).TI,AB.
18
Early-Ambulation.DE. OR Motion-Therapy-Continuous-Passive.DE. OR Bed-Rest.DE.
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19
(mobili$ OR physiotherapy OR ambulation OR kinetic ADJ therapy OR (continuous
OR lateral) ADJ rotation OR (therapeutic OR specialised OR specialized) ADJ bed OR
air ADJ loss ADJ mattress OR bed ADJ rest OR immobili$ OR leg ADJ
exercises).TI,AB.
20
Hindlimb-Suspension.DE.
21
((foot OR feet OR limb OR leg OR legs) NEAR (elevat$ OR raise$ OR
suspend$)).TI,AB.
22
Electric-Stimulation.DE. OR Electric-Stimulation-Therapy.DE.
23
((electric OR electrical OR electrically) NEXT (stimulation OR stimulator OR stimulated
OR stimulate)).TI,AB.
24
Colloids.W..DE. OR Hypertonic-Solutions.DE. OR Glucose-Solution-Hypertonic.DE.
OR Saline-Solution-Hypertonic.DE. OR Isotonic-Solutions.DE. OR RehydrationSolutions.DE. OR Water.W..DE. OR Body-Water.DE. OR Body-Fluids.DE.
25
Water-Electrolyte-Balance.DE. OR Water-Electrolyte-Imbalance.DE. OR
Dehydration.W..DE. OR Drinking.W..DE. OR Water-Deprivation.DE. OR InfusionsIntravenous.DE. OR Hemodilution.W..DE. OR Sodium-Lactate.DE. OR FluidTherapy.DE.
26
(colloid$ OR crystalloid$ OR saline OR glucose OR dextrose OR hypertonic OR
isotonic OR electrolyte ADJ (balance OR imbalance OR disturbance) OR water OR
hydrat$ OR dehydrat$ OR rehydrat$ OR drink$ OR fluid$1 OR haemodilut$ OR
hemodilut$ OR sodium ADJ lactate OR lactate ADJ sodium OR hartmann ADJ
solution OR ringer$ ADJ solution OR balanced ADJ salt ADJ solution).TI,AB.
27
1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 OR 8 OR 9 OR 10 OR 11 OR 12 OR 13 OR 14
OR 15 OR 16 OR 17 OR 18 OR 19 OR 20 OR 21 OR 22 OR 23 OR 24 OR 25 OR 26
1
2
Embase
1
Bandages-and-Dressings.DE. OR Bandage.W..DE.
2
(stocking OR stockings OR hose).TI,AB.
3
Pneumatic-Tool.DE. OR Leg-Compression.DE.
4
((calf OR elastic OR graded OR limb OR leg OR pneumatic OR plantar OR foot) ADJ
compression).TI,AB. OR (compression ADJ device).TI,AB.
5
(foot ADJ pump OR foot ADJ pumps).TI,AB.
6
flowtron.TI,AB.
7
Vena-Cava-Filter.DE.
8
((ivc OR vena ADJ (cava OR caval) OR greenfield) WITH (filter OR filters)).TI,AB.
9
Anticoagulant-Agent#.DE. OR Fibrinolytic-Agent#.DE. OR AntithrombocyticAgent#.DE. OR Thrombin-Inhibitor#.DE.
10
(anticoagula$ OR anti ADJ coagula$ OR antithromb$ OR anti ADJ thrombin OR
antiemboli$ OR anti ADJ embolism OR anti ADJ embolic OR antiplatelet OR anti ADJ
platelet OR thrombin ADJ (inhibitor OR inhibition) OR direct ADJ thrombin).TI,AB.
11
Heparin-Derivative.DE. OR Heparin.W..DE. OR Heparin-Calcium.DE. OR HeparinFraction.DE. OR Heparin-Fragment.DE. OR Hirudoid.W..DE. OR Low-MolecularWeight-Heparin#.DE. OR Suleparoide.W..DE.
12
heparin OR heparinoid OR hirudoid OR antixarin OR ardeparin OR bemiparin OR
certoparin OR CY-222 OR dalteparin OR danaparoid OR embolex OR enoxaparin OR
fondaparinux OR fragmin OR idraparinux OR monoembolex OR nadroparin OR
parnaparin OR RD-11885 OR reviparin OR tedelparin OR tinzaparin OR suleparoide
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13
Warfarin.W..DE. OR Coumarin.W..DE. OR Coumarin-Anticoagulant#.DE. OR
Coumarin-Derivative#.DE. OR Brodifacoum.W..DE. OR Bromadiolone.W..DE.
14
acenocoumarol OR brodifacoum OR bromadiolone OR cloricromen OR coumafos OR
coumadin OR coumarin OR coumatetralyl OR coumetarol OR dicoumarol OR
difenacoum OR ethyl-biscoumacetate OR flocoumafen OR galbanic-acid OR
nicoumalone OR phenindione OR phenprocoumon OR phepromaron OR tioclomarol
OR sinthrone OR warfarin
15
Hirudin.W..DE. OR Lepirudin.W..DE. OR Ximelagatran.W..DE.
16
ximelagatran OR hirudin OR hirudins OR lepirudin OR argatroban OR melagatran OR
aripiprazole OR urokinase OR desirudin OR clopidogrel OR bivalirudin OR efegatran
17
Pentasaccharide.W..DE.
18
pentasaccharide OR pentasaccharides
19
Dextran.W..DE. OR Dextran-40.DE. OR Dextran-60.DE. OR Dextran-70.DE.
20
dextran OR dextrans
21
Acetylsalicylic-Acid.DE.
22
aspirin OR acetylsalicylic ADJ acid
23
Clopidogrel.W..DE. OR Dipyridamole.W..DE.
24
(clopidogrel OR dipyridamole).TI,AB.
25
Anesthesia.W..DE. OR Epidural-Anesthesia#.DE. OR Local-Anesthesia#.DE. OR
Regional-Anesthesia#.DE.
26
(anaesthesia OR anesthesia OR anaesthetic$ OR anesthetic$ OR anaesthetise$ OR
anesthetise$ OR analgesi$ OR spinal OR epidural OR extradural).TI,AB.
27
Mobilization.W..DE. OR Passive-Movement.DE. OR Bed-Rest.DE.
28
(mobili$ OR physiotherapy OR ambulation OR kinetic ADJ therapy OR (continuous
OR lateral) ADJ rotation OR (therapeutic OR specialised OR specialized) ADJ bed OR
air ADJ loss ADJ mattress OR bed ADJ rest OR immobili$ OR leg ADJ
exercises).TI,AB.
29
((foot OR feet OR limb OR leg OR legs) NEAR (elevat$ OR raise$ OR
suspend$)).TI,AB.
30
electrostimulation.DE. OR electrostimulation-therapy.DE.
31
((electric OR electrical OR electrically) NEXT (stimulation OR stimulator OR stimulated
OR stimulate)).TI,AB.
32
Colloid.W..DE. OR Crystalloid.W..DE. OR Hypertonic-Solution.DE. OR
Glucose.W..DE. OR Sodium-Chloride.DE. OR Isotonic-Solution.DE. OR OralRehydration-Solution.DE. OR Water.W..DE. OR Total-Body-Water.DE. OR BodyWater.DE. OR Water-Absorption.DE. OR Fluid-Balance.DE. OR Fluid-Intake.DE.
33
Water-Deficit.DE. OR Water-Deprivation.DE. OR Fluid-Intake.DE. OR ElectrolyteBalance.DE. OR Electrolyte-Disturbance.DE. OR Dehydration.W..DE. OR
Drinking.W..DE. OR Water-Deprivation.DE. OR Hemodilution.W..DE. OR LactateSodium.DE. Or Hydration.W..DE.
34
(colloid$ OR crystalloid$ OR saline OR glucose OR dextrose OR hypertonic OR
isotonic OR electrolyte ADJ (balance OR imbalance OR disturbance) OR water OR
hydrat$ OR dehydrat$ OR rehydrat$ OR drink$ OR fluid$1 OR haemodilut$ OR
hemodilut$ OR sodium ADJ lactate OR lactate ADJ sodium OR hartmann ADJ
solution OR ringer$ ADJ solution OR balanced ADJ salt ADJ solution).TI,AB.
35
1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 OR 8 OR 9 OR 10 OR 11 OR 12 OR 13 OR 14
OR 15 OR 16 OR 17 OR 18 OR 19 OR 20 OR 21 OR 22 OR 23 OR 24 OR 25 OR 26
OR 27 OR 28 OR 29 OR 30 OR 31 OR 32 OR 33 OR 34
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1
2
Cinahl
1
Bandages-and-Dressings.DE. OR Compression-Garments.DE.
2
(stocking OR stockings OR hose).TI,AB.
3
Compression-Therapy.DE.
4
5
((calf OR elastic OR graded OR limb OR leg OR pneumatic OR plantar OR foot) ADJ
compression).TI,AB. OR (compression ADJ device).TI,AB.
(foot ADJ pump OR foot ADJ pumps).TI,AB.
6
flowtron.TI,AB.
7
8
9
10
11
12
13
14
15
16
Vena-Cava-Filters.DE.
((ivc OR vena ADJ (cava OR caval) OR greenfield) WITH (filter OR filters)).TI,AB.
Anticoagulants#.W..DE. OR Fibrinolytic-Agents#.DE. OR Platelet-AggregationInhibitors#.DE.
(anticoagula$ OR anti ADJ coagula$ OR antithromb$ OR anti ADJ thrombin OR
antiemboli$ OR anti ADJ embolism OR anti ADJ embolic OR antiplatelet OR anti ADJ
platelet OR thrombin ADJ (inhibitor OR inhibition) OR direct ADJ thrombin).TI,AB.
Heparin.W..DE. OR Heparin-Low-Molecular-Weight.DE. OR Heparinoids.W..DE.
heparin OR heparinoid OR hirudoid OR antixarin OR ardeparin OR bemiparin OR
certoparin OR CY-222 OR dalteparin OR danaparoid OR embolex OR enoxaparin OR
fondaparinux OR fragmin OR idraparinux OR monoembolex OR nadroparin OR
parnaparin OR RD-11885 OR reviparin OR tedelparin OR tinzaparin OR suleparoide
Warfarin.W..DE.
acenocoumarol OR brodifacoum OR bromadiolone OR cloricromen OR coumafos OR
coumadin OR coumarin OR coumatetralyl OR coumetarol OR dicoumarol OR
difenacoum OR ethyl-biscoumacetate OR flocoumafen OR galbanic-acid OR
nicoumalone OR phenindione OR phenprocoumon OR phepromaron OR tioclomarol
OR sinthrone OR warfarin
Hirudin.W..DE.
17
ximelagatran OR hirudin OR hirudins OR lepirudin OR argatroban OR melagatran OR
aripiprazole OR urokinase OR desirudin OR clopidogrel OR bivalirudin OR efegatran
pentasaccharide OR pentasaccharides
18
Dextrans.W..DE.
19
dextran OR dextrans
20
Aspirin.W..DE.
21
aspirin OR acetylsalicylic ADJ acid
22
Clopidogrel-Bisulfate.DE. OR Dipyridamole.W..DE.
23
(clopidogrel OR dipyridamole).TI,AB.
24
Anesthesia-And-Analgesia-Non-Cinahl#.DE. OR Anesthesia.W..DE. OR AnesthesiaConduction#.DE.
(anaesthesia OR anesthesia OR anaesthetic$ OR anesthetic$ OR anaesthetise$ OR
anesthetise$ OR analgesi$ OR spinal OR epidural OR extradural).TI,AB.
Early-Ambulation.DE. OR Bed-Rest.DE.
25
26
27
28
29
(mobili$ OR physiotherapy OR ambulation OR kinetic ADJ therapy OR (continuous OR
lateral) ADJ rotation OR (therapeutic OR specialised OR specialized) ADJ bed OR air
ADJ loss ADJ mattress OR bed ADJ rest OR immobili$ OR leg ADJ exercises).TI,AB.
((foot OR feet OR limb OR leg OR legs) NEAR (elevat$ OR raise$ OR
suspend$)).TI,AB.
Electric-Stimulation.DE.
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30
31
32
33
34
((electric OR electrical OR electrically) NEXT (stimulation OR stimulator OR stimulated
OR stimulate)).TI,AB.
Colloids.W..DE. OR Crystalloid-Solutions.DE. OR Hypertonic-Solutions.DE. OR
Glucose.W..DE. OR Saline-Solution-Hypertonic.DE. OR Isotonic-Solutions.DE. OR
Rehydration-Solutions.DE. OR Water.W..DE. OR Body-Water.DE. OR Body-Fluids.DE.
Fluid-Electrolyte-Balance.DE. OR Fluid-Electrolyte-Imbalance.DE. OR Fluid-Intake.DE.
OR Dehydration.W..DE. OR Infusions-Intravenous.DE. OR Hemodilution.W..DE. OR
Fluid-Therapy.DE.
(colloid$ OR crystalloid$ OR saline OR glucose OR dextrose OR hypertonic OR
isotonic OR electrolyte ADJ (balance OR imbalance OR disturbance) OR water OR
hydrat$ OR dehydrat$ OR rehydrat$ OR drink$ OR fluid$1 OR haemodilut$ OR
hemodilut$ OR sodium ADJ lactate OR lactate ADJ sodium OR hartmann ADJ solution
OR ringer$ ADJ solution OR balanced ADJ salt ADJ solution).TI,AB.
1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 OR 8 OR 9 OR 10 OR 11 OR 12 OR 13 OR 14
OR 15 OR 16 OR 17 OR 18 OR 19 OR 20 OR 21 OR 22 OR 23 OR 24 OR 25 OR 26
OR 27 OR 28 OR 29 OR 30 OR 31 OR 32 OR 33
1
2
The Cochrane Library
1
MeSH descriptor Bandages
2
MeSH descriptor Intermittent Pneumatic Compression Devices
3
(stocking OR stockings OR hose) in Record Title
4
(stocking OR stockings OR hose) in Abstract
5
(((calf OR elastic OR graded OR limb OR leg OR pneumatic OR plantar OR foot)
NEXT compression) OR (compression NEXT device)) in Record Title
6
(((calf OR elastic OR graded OR limb OR leg OR pneumatic OR plantar OR foot)
NEXT compression) OR (compression NEXT device)) in Abstract
7
(foot NEXT (pump OR pumps)) in Record Title
8
(foot NEXT (pump OR pumps)) in Abstract
9
flowtron in Record Title
10
flowtron in Abstract
11
MeSH descriptor Vena Cava Filters
12
((ivc OR (vena NEXT (cava OR caval)) OR greenfield) NEAR (filter OR filters)) in
Record Title
13
((ivc OR (vena NEXT (cava OR caval)) OR greenfield) NEAR (filter OR filters)) in
Abstract
16
MeSH descriptor Anticoagulants explode all trees
17
MeSH descriptor Fibrinolytic Agents explode all trees
18
MeSH descriptor Antithrombins explode all trees
19
MeSH descriptor Platelet Aggregation Inhibitors explode all trees
20
(anticoagula* OR anti NEXT coagula* OR antithromb* OR anti NEXT thrombin OR
antiemboli* OR anti NEXT embolism OR anti NEXT embolic OR antiplatelet OR anti
NEXT platelet OR thrombin NEXT (inhibitor OR inhibition) OR direct NEXT thrombin)
in Record Title
21
(anticoagula* OR anti NEXT coagula* OR antithromb* OR anti NEXT thrombin OR
antiemboli* OR anti NEXT embolism OR anti NEXT embolic OR antiplatelet OR anti
NEXT platelet OR thrombin NEXT (inhibitor OR inhibition) OR direct NEXT thrombin)
in Abstract
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DRAFT FOR CONSULTATION
22
MeSH descriptor Heparin
23
MeSH descriptor Heparin, Low-Molecular-Weight
24
MeSH descriptor Enoxaparin
25
MeSH descriptor Nadroparin
26
MeSH descriptor Dalteparin
27
MeSH descriptor Heparinoids
28
heparin OR heparinoid OR hirudoid OR antixarin OR ardeparin OR bemiparin OR
certoparin OR CY-222 OR dalteparin OR danaparoid OR embolex OR enoxaparin OR
fondaparinux OR fragmin OR idraparinux OR monoembolex OR nadroparin OR
parnaparin OR RD-11885 OR reviparin OR tedelparin OR tinzaparin OR suleparoide
in All Fields
29
MeSH descriptor Warfarin
30
MeSH descriptor Coumarins
31
acenocoumarol OR brodifacoum OR bromadiolone OR cloricromen OR coumafos OR
coumadin OR coumarin OR coumatetralyl OR coumetarol OR dicoumarol OR
difenacoum OR ethyl-biscoumacetate OR flocoumafen OR galbanic-acid OR
nicoumalone OR phenindione OR phenprocoumon OR phepromaron OR tioclomarol
OR sinthrone OR warfarin in All Fields
32
MeSH descriptor Hirudins
33
ximelagatran OR hirudin OR hirudins OR lepirudin OR argatroban OR melagatran OR
aripiprazole OR urokinase OR desirudin OR clopidogrel OR bivalirudin OR efegatran
in All Fields
34
pentasaccharide OR pentasaccharides in All Fields
35
MeSH descriptor Dextrans explode all trees
36
dextran OR dextrans in All Fields
37
MeSH descriptor Aspirin
38
aspirin OR acetylsalicylic NEXT acid in All Fields
39
MeSH descriptor Dipyridamole
40
(clopidogrel OR dipyridamole) in Record Title
41
(clopidogrel OR dipyridamole) in Abstract
42
MeSH descriptor Anesthesia and Analgesia
43
MeSH descriptor Analgesia, Epidural
44
MeSH descriptor Anesthesia
45
MeSH descriptor Anesthesia, Conduction explode all trees
46
anaesthesia OR anesthesia OR anaesthetic* OR anesthetic* OR anaesthetise* OR
anesthetise* OR analgesi* OR spinal OR epidural OR extradural in Record Title
47
anaesthesia OR anesthesia OR anaesthetic* OR anesthetic* OR anaesthetise* OR
anesthetise* OR analgesi* OR spinal OR epidural OR extradural in Abstract
48
MeSH descriptor Early Ambulation
49
MeSH descriptor Motion Therapy, Continuous Passive
50
MeSH descriptor Bed Rest
51
mobili* OR physiotherapy OR ambulation OR kinetic NEXT therapy OR (continuous
OR lateral) NEXT rotation OR (therapeutic OR specialised OR specialized) NEXT bed
OR air NEXT loss NEXT mattress OR bed NEXT rest OR immobili* OR leg NEXT
exercises in Record Title
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DRAFT FOR CONSULTATION
52
mobili* OR physiotherapy OR ambulation OR kinetic NEXT therapy OR (continuous
OR lateral) NEXT rotation OR (therapeutic OR specialised OR specialized) NEXT bed
OR air NEXT loss NEXT mattress OR bed NEXT rest OR immobili* OR leg NEXT
exercises in Abstract
53
MeSH descriptor Hindlimb Suspension
54
(foot OR feet OR limb OR leg OR legs) NEAR (elevat* OR raise* OR suspend*) in
Record Title
55
(foot OR feet OR limb OR leg OR legs) NEAR (elevat* OR raise* OR suspend*) in
Abstract
56
MeSH descriptor Electric Stimulation
57
MeSH descriptor Electric Stimulation Therapy
58
(electric OR electrical OR electrically) NEAR (stimulation OR stimulator OR stimulated
OR stimulate) in Record Title
59
(electric OR electrical OR electrically) NEAR (stimulation OR stimulator OR stimulated
OR stimulate) in Abstract
60
MeSH descriptor Colloids
61
MeSH descriptor Hypertonic Solutions
62
MeSH descriptor Glucose Solution, Hypertonic
63
MeSH descriptor Saline Solution, Hypertonic
64
MeSH descriptor Isotonic Solutions
65
MeSH descriptor Rehydration Solutions
66
MeSH descriptor Water
67
MeSH descriptor Body Water
68
MeSH descriptor Body Fluids
69
MeSH descriptor Water-Electrolyte Balance
70
MeSH descriptor Water-Electrolyte Imbalance
71
MeSH descriptor Dehydration
72
MeSH descriptor Drinking
73
MeSH descriptor Water Deprivation
74
MeSH descriptor Infusions, Intravenous
75
MeSH descriptor Hemodilution
76
MeSH descriptor Sodium Lactate
77
MeSH descriptor Fluid Therapy
78
colloid* OR crystalloid* OR saline OR glucose OR dextrose OR hypertonic OR isotonic
OR (electrolyte NEXT (balance OR imbalance OR disturbance)) OR water OR hydrat*
OR dehydrat* OR rehydrat* OR drink* OR fluid* OR haemodilut* OR hemodilut* OR
(sodium NEXT lactate) OR (lactate NEXT sodium) OR (hartmann NEXT solution) OR
(ringer* NEXT solution) OR (balanced NEXT salt NEXT solution) in Record Title
79
colloid* OR crystalloid* OR saline OR glucose OR dextrose OR hypertonic OR isotonic
OR (electrolyte NEXT (balance OR imbalance OR disturbance)) OR water OR hydrat*
OR dehydrat* OR rehydrat* OR drink* OR fluid* OR haemodilut* OR hemodilut* OR
(sodium NEXT lactate) OR (lactate NEXT sodium) OR (hartmann NEXT solution) OR
(ringer* NEXT solution) OR (balanced NEXT salt NEXT solution) in Abstract
80
#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12
OR #13 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24
OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34
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OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44
OR #45 OR #46 OR #47 OR #48 OR #49 OR #50 OR #51 OR #52 OR #53 OR #54
OR #55 OR #56 OR #57 OR #58 OR #59 OR #60 OR #61 OR #62 OR #63 OR #64
OR #65 OR #66 OR #67 OR #68 OR #69 OR #70 OR #71 OR #72 OR #73 OR #74
OR #75 OR #76 OR #77 OR #78 OR #79
1
2
Patient views search terms
3
Medline
1
Patients.W..DE. OR Inpatients.W..DE. OR Outpatients.W..DE. OR Survivors.W..DE.
2
Caregivers.W..DE. OR Family#.W..DE. OR Parents#.W..DE. OR LegalGuardians#.DE.
3
1 OR 2
4
Anxiety.W..DE. OR Perception.W..DE. OR Body-Image.DE. OR Social-Perception.DE.
OR Attitude.W..DE. OR Attitude-To-Health#.DE. OR Emotions#.W..DE. OR
Depression.W..DE. OR Empathy.W..DE. OR Morale.W..DE. OR Stress.W..DE. OR
Confidentiality.W..DE.
5
Religion#.W..DE. OR Culture#.W..DE.
6
Focus-Groups.DE. OR Questionnaires.W..DE. OR Health-Surveys#.DE. OR HealthCare-Surveys.DE. OR Interviews.W..DE.
7
4 OR 5 OR 6
8
3 AND 7
9
Consumer-Satisfaction#.DE. OR Personal-Satisfaction.DE. OR Patient-AcceptanceOf-Health-Care#.DE. OR Consumer-Participation#.DE. OR Patient-Rights#.DE.
10
Hospital-Patient-Relations.DE. OR Nurse-Patient-Relations.DE. OR Physician-PatientRelations.DE. OR Professional-Patient-Relations.DE.
11
9 OR 10
12
(patient OR patients OR inpatient$ OR outpatient$ OR client$ OR survivor$ OR
consumer OR consumers OR user OR users).TI,AB.
13
(caregiver$ OR care ADJ giver$ OR carer$ OR family OR families OR parent OR
parents OR guardian$).TI,AB.
14
12 OR 13
15
(accept$ OR anxious OR anxiet$ OR attitud$ OR compassion$ OR concern$ OR
confid$ OR cope OR coped OR copes OR coping OR depressed OR depression OR
emot$ OR empath$ OR experienc$ OR fear$ OR feeling$ OR issue OR issues OR
journey$ OR morale OR opinion$ OR participat$ OR perceiv$ OR percept$ OR
perspective$ OR prefer$ OR right OR rights OR satisf$ OR stress OR stressed OR
uncertain$ OR view$ OR worri$ OR worry).TI,AB.
16
(quality NEXT life OR self ADJ esteem OR body ADJ image).TI,AB.
17
(culture OR custom$ OR ethnic$ OR faith$ OR religio$ OR spiritual$ OR belief$ OR
believ$).TI,AB.
18
(focus ADJ (group OR groups) OR observational ADJ (method OR methods) OR
questionnaire OR questionnaires OR survey OR surveys OR interview$).TI,AB.
19
15 OR 16 OR 17 OR 18
20
14 WITH 19
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21
8 OR 11 OR 20
1
2
Embase
1
Patient#.W..DE. OR Consumer.W..DE.
2
Caregiver.W..DE. OR Family.W..DE. OR Parent#.W..DE. OR Custody.W..DE.
3
1 OR 2
4
Anxiety.W..DE. OR Perception.W..DE. OR Attitude.W..DE. OR Emotion#.W..DE. OR
Depression#.W..DE. OR Empathy.W..DE. OR Stress#.W..DE. OR AdaptiveBehavior.DE. OR Body-Image.DE. OR Coping-Behavior.DE. OR
Confidentiality.W..DE. OR Trust.W..DE.
5
Religion.W..DE. OR Cultural-Anthropology.DE.
6
Questionnaire.W..DE. OR Health-Survey.DE. OR Interview.W..DE.
19
4 OR 5 OR 6
8
3 AND 19
9
Patient-Attitude#.DE.
10
Doctor-Patient-Relation.DE. OR Nurse-Patient-Relationship.DE.
11
9 OR 10
12
(patient OR patients OR inpatient$ OR outpatient$ OR client$ OR survivor$ OR
consumer OR consumers OR user OR users).TI,AB.
13
(caregiver$ OR care ADJ giver$ OR carer$ OR family OR families OR parent OR
parents OR guardian$).TI,AB.
14
12 OR 13
15
(accept$ OR anxious OR anxiet$ OR attitud$ OR compassion$ OR concern$ OR
confid$ OR cope OR coped OR copes OR coping OR depressed OR depression OR
emot$ OR empath$ OR experienc$ OR fear$ OR feeling$ OR issue OR issues OR
journey$ OR morale OR opinion$ OR participat$ OR perceiv$ OR percept$ OR
perspective$ OR prefer$ OR right OR rights OR satisf$ OR stress OR stressed OR
uncertain$ OR view$ OR worri$ OR worry).TI,AB.
16
(quality NEXT life OR self ADJ esteem OR body ADJ image).TI,AB.
17
(culture OR custom$ OR ethnic$ OR faith$ OR religio$ OR spiritual$ OR belief$ OR
believ$).TI,AB.
18
(focus ADJ (group OR groups) OR observational ADJ (method OR methods) OR
questionnaire OR questionnaires OR survey OR surveys OR interview$).TI,AB.
19
15 OR 16 OR 17 OR 18
20
14 WITH 19
21
8 OR 11 OR 20
3
4
Cinahl
1
2
3
4
Patient#.W..DE. OR Consumer.W..DE.
Caregivers.W..DE. OR Family#.W..DE. OR Parents#.W..DE. OR GuardianshipLegal.DE.
1 OR 2
Anxiety.W..DE. OR Perception.W..DE. OR Body-Image#.DE. OR Attitude.W..DE. OR
Attitude-To-Health#.DE. OR Attitude-To-Illness.DE. OR Uncertainty.W..DE. OR
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DRAFT FOR CONSULTATION
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
Emotions#.W..DE. OR Depression#.W..DE. OR Empathy.W..DE. OR Morale.W..DE.
OR Stress#.W..DE. OR Privacy-and-Confidentiality.DE.
Religion-and-Religions#.DE. OR Culture#.W..DE.
Focus-Groups.DE. OR Questionnaires#.W..DE. OR Surveys.W..DE. OR
Interviews#.W..DE.
4 OR 5 OR 6
3 AND 7
Personal-Satisfaction.DE. OR Patient-Attitudes.DE. OR Patient-Autonomy.DE. OR
Decision-Making-Patient.DE. OR Patient-Access-To-Records.DE. OR PatientRights#.DE.
Professional-Patient-Relations.DE. OR Physician-Patient-Relations.DE. OR NursePatient-Relations.DE.
9 OR 10
(patient OR patients OR inpatient$ OR outpatient$ OR client$ OR survivor$ OR
consumer OR consumers OR user OR users).TI,AB.
(caregiver$ OR care ADJ giver$ OR carer$ OR family OR families OR parent OR
parents OR guardian$).TI,AB.
12 OR 13
(accept$ OR anxious OR anxiet$ OR attitud$ OR compassion$ OR concern$ OR
confid$ OR cope OR coped OR copes OR coping OR depressed OR depression OR
emot$ OR empath$ OR experienc$ OR fear$ OR feeling$ OR issue OR issues OR
journey$ OR morale OR opinion$ OR participat$ OR perceiv$ OR percept$ OR
perspective$ OR prefer$ OR right OR rights OR satisf$ OR stress OR stressed OR
uncertain$ OR view$ OR worri$ OR worry).TI,AB.
(quality NEXT life OR self ADJ esteem OR body ADJ image).TI,AB.
(culture OR custom$ OR ethnic$ OR faith$ OR religio$ OR spiritual$ OR belief$ OR
believ$).TI,AB.
(focus ADJ (group OR groups) OR observational ADJ (method OR methods) OR
questionnaire OR questionnaires OR survey OR surveys OR interview$).TI,AB.
15 OR 16 OR 17 OR 18
14 WITH 19
8 OR 11 OR 20
1
2
Patient Information and education search terms
3
Medline
1
Patients.W..DE. OR Inpatients.W..DE. OR Outpatients.W..DE. OR Survivors.W..DE.
2
Caregivers.W..DE. OR Family#.W..DE. OR Parents#.W..DE. OR LegalGuardians#.DE.
3
1 OR 2
4
Popular-Works-Publication-Type.DE. OR Information-Services#.DE. OR
Publications.W..DE. OR Books.W..DE. OR Pamphlets.W..DE. OR Counseling.W..DE.
OR Directive-Counseling.DE.
5
3 AND 4
6
((patient OR patients) WITH (education OR educate OR educating OR information OR
literature OR leaflet$ OR booklet$ OR pamphlet$)).TI,AB.
7
Patient-Education.DE. OR Patient-Education-Handout-Publication-Type.DE.
8
5 OR 6 OR 7
4
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1
Embase
1
Patient#.W..DE. OR Consumer.W..DE.
2
Caregiver.W..DE. OR Family.W..DE. OR Parent#.W..DE. OR Custody.W..DE.
3
1 OR 2
4
Information.W..DE. OR Medical-Information.DE. OR Publication.W..DE. OR
Book.W..DE. OR Counseling.W..DE.
5
3 AND 4
6
((patient OR patients) WITH (education OR educate OR educating OR information OR
literature OR leaflet$ OR booklet$ OR pamphlet$)).TI,AB.
7
Consumer-Health-Information.DE. OR Patient-Information.DE. OR PatientEducation.DE. OR Patient-Counseling.DE. OR Patient-Guidance.DE.
8
5 OR 6 OR 7
2
3
4
Cinahl
1
Patient#.W..DE. OR Consumer.W..DE.
2
Caregivers.W..DE. OR Family#.W..DE. OR Parents#.W..DE. OR GuardianshipLegal.DE.
3
1 OR 2
4
Health-Information.DE. OR Print-Materials.DE. OR Literature.W..DE. OR
Pamphlets.W..DE. OR Drug-Information.DE. OR Audiovisuals#.W..DE. OR ElectronicPublications.DE. OR Books.W..DE. OR Counseling.W..DE.
5
3 AND 4
6
((patient OR patients) WITH (education OR educate OR educating OR information OR
literature OR leaflet$ OR booklet$ OR pamphlet$)).TI,AB.
7
Consumer-Health-Information.DE. OR Patient-Education.DE.
50
5 OR 6 OR 7
HEED (Health Economic Evaluations Database) search terms
1
AX='venous thromboembolism' OR AX='vein thromboembolism' OR AX='venous
thrombosis' OR AX='vein thrombosis' OR AX='venous thrombus' OR AX='vein
thrombus' OR AX=dvt OR AX=vte OR AX=thrombophlebitis
2
AX='pulmonary embolism' OR AX='pulmonary emboli' OR AX='lung embolism' OR
AX='lung emboli'
3
TE='Applied Study' OR TE='Review of Applied Studies'
4
CS = (1 OR 2) AND 3
5
AX=surgical OR AX=surgery OR AX=neurosurgery OR AX=neurosurgical OR
AX=operation OR AX=operations OR AX=preoperative OR AX=pre-operative OR
AX=perioperative OR AX=peri-operative OR AX=postoperative OR AX=post-operative
OR AX=orthopaedic* OR AX=orthopedic*
6
AX=resect* OR AX=replacement* OR AX=excision* OR AX=arthroplasty
7
CS = 4 AND (5 OR 6)
5
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APPENDIX D
1
2
Evidence tables
3
4
5
6
Each evidence table is ordered with systematic reviews first then the other
7
studies in alphabetical order.
8
List of tables
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
EVIDENCE TABLE 1: SURGICAL RISK OF VTE: INCIDENCE STUDIES .................................................................. 246
EVIDENCE TABLE 2: PATIENT RISK FACTORS - AGE.......................................................................................... 252
EVIDENCE TABLE 3: PATIENT RISK FACTORS - OBESITY .................................................................................. 253
EVIDENCE TABLE 4: PATIENT RISK FACTORS – HISTORY OF VTE ................................................................... 255
EVIDENCE TABLE 5: PATIENT RISK FACTORS - THROMBOPHILIAS .................................................................... 256
EVIDENCE TABLE 6: PATIENT RISK FACTORS – VARICOSE VEINS..................................................................... 259
EVIDENCE TABLE 7: PATIENT RISK FACTORS – CARDIOVASCULAR FACTORS .................................................. 260
EVIDENCE TABLE 8: PATIENT RISK FACTORS – ORAL CONTRCEPTIVES ........................................................... 262
EVIDENCE TABLE 9: PATIENT RISK FACTORS – HORMONE REPLACEMENT THERAPY ...................................... 264
EVIDENCE TABLE 10: PATIENT RISK FACTORS – CANCER ................................................................................ 266
EVIDENCE TABLE 11: PATIENT RISK FACTORS – CHEMOTHERAPY .................................................................. 267
EVIDENCE TABLE 12: PATIENT RISK FACTORS – PROLONGED TRAVEL ............................................................ 268
EVIDENCE TABLE 13: GRADUATED COMPRESSION STOCKINGS V NO PROPHYLAXIS ........................................ 269
EVIDENCE TABLE 14: IPC DEVICES V NO PROPHYLAXIS ................................................................................... 270
EVIDENCE TABLE 15: FOOT PUMP V NO PROPHYLAXIS ..................................................................................... 271
EVIDENCE TABLE 16: GRADUATED COMPRESSION STOCKINGS ADJUVANT ...................................................... 272
EVIDENCE TABLE 17: IPC DEVICES ADJUVANT ................................................................................................. 273
EVIDENCE TABLE 18: FOOT PUMP ADJUVANT ................................................................................................... 279
EVIDENCE TABLE 19: GRADUATED COMPRESSION STOCKINGS – ABOVE-KNEE V BELOW KNEE ..................... 282
EVIDENCE TABLE 20: IPC – THIGH-LENGTH VERSUS CALF-LENGTH ................................................................. 284
EVIDENCE TABLE 21: MECHANICAL V MECHANICAL .......................................................................................... 285
EVIDENCE TABLE 22: ELECTRICAL STIMULATION V NO PROPHYLAXIS .............................................................. 294
EVIDENCE TABLE 23: PATIENT VIEWS ON MECHANICAL PROPHYLAXIS ............................................................. 296
EVIDENCE TABLE 24: ORAL ANTICOAGULANTS V NO PROPHYLAXIS ................................................................. 301
EVIDENCE TABLE 25: ORAL ANTICOAGULANTS ADJUVANT................................................................................ 303
EVIDENCE TABLE 26: ORAL ANTICOAGULANTS – ADJUSTED VS FIXED DOSE ................................................... 304
EVIDENCE TABLE 27: ORAL ANTICOAGULANTS TIMING ..................................................................................... 306
EVIDENCE TABLE 28: ORAL ANTICOAGULANTS DURATION ................................................................................ 308
EVIDENCE TABLE 29: ORAL ANTICOAGULANTS V UNFRACTIONATED HEPARIN ................................................. 310
EVIDENCE TABLE 30: ORAL ANTICOAGULANTS V LOW MOLECULAR WEIGHT HEPARIN ..................................... 313
EVIDENCE TABLE 31: ORAL ANTICOAGULANTS V ASPIRIN................................................................................. 315
EVIDENCE TABLE 32: ORAL ANTICOAGULANTS V DEXTRAN .............................................................................. 320
EVIDENCE TABLE 33: ORAL ANTICOAGULANTS V HEPARINOIDS ....................................................................... 323
EVIDENCE TABLE 34: DANAPAROID VS NO PROPHYLAXIS ................................................................................. 324
EVIDENCE TABLE 35: DANAPAROID VS DEXTRAN .............................................................................................. 325
EVIDENCE TABLE 36: DANAPAROID VS LOW MOLECULAR WEIGHT HEPARIN .................................................... 327
EVIDENCE TABLE 37: DANAPAROID VS UNFRACTIONATED HEPARIN ................................................................. 329
EVIDENCE TABLE 38: DANAPAROID VS ASPIRIN ................................................................................................ 333
EVIDENCE TABLE 39: DEXTRAN V NO PROPHYLAXIS ......................................................................................... 335
EVIDENCE TABLE 40: DEXTRAN AS AN ADJUVANT ............................................................................................. 338
EVIDENCE TABLE 41: DEXTRAN V LOW MOLECULAR WEIGHT HEPARIN ............................................................ 339
EVIDENCE TABLE 42: DEXTRAN V UNFRACTIONATED HEPARIN......................................................................... 340
EVIDENCE TABLE 43: DEXTRAN V ASPIRIN ........................................................................................................ 344
EVIDENCE TABLE 44: UNFRACTIONATED HEPARIN (UFH) V NO PROPHYLAXIS ............................................... 345
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1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
EVIDENCE TABLE 45:
EVIDENCE TABLE 46:
EVIDENCE TABLE 47:
EVIDENCE TABLE 48:
EVIDENCE TABLE 49:
EVIDENCE TABLE 50:
EVIDENCE TABLE 51:
EVIDENCE TABLE 52:
EVIDENCE TABLE 53:
EVIDENCE TABLE 54:
EVIDENCE TABLE 55:
EVIDENCE TABLE 56:
EVIDENCE TABLE 57:
EVIDENCE TABLE 58:
EVIDENCE TABLE 59:
EVIDENCE TABLE 60:
EVIDENCE TABLE 61:
EVIDENCE TABLE 62:
EVIDENCE TABLE 63:
EVIDENCE TABLE 64:
EVIDENCE TABLE 65:
UFH - DOSE .................................................................................................................... 351
LOW MOLECULAR WEIGHT HEPARIN (LMWH) V NO PROPHYLAXIS .............................. 352
LMWH TIMING: PRE-OP VERSUS POST-OP INITIATION .................................................. 358
LMWH STUDIES COMPARING DOSE ............................................................................... 360
HEPARIN – EXTENDED DURATION ................................................................................... 369
LMWH V UFH ................................................................................................................ 376
PATIENT VIEWS ON HEPARIN ........................................................................................... 393
FONDAPARINUX V LMWH............................................................................................... 396
FONDAPARINUX EXTENDED DURATION ........................................................................... 406
ANTIPLATELET THERAPY VS NO PROPHYLAXIS ............................................................... 408
ASPIRIN ADJUVANT.......................................................................................................... 409
ASPIRIN DOSE ................................................................................................................. 416
ASPIRIN V UNFRACTIONATED HEPARIN ........................................................................... 417
MECHANICAL V PHARMACOLOGICAL PROPHYLAXIS ....................................................... 423
PATIENT VIEWS ON MECHANICAL V PHARMOCOLOGICAL ................................................ 451
REGIONAL V GENERAL ANAESTHESIA ............................................................................. 452
REGIONAL + GENERAL V GENERAL ANAESTHESIA .......................................................... 457
FOOT ELEVATION ............................................................................................................ 458
HYDRATION ..................................................................................................................... 459
VENA CAVAL FILTERS VS NO FILTERS ............................................................................. 460
ECONOMIC EVIDENCE TABLES ........................................................................................ 463
22
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1
Abbreviations used in these evidence tables
BMI
Body mass index
CT
Computed tomography
DVT
Deep vein thrombosis
FU
FUT
Follow-up
125
I-Fibrinogen uptake test
GDC
Graduated compression device
HRQL
Health related qualitty of life
HRT
Hormone replacement therapy
IBS
Irritable bowel syndrome
IPCD
Intermittent pneumatic compression device
LDUH
Low density unfractionated heparin
LE
Life expectancy
LMWH
Low molecular weight heparin
LoS
Length of stay (in hospital)
MI
Myocardial infarction
MRI
Magnetic resonance imaging
NA
Not available
NR
Not reported
OAC
Oral anticoagulant
PE
Pulmonary embolism
PTS
Post-thrombotic limb syndrome
PVT
Proximal vein thrombosis
QoL
Quality of life
RCT
Randomised controlled trial
UFH
Unfractionated heparin
US
Ultrasound
VTE
Venous thromboembolism
V/Q
Ventilation and Quantitative Scan
2
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Evidence Table 1: Surgical risk of VTE: incidence studies
Paper
Andtbacka et
18
al, 2006
Asymptomatic DVT
Not reported
Symptomatic VTE
within 60 days:
Fatal PE
PE
Type of prophylaxis
Type of Surgery
No deaths.
3/3898 (0.07%)
No prophylaxis:
General
(breast cancer)
3898 breast cancer patients.
4416 operations.
Length of operation given as a risk
factor, result broken down using this.
N/A Study draws correlation between
operation length and development of
VTE.
Mean operative time (in patients dev
VTE) = 278 mins
Mean operative time (no VTE) = 256
P = 0.7
No deaths.
2/180 (1.1%)
(Exact one-tailed
95% upper CL
4.8%)
Intraoperative:
antiembolism stocking
plus compression
device.
Post operative:
bilateral mechanical
prophylaxis
(compression
stockings)
Neurosurgery:
Craniotomy and
motor mapping
for glioma
180 patients – all diagnosed with
glioma, no history of DVT.
Mean operation length given as 7.7 hrs,
further info in paper.
7/3898 (0.16%) VTE
3/3898 (0.07%) DVT
only
Auguste et
23
al, 2003
6/180 (3.3%) (Exact
one-tailed 95% upper
CL 6.5%) developed
VTE.
6/180 (3.3%) (Exact
one-tailed 95% upper
CL 6.5%) developed
VTE.
Notes
Of these:
3 (1.7% exact one-tailed
95% upper CL 4%)
developed contralateral
DVT
1 (0.6% exact one-tailed
95% upper CL 2%)
developed ipsilateral
DVT
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Wilcox test demonstrated no
significance between clinical VTE and
age, duration of surgery, preoperative
values for prothrombin time and partial
thromboplastin time.
Obesity, BMI, smoking not included in
analysis.
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Surgical risk of VTE: incidence studies
Paper
Bjornara et
61
al, 2006
Asymptomatic DVT
Not reported
Symptomatic VTE
Fatal PE
Total:
150/5607 (2.7%, CI
2.2-3.1)
Confirmed DVT:
Hip fracture surgery:
36/2420 (1.5%) CI 1.0
to 2.1
THR:
39/2512 (1.6%) CI 1.1
to 2.1
TKR:
11/675 (1.6%) CI 0.82.9
TOTAL:
1.5% (95%CI 2.2-3.1)
Fletcher and
Batiste,
157
1997
14/121 (9.8%) DVT
incidence
PE
Type of prophylaxis
Type of Surgery
Hip fracture
surgery:
32/2420 (1.3%) CI
0.9 -1.9
THR:
28/2512 (1.1%, CI
0.7-1.9)
TKR:
4/675 (0.6% CI 0.21.5)
TOTAL:
1.1% (95%CI 0.91.4)
Thromboprophylaxis
LMWH for approx ten
days or until
discharge.
Subcutaneous
dalteparin (5000 IU)
or enoxaparin (40 mg)
12 hours
preoperatively.
Orthopaedic
Control:
9/32 (28%)
Intervention:
9/30 (30%)
Not significant.
All patients undergoing major hip and
knee surgery who were diagnosed with
objectively confirmed VTE within 6
months of surgery.
Broken down by time of diagnosis
(during initial hospitalisation/after
discharge)
Also broken down by type of surgery.
7 patients developd
DVT and PE
0.1%, 95% CI 0.90.2
Not reported
Not reported
1/121 (0.7%)
5000 unit of
unfractionated
heparin 3x daily,
preoperative-mobile,
and intraoperative
sequential
compression devices.
Vascular
Repair of
abdominal aortic
aneurysm,
reconstruction of
lower extremity
arterial occlusive
disease or
amputation.
Major bleeding 3/121
Not reported
1 fatality in
control from MI
Control:
1/32 (3%)
Intervention:
2/30 (6%)
6g EACA in the
intervention group 5
hours preoperatively.
Urology
(prostatectomy)
RCT: 32 control, 30 int., 50yrs+
9.1% incidence for
reconstructive surgery
14.3% for amputation.
GordonSmith et al,
191
1972
Notes
1 fatality in
control from PE
1/30 (3.3%)
Not significant.
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DRAFT FOR CONSULTATION
Surgical risk of VTE: incidence studies
Paper
Joffe, 1975
Asymptomatic DVT
258
10/23 (43%)
postoperative DVT
Symptomatic VTE
Fatal PE
1/23 (4%) developed
symptomatic DVT
Not reported
PE
None
Type of prophylaxis
Type of Surgery
No prophylaxis
reported
Neurosurgery
Breakdown:
6/10 (60%) of spinal
operations developed
DVT
25/705 (3.5%)
asymptomatic week
after surgery
23 patients.
Age, sex, length of hospital stay given
as not affecting results. Obesity and
previous DVT history as risk factors.
Study aims to compare screening
techniques: Doppler/ I fibrinogen.
No conclusions drawn about efficacy of
screening technique or prophylaxis
4/13 (38%) of
craniotomy operations
(p<0.2)
Keeney et al,
279
2006
Notes
Not reported
Not reported
1/705 nonfatal PE.
(0.1% )
Pneumatic
compression,
adjusted dose
warfarin (7 days),
early mobilisation.
Orthopaedic
(elective hip)
Increased age (p=0.008), male sex
(p=0.005), DVT history (p=0/0005)
identified as risk factors significantly
associated with DVT.
Not reported
Not reported
Cancer patients:
21/507 (4.1%)
Prophylaxis with
intermittent
compression and
early mobilisation,
preoperatively
extending through
discharge.
Major abdominal
surggery in
Gynaecological
oncology
1373 surgery patients, 839 (507 cancer
diagnosis, 332 benign) major abdominal
surgery cases, 534 minor abdominal
surgery cases
Of whom 17/25 (68%)
had proximal DVT.
5/705 (0.7%) presented
with pain within 3
months, all proximal
DVT.
4.2% Total of which:
1.1% distal
3.1% proximal
Martino et al,
346
2006
Not reported
Benign patients:
1/332 (0.3%)
p<0.001 95% CI
1.9-102.1
minor/nonabdominal surgery:
2/536 (0.4%)
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Cancer, age of 60+ identified as risk
factors (p = 0.009 95%CI)
Data also given on different types of
oncological surgery.
DRAFT FOR CONSULTATION
Surgical risk of VTE: incidence studies
Paper
Mayo et al,
351
1971
Asymptomatic DVT
Open prostatectomy
21/41 (51%)
Transurethral resection
2/20 (10%)
Symptomatic VTE
Fatal PE
PE
Not reported
Type of prophylaxis
Type of Surgery
Notes
6g EACA in first 12
hours postoperatively
Urology
(prostatectomy)
61 patients.
Operation type, length, age, bedrest,
blood given all entered into analyses as
risk factors. See p 741.
Various
Incidence broken
down by surgery
type.
12805 operations Number of patients
not given.
Discussion of development of riskcategorisation for patients.
Total: 32/61 (38%)
0.001<p<0.01
Moreano et
372
al, 1998
Total: 34/12805 (0.3%)
DVT: 0.03% (general
otolaryngology)
6% ( in patients with low
dose heparin)
Not reported
General otolaryngology
(GO) 3/4563 (0.1%)
Head and Neck (H&N)
21/3463 (0.6%)
Otology/Neurology (O/N)
8/2526 (0.3%)
Trauma and Plastic
Surgery (T/P) 2/2254
(0.1%)
Phillips et al,
405
2003
Not reported
Not reported
0.02% (general
otolaryngology)
Total: 24/12805
(0.2%)
In the 34 patients
who developed DVT:
0.21% (in
patients with low
dose heparin)
0.52% (in patients
with low dose
heparin)
No prophylaxis: 12
(34%)
Prophylaxis: 22 (65%)
H&N 0.06%
GO 2/4563 (0.04%)
H&N 14/3463
(0.4%)
O/N 6/2526 (0.2%)
T/P 2/2254 (0.1%)
Of which:
11 (32%) preoperative
compression device
2 (6%) postoperative
compression device
9 (26%) stockings
only.
Not reported
0.9% within 3
months
No prophylaxis
reported
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Effectiveness
data on GO
group by type of
prophylaxis.
Orthopaedic
(elective hip)
Medicare records for total hip
replacements for one year
(retrospective study)
71477 patients. Incidence for various
time periods given, calculated as
number of events per 10, 000 personweeks
Broken down by weeks and also
compares primary with revision hip
replacements.
DRAFT FOR CONSULTATION
Surgical risk of VTE: incidence studies
Paper
Asymptomatic DVT
Symptomatic VTE
Fatal PE
PE
Type of prophylaxis
Type of Surgery
Notes
Saarinen et
438
al, 1995
Not reported
Not reported
Not reported
34/7533 (0.45%)
postoperative DVT
(21 Male, 13
female, mean age
63)
Not reported.
Vascular
FINNVASC (Finnish vascular registry)
data.
Breaks down incidence by risk factor
see p 127, e.g. hyperlipidaemia,
smoking, etc. Compares DVT patients
with non-DVT patients for distribution of
vascular operations and risk.
94% of PEs had undergone vascular
procedure involving infrarenal aorta or
lower extremity.
Sinclair et al,
470
1976
No significant difference
between groups.
Not reported
Not reported
Not reported
EACA in the
intervention group,
0.5g per hour for
twelve hours, then 6g
twice daily for ten
days.
Urology
(Elective retropubic
prostatectomy)
Double blind RCT to assess
effectiveness of EACA.
Incidence broken down by intervention
groups and also by type of surgery.
I-fibrinogen test used to identify DVT.
Not reported
Not reported
Not reported
No prophylaxis
reported
Neurosurgery
(major cranial or
spinal
operations)
100 patients undergoing major cranial
or spinal operations.
Broken down by specific type of
surgery, and also by risk factor, e.g.
age,.“leg weakness”, length of op, given
as particular risk factors
20/40 (50%) evidence of
DVT
of which:
13/19 (68%) of
prostatectomy patients
developed DVT
7/21 (33%) of
transurethral resections
Valladares
and
Hankinson,
514
1980
29/100 (29%) developed
DVT
Of whom: 16/36 (44%)
of those with known risk
factors developed DVT.
Of those without risk
factors, 13/64 (20.3%)
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250 of 648
DRAFT FOR CONSULTATION
Surgical risk of VTE: incidence studies
Paper
Warwick et
538
al, 1995
Asymptomatic DVT
Not reported
Symptomatic VTE
Overall
venographically
proven DVT rate
22/1162 (1.89%, CI
1.11-2.76)
Fatal PE
4/1162 (0.34%)
CI 0.09-0.88
PE
14/1162 (1.20%, CI
0.657 to 2.02)
Type of prophylaxis
Type of Surgery
Standard practice:
stockings and early
mobilisation,
Anticoagulant
prophylaxis was not
used routinely but
reserved for those
considered to be at
the greatest risk of
thromboembolism.
Orthopaedic
Notes
Review of records of 1112 patients who
had 1162 primary or revision THR
Total early morbidity from VTE 3.4%
In-patient, all cause mortality rate of
0.86% (10/1162)
90-day mortality rate 1.3% (1.1%,
15/1162)
Total thromboembolitic morbidity : 3.4%
(95%, CI 2.5%-4.7%)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
251 of 648
DRAFT FOR CONSULTATION
Evidence Table 2: Patient Risk Factors - age
Bibliographic
reference
Edmonds et al,
138
2004
Study
Type
Evidenc
e level
Systematic
review
2+
6
cohort
studies
No. of
patients
1927
Patients
characteristics
Exposure
Patients undergoing Age
general,
Different age bands used for different
gynaecological,
studies
elective hip
replacement and 1
study did not specify
the type of surgery.
Other inclusion
criteria:
2 studies - >40 yrs
1 study – 40-80 yrs
3 studies – no other
specific patient
group
Length of
follow up/
exposure
Varied 6 to
8
postoperati
ve
days or for
duration of
hospitalisation
Outcome
measures
Effect size
40 to 60 year olds
Percentage of
24.4%
population with
postoperative DVT 61 to 80 year olds
45.7%
significant
(1 study)
Under 60 year olds
Percentage of
19%
population with
postoperative DVT Over 60 year olds
36%
p<0.0005
(1 study)
Mean +SD age
(years) groups
with and without
postoperative DVT
With DVT 58 +3
Without DVT: 44 +2
Significant
(1 study)
Mean +SD age
(years) groups
with and without
postoperative DVT
With DVT 71.7 +9.8
Without DVT: 59.5
+10.8
Significant
(1 study)
Incidence of
postoperative
DVT. (continuous
range of age)
Constant risk below
45 years, increases
with each year older
(1 study)
Risk estimate for
Odds ratio: 1.21
postoperative DVT CI: 1.04 to 1.42
(1 study)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
252 of 648
Comments
Pooled risk
estimate not
possible because of
different
categorisation of
age
3 studies had
reported no
prophylaxis used, 3
studies did not
report the
prophylaxis used, 1
study did not
control for
prophylaxis.
Diagnosis of DVT:
5 studies fibrinogen
uptake test
1 study bilateral
ascending
venography.
DRAFT FOR CONSULTATION
Evidence Table 3: Patient Risk Factors - obesity
Bibliographic
reference
Edmonds et al,
138
2004
Study
Type
Evidenc
e level
Systematic
review
2+
7
cohort
studies
No. of
patients
4804
Patients
characteristics
Patients undergoing
general,
gynaecological,
thoracic,
orthopaedic,
neurological or
urologic surgery.
Exposure
Length of
follow up/
exposure
Varied 6 to
8
Different definitions used to classify obesity postoperati
ve
days or for
duration of
hospitalisation
Obesity
Other inclusion
criteria:
1 study - adults
2 studies - >40 yrs
1 study – 40-80 yrs
3 studies – no other
specific patient
group
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
253 of 648
Outcome
measures
Effect size
Odds ratio: 2.04
Risk estimate for
postoperative DVT CI 1.04 to 4.02
(1 study)
(BMI>30 vs BMI
<30)
Risk estimate for
postoperative DVT
(definition for
obesity not stated)
Relative risk: 1.43
p<0.025 on
univariate analysis
(1 study)
Risk estimate for
postoperative DVT
(weigth height
analysis used,
definition of
obesity not stated)
Relative risk: 1.95
p<0.01
(higher incidence in
overweight patients)
(1 study)
Weight & obesity
(definition not
stated) as a risk
for postoperative
DVT
Increased weight a
risk p=0.02
Obesity significant
risk factor (no data
provided)
(1 study)
Incidence of
postoperative
DVTs (%
overweight for
height used,
definition not
stated)
With DVT: 13 +3%
Without DVT: 5 +1%
Significant
(1 study)
Incidence of
postoperative
DVTs (%
overweight,
definition not
stated)
Non-significant
difference
(1 study)
Comments
Pooled risk
estimate not
possible because of
different ways of
defining obesity.
Diagnosis of DVT:
5 studies fibrinogen
uptake test
1 study bilateral
ascending
venography
1 study Doppler
ultrasound and
clinical diagnosis
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Exposure
Length of
follow up/
exposure
Outcome
measures
Incidence of
postoperative
DVTs (Definition
of obesity not
recorded)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
254 of 648
Effect size
Non-significant
difference
(1 study)
Comments
DRAFT FOR CONSULTATION
Evidence Table 4: Patient Risk Factors – history of VTE
Bibliographic
reference
Edmonds et al,
138
2004
Study
Type
Evidenc
e level
Systematic
review
2+
4
cohort
studies
No. of
patients
1362
Patients
characteristics
Exposure
Patients undergoing History of venous thrombosis
major
gynaecological, nonlower limb elective
surgery. 1 study with
624 patients did not
specify the type of
surgery.
Other inclusion
criteria:
1 study - >40 yrs
3 studies – no other
specific patient
group
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
255 of 648
Length of
follow up/
exposure
Varied: 6
postoperati
ve
days, for
duration of
hospitalisation or
not
specified
Outcome
measures
Effect size
Risk estimate for
Relative risk: 5.18
postoperative DVT CI: 3.16 to 8.49
(3 studies. 1 study
did not provide
enough data)
Comments
Diagnosis of DVT
by fibrinogen
uptake test
DRAFT FOR CONSULTATION
Evidence Table 5: Patient Risk Factors - thrombophilias
Bibliographic
reference
Edmonds et al,
138
2004
Study
Type
Evidenc
e level
Systematic
review
2+
2
cohort
studies
No. of
patients
1125
Patients
characteristics
Patients undergoing
elective hip or knee
replacement
Exposure
Factor VS Leiden (FVL)
Length of
follow up/
exposure
8 to 14
days postoperatively
in 1 study,
3 months in
other study
Other inclusion
criteria:
1 study - 40 -80 yrs
1 study – no other
specific patient
group
Outcome
measures
Risk estimate for
activated protein
C resiistence
(95% cases had
FVL) &
postoperative
DVT.
Effect size
Relative risk: 4.9
CI: 1.1 to 22.1
(1 study)
Risk estimate for
Odds ratio: 3.18
FVL mutation &
CI: 0.99 to 10.2
postoperative DVT (1 study)
Odds ratio: 2.97
Risk estimate for
CI: 1.27 to 6.92
low sensitivity of
(1 study)
FVL to APC &
postoperative DVT
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
256 of 648
Comments
Diagnosis of DVT:
1 study bilateral
ascending
venography
1 study clinical
diagnosis.
DRAFT FOR CONSULTATION
Thrombophilias
Bibliographic
reference
den Heijer et al,
130
2005
den Heijer et al,
130
2005
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Exposure
2+
Syste
matic
review
of 24
studies
:
3 prospectiv
e
21
retrospectiv
e
3765 cases Any population
5297
controls
Excluded studies in
diseased
populations (irritable
bowel syndrome,
systemic lupus
erythematosis or
Behcet's Syndrome)
Raised homocysteine levels
Syste
2+
matic
review
of 53
studies
8364 cases Any population
12,468
controls
Excluded studies in
diseased
populations (irritable
bowel syndrome,
systemic lupus
erythematosis or
Behcet's Syndrome)
MTHFR 677TT geno-type compared to
MTHFR 677CC geno-type
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
257 of 648
Length of
follow up/
exposure
Not
reported
Not
reported
Outcome
measures
Effect size
Comments
Risk estimate for
venous
thrombosis for a
5μmol/L increase
in measured
plasma total
homocysteine
Not reported how
Odds ratio: 1.27
95% CI: 1.01 to 1.59 venous thrombosis
was diagnosed.
(3 prospective
studies)
Risk estimate for
venous
thrombosis for TT
vs CS genotype
for MTHFR
Odds ratio: 1.20
CI: 1.08 to 1.32
(53 studies)
Odds ratio: 1.60
95% CI: 1.10 to 2.34
(21 retrospective
studies)
Not reported how
venous thrombosis
was diagnosed.
DRAFT FOR CONSULTATION
Thrombophilias
Bibliographic
reference
Galli et al,
176
2003
Study
Type
Evidenc
e level
Syste- 2+
matic
review
of 25
studies
No. of
patients
4184
patients
3151
controls
Patients
characteristics
Medical patients
Exposure
Antiphospholipid syndrome - lupus
anticoagulants and/or anticardiolipin
antibodies
11
case–
control,
3
crosssection
-al
2
ambispectiv
e
9 prospectiv
e
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
258 of 648
Length of
follow up/
exposure
Not
reported
Outcome
measures
Effect size
Comments
Thrombosis verified
by computerised
ultrasonography,
venography for
DVT, angiography
or radionuclide lung
scanning for
Odds ratios varied
Risk estimate for
DVT in studies of from 4.09 (recurrent pulmonary
embolism
event) to 16.2 (any
lupus
event)
anticoagulants
Pooled odds ratios
(4 studies)
alone
for studies were
Significant
classified by type of
Risk estimate for
Significant
event (first event,
DVT in studies of association
recurrent or any
anticardiolipin
No value given
event, which means
antibodies (only G (6 studies)
no distinction was
istope measured) Significant
possible between
first and recurrent
events)
4 studies with 8
Risk estimate for
DVT in studies of associations. Only 1
* None of the
IgG anticardiolipin
IgG and/or IgM
studies found
association
anticardiolipin
anticardioplatin to
significant
antibodies
be a significant risk
factor for
thrombosis
Risk estimate for
DVT in studies of
lupus
anticoagulants
and anticardiolipin
antibodies*
Odds ratios varied
from 5.91 (any
event) to 9.4 (first
event)
(5 studies)
Significant
DRAFT FOR CONSULTATION
Evidence Table 6: Patient Risk Factors – varicose veins
Bibliographic
reference
Edmonds et al,
138
2004
Study
Type
Evidenc
e level
Systematic
review
2+
7
cohort
studies
No. of
patients
4804
Patients
characteristics
Patients undergoing
general,
gynaecological,
thoracic,
orthopaedic,
neurological or
urologic surgery.
Exposure
Varied 6 to
8
postoperati
ve
days or for
duration of
hospitalisation
Varicose veins
Other inclusion
criteria:
1 study - adults
2 studies - >40 yrs
1 study - 40 -80 yrs
3 studies – no other
specific patient
group
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up/
exposure
259 of 648
Outcome
measures
Effect size
Relative risk: 2.39
Risk estimate for
postoperative DVT CI: 1.69 to 3.37
(6 studies. (1 study
had no data)
Comments
Diagnosis of DVT:
5 studies fibrinogen
uptake test
1 study bilateral
ascending
venography
1 study Doppler
ultrasound and
clinical diagnosis.
DRAFT FOR CONSULTATION
Evidence Table 7: Patient Risk Factors – cardiovascular factors
Bibliographic
reference
Edmonds et al,
138
2004
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Systematic
review
2+
411
Patients undergoing
major
gynaecological
surgery
Recent myocardial infarction
Until
discharge
Risk estimate for
Relative risk: 2.51
postoperative DVT p=0.10
(1 study)
Diagnosis of DVT
by fibrinogen
uptake test
2+
3288
Patients undergoing
general,
gynaecological,
thoracic,
orthopaedic,
neurological or
urologic surgery.
Hypertension
Up to 14
days or
until
discharge
Risk of
Not significant, no
postoperative DVT data given
(1 study)
Diagnosis of DVT:
1 study fibrinogen
uptake test
1 study Doppler
ultrasound and
clinical diagnosis.
Exposure
Length of
follow up/
exposure
Outcome
measures
Effect size
Comments
1
cohort
study
Edmonds et al,
138
2004
Systematic
review
2
cohort
studies
Risk estimate for
Relative risk: 1.30
postoperative DVT p=0.22
(1 study)
Other inclusion
criteria:
1 study - adults
1 study - no specific
patient group.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
260 of 648
DRAFT FOR CONSULTATION
Cardiovascular factors
Bibliographic
reference
Edmonds et al,
138
2004
Study
Type
Evidenc
e level
Systematic
review
2+
2
cohort
studies
No. of
patients
3288
Patients
characteristics
Patients undergoing
general,
gynaecological,
thoracic,
orthopaedic,
neurological or
urologic surgery.
Exposure
Congestive cardiac failure
Other inclusion
criteria:
1 study - adults
1 study - no specific
patient group.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up/
exposure
Up to 14
days or
until
discharge
Outcome
measures
Effect size
Risk estimate for
Non-lower limb
postoperative DVT surgery Relative
risk: 1.32
Lower limb surgery
Relative risk: 0.42
(1 study, neither
relative risk
significant)
Risk estimate for
Relative risk: 1.33
postoperative DVT p=0.59
(1 study)
261 of 648
Comments
Diagnosis of DVT:
1 study fibrinogen
uptake test
1 study Doppler
ultrasound and
clinical diagnosis.
1 of the studies
showed a
significant
relationship in a
univariate analysis
but not in a
multivariate
analysis, the other
study showed no
difference. The
figures were not
provided.
DRAFT FOR CONSULTATION
Evidence Table 8: Patient Risk Factors – oral contrceptives
Bibliographic
reference
Edmonds et al,
138
2004
Study
Type
Evidenc
e level
Syste- 2+
matic
review
with 2
case
control
studies
and 5
cohort
studies
No. of
patients
Not stated
for all
studies
Patients
characteristics
Patients undergoing
general, elective
gynaecological,
emergency
gynaecological,
thoracic,
orthopaedic,
neurological or
urologic surgery.
Exposure
Oral contraceptives
Non-users of oral contraceptives
Outcome
measures
Effect size
Odds ratio: 2.48
3 days to 3 Risk estimate for
postoperative DVT CI: 1.53 to 4.02
months or
(3 studies)
entire
postoperati
ve hospitalisation
Comments
A pooled risk
estimate was only
possible for three of
the studies due to
deficiencies in
reported data.
Diagnosis of DVT:
3 studies fibrinogen
uptake test
1 study Doppler
ultrasound and
clinical diagnosis
2 studies used
discharge data for
diagnosis of DVT
1 study not
specified
Other inclusion
criteria:
1 study - adults
1 study – 15-44 yrs
2 studies – /16-40
yrs olds
1 study – 40-80 yrs
3 studies – no other
specific patient
group
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up/
exposure
262 of 648
DRAFT FOR CONSULTATION
Oral contraceptives
Bibliographic
reference
Study
Type
Kemmeren et al, Syste281
2001
matic
review
3
cohort
studies
9 casecontrol
studies
3
nested
casecontrol
studies
Evidenc
e level
2+
No. of
patients
Patients
characteristics
1598 cases Current oral
3265
contraceptive users.
controls
Data collected from
Western countries.
Exposure
rd
3 generation oral contraceptives:
desogestral
gestodene
nd
2 generation oral contraceptives
levonorgestrel
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
263 of 648
Length of
follow up/
exposure
Not
reported
Outcome
measures
Effect size
Risk estimate for
venous
rd
thrombosis 3 vs
nd
2 generation
contraceptives
Unadjusted odds
ratio:
1.6 (CI: 1.3 to 1.9)
(4 studies)
Adjusted odds ratio:
1.7 (CI: 1.4 to 2.0)
(3 studies)
Risk estimate for
venous
thrombosis
desogestrel vs
levonorgestrel
Unadjusted odds
ratio:
1.9 (CI: 1.5 to 2.3)
(6 studies)
Adjusted odds ratio:
1.7 (CI: 1.2 to 2.6)
(4 studies)
Risk estimate for
venous
thrombosis
gestodene vs
levonorgestrel
Unadjusted odds
ratio:
1.7 (CI: 1.3 to 2.2)
(5 studies)
Adjusted odds ratio:
1.5 (CI: 1.3 to 2.2)
(3 studies)
Risk estimate for
venous
rd
thrombosis 3 vs
nd
2 generation
(type of
progestagen
unspecified)l
Unadjusted odds
ratio:
1.5 (CI: 1.2 to 1.8)
(4 studies)
Adjusted odds ratio:
1.4 (CI: 1.1 to 1.9)
(3 studies)
Comments
Author reports:
some studies
reported only
frequencies, some
only unadjusted or
adjusted odds
ratios. They
performed an
overall analysis
based on the
adjusted odds
ratios and on the
2x2 tables
separately.
*Diagnosis
confirmed by
ultrasound,
plethysmography or
venography.
Not all studies in
used an objective
test to diagnose
venous thrombosis.
DRAFT FOR CONSULTATION
Evidence Table 9: Patient Risk Factors – hormone replacement therapy
Bibliographic
reference
Miller et al,
363
2002
Study
Type
Evidenc
e level
Systematic
review
2+
12
studies
3
RCTs
1
cohort
8 casecontrol
studies
No. of
patients
RCTs:
3919
Cohort
studies:
476,008
Casecontrol
studies:
22,137
Patients
characteristics
Post-menopausal
women
Exposure
Hormone replacement therapy
Post menopausal oestrogen replacement
Excluded:
women with a
history of thrombotic
events or conditions
associated with high
risk for thrombosis
Women in 1 RCT
were healthy
Women in 2 RCTs
had heart disease
Oestrogen alone or oestrogen plus
progestin
RCTs and the cohort study were outpatient
studies. The RCTs used a placebo for the
control group.
4 case control studies used hospital based
controls
4 case control studies used population
based controls
Health status not
recorded for cohort
or case control
studies
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up/
exposure
Effect size
Not
Risk estimate for
reported for venous
all studies. thromboembolism
Relative risk: 2.14
Cred Int: 1.64 to
2.81
(all studies)
RCTs: one
not
specified,
other two 3
or 4 years.
Risk estimate
venous
thromboembolism
Relative risk: 3.75
Cred Int: 1.23 to
10.26
(3 RCTs)
Risk estimate
venous
thromboembolism
Relative risk: 2.1
Cred Int: 1.2 to 3.8
(1 cohort study)
Risk estimate
venous
thromboembolism
Relative risk: 2.05
Cred Int: 1.40 to
2.95
(8 case control
studies)
Risk estimate
venous
thromboembolism
first year use vs
subsequent years
Relative risk in 1st
year of use: 3.49
Cred Int: 2.33 to
5.59
Relative risk after 1
year of use:: 1.91
Cred Int: 1.18 to
3.52
(6 studies)
Cohort:
compared
>5 year use
with <
5years
Case
controls:
not
reported
264 of 648
Outcome
measures
Comments
Mehtod of
diagnosis for
thromboembolism
diagnosis varied.
Most rigorous
venography,
ultrasonography or
Doppler
ultrasonography for
DVT, venography
or perfusion scan
for PE. 3 studies
did not state the
method of
diagnosis.
Relative risks and
credible intervals
(Cred Int)
calculated using a
bayesian metaanalysis.
DRAFT FOR CONSULTATION
Hormone replacement therapy
Bibliographic
reference
Royal College of
Obstetricians
and
Gynaecologists,
435
2004
Study
Type
Evidenc
e level
2+
Syste
matic
review
including 9
studies
No. of
patients
Not
reported
Patients
characteristics
Exposure
Women on hormone Hormone replacement therapy
replacement therapy (oestrogen)
Exact
inclusion/exclusion
criteria not reported.
No description of the control groups
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
265 of 648
Length of
follow up/
exposure
Not
reported
Outcome
measures
Risk estimates
reported for each
study, no pooled
estimate
Effect size
Relative risks varied
from: 1.22 up to 6.9
Comments
DRAFT FOR CONSULTATION
Evidence Table 10: Patient Risk Factors – cancer
Bibliographic
reference
Edmonds et al,
138
2004
Study
Type
Evidenc
e level
Systematic
review
2+
6
cohort
studies
3
RCTs
No. of
patients
1867
Patients
characteristics
Patients undergoing
general and
gynaecological,
surgery for
malignancy.
Other inclusion
criteria:
5 studies - >40 yrs
3 studies – no other
specific patient
group
1 study included 3
groups – a control,
oral contraceptive
users and cervical
cancer patients
Exposure
Cancer
3 RCTs with 628 participants included
prophylaxis:
1 study - heparin and electical calf
stimulation
1 study – IPC calf stimulation
1 study - GCS
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
266 of 648
Length of
follow up/
exposure
Varied 6 to
7
postoperati
ve
days or for
duration of
hospitalisation
Outcome
measures
Effect size
Risk estimate for Odds ratio: 2.94
postoperative DVT CI: 2.01 to 4.29
(9 studies)
Comments
Diagnosis of
DVTwith fibrinogen
uptake test for all
the studies.
DRAFT FOR CONSULTATION
Evidence Table 11: Patient Risk Factors – chemotherapy
Bibliographic
reference
Study
Type
Braithwaite et al, Syste73
2003
matic
review
32
RCTs
Evidenc
e level
2+
No. of
patients
52, 929
Patients
characteristics
Patients receiving
tamoxifen for
treatment or
prevention of
cancer.
Exposure
Tamoxifen
Compared to no chemotherapy agent
Mean length of years receiving tamoxifen:
4.3 years
Mean age: 54.8
years
4 RCTs – risk
reduction for breast
cancer
25 RCTs – treatment
of breast cancer
3 RCTs - treatment
of metastatic
melanoma
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
267 of 648
Length of
follow up/
exposure
Outcome
measures
Effect size
Varied from Risk estimate for
2.8 to 15
DVT
years
Relative risk: 1.87
CI: 1.33 to 2.66
(15 studies)
Risk estimate for
pulmonary
embolism
Relative risk: 1.88
CI: 1.17 to 3.01
(11 studies)
Comments
Method of
diagnosis for DVT
not reported.
DRAFT FOR CONSULTATION
Evidence Table 12: Patient Risk Factors – prolonged travel
Bibliographic
reference
Aryal and Al22
khaffaf, 2006
Study
Type
Evidenc
e level
Systematic
review
2+
2
cohort
studies
4 prospectiv
e casecontrol
studies
3 incidence
studies
No. of
patients
Cohort
studies:
2497
Case
control
studies:
3084
Incidence
studies:
182.87
million
Patients
characteristics
Air passengers
Exposure
Air travel or long distance travel
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
268 of 648
Length of
follow up/
exposure
Not
reported
Outcome
measures
Effect size
Risk estimate for
VTE for air travel
Odds ratio: 1.59
CI: 1.04 to 2.43
(3 case-control
studies)
Risk estimate for
VTE for air travel
Relative risk: 2.93
CI: 1.58 to 5.58
(2 cohort studies)
Risk estimate for
VTE for any long
distance travel
Odds ratio: 2.6
CI: 1.79 to 3.79
(2 case-control
studies)
Incidence of
symptomatic
pulmonary
embolism after
long haul flights
varied from 0.41 per
million to 2.57 per
million
(3 incidence studies)
Comments
Not all studies
stated method of
diagnosis
DRAFT FOR CONSULTATION
Evidence Table 13: Graduated compression stockings vs no prophylaxis
Bibliographic
reference
Amaragiri and
15
Lees, 2000
7 RCTs
included:
13,237,242,462,505,50
6,510
Study
Type
Evidenc
e level
Systemat 1+
ic Review
No. of
patients
Total:
16 studies,
7 with 1027
participants
Patients
characteristics
General surgery,
orthopaedics,
neurosurgery and
obstetrics and
gynaecology.
Interventio
Age: > 16 years
n: GCS
alone n =
536
Control: no
stockings n
= 491
Intervention
Graduated
compression stockings
(thigh-length 4 studies,
length not stated 2
studies, thigh and
knee-length 1 study)
Comparison
Nil prophylaxis
Additional noncomparative
prophylaxis:
Not reported
Timing: start time
varied from day of
admission to same day
as surgery, end time
varied from 4 to 5 days
to 9 days
postoperatively to day
of discharge.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
269 of 648
Length of
follow up
Not stated
Outcome
measures
DVT Confirmed
by: venogram,
US, isotope
studies
Effect size
Int: 81/536
Control: 144/491
p value: <0.00001
(Significant)
Comments
Not reported: PEs,
type of DVT, side
effects, QoL and
LoS.
DRAFT FOR CONSULTATION
Evidence Table 14: IPC devices vs no prophylaxis
Bibliographic
reference
Study
Type
Evidenc
e level
Roderick et al, Systemat 1+
430
2005
ic Review
17 RCTs
25,63,83,84,97,99,102,
103,155,178,229,243,2
50,472,507,508,541
No. of
patients
Patients
characteristics
Total: 2181 Type of surgery:
Gynaecology: 2
studies
Some
studies do Orthopaedic: 5
studies
not report
General: 4 studies
numbers
Neurosurgery: 5
for each
studies
arm.
Urology: 1 study
Intervention
Comparison
IPCD
Nil prophylaxis
Timing:
Start time varied from
pre-op to time of
anaesthesia to postop.
Additional noncomparative
prophylaxis:
Not reported
End time varied from
17-24 hours to 17 days
postop or until
ambulation or
discharge.
Length of
follow up
Not stated
Outcome
measures
DVT confirmed by Int: 112/989
Doppler US, FUT Cont: 263/1001
p value: 0.0000
or impedence
phlethysomograph
Int: 14/564
PE by
angiography, PE’s Cont: 18/579
identified at post- p value: 0.5924
mortem and no
systematic
assessment of PE
(post-mortem
only)
Proximal DVT
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
270 of 648
Effect size
Int: 45/663
Cont: 85/678
p value: 0.0013
Comments
Not reported:
QoL, major
bleeds, LoS,
PTS.
DRAFT FOR CONSULTATION
Evidence Table 15: Foot pump vs no prophylaxis
Bibliographic
reference
Study
Type
Evidenc
e level
Roderick et al, Systemat 1+
430
2005
ic Review
2 RCTs
included
463,553
No. of
patients
2 studies
Total: 126
Int: 61
Cont: 65
Patients
characteristics
Intervention
Foot pump
Type of surgery:
General:: 1 study
Orthopaedic: 1 study Additional noncomparative
prophylaxis:
Timing:
Not reported
One study was
periop. The other
study was postop to
day 9-10.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Nil
Additional noncomparative
prophylaxis:
Not reported
271 of 648
Length of
follow up
Outcome
measures
One study
on day 9 or
10 post op.
Other study
on day
1,2,3,5,7
ostop.
DVT confirmed by
venography or
FUT
Int: 11/61
Cont: 34/65
p value: 0.0001
PE confirmed by
scan
Int: 0/28
Cont: 0/32
(reported in 1 study)
p value: N/A
Proximal DVT
Int: 0/28
Cont: 6/32
(1 study reported)
p value: 0.0345
Effect size
Comments
Not reported: LoS,
QoL, PTS, and
major bleeds.
DRAFT FOR CONSULTATION
Evidence Table 16: Graduated compression stockings adjuvant
Bibliographic
reference
Amaragiri and
15
Lees, 2000
8 RCTs
included:
32,54,166,395,461,503,
548,549
Study
Type
Evidenc
e level
Systemat 1+
ic review
No. of
patients
Patients
characteristics
General surgery,
Total:
16 studies, orthopaedics and
9 with 1184 medical patients
participants
Study with medical
Interventio patients excluded.
n: GCS
Age: > 16 years
alone n =
589
Intervention
Graduated
compression tockings
(thigh-length for 7
studies, not stated for
2 studies)
Timing:
Started either on day
of admission or day of
operation
Control: no
stockings n
= 595
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
No comparative
prohylaxis
Additional noncomparative
prophylaxis:
Dextran 70 (3
studies),
subcutaneous
heparin (3
studies), aspirin (2
studies),
sequential
compression (1
study)
272 of 648
Length of
follow up
Not stated
Outcome
measures
DVT Confirmed
by: venogram,
US, isotope
studies
Effect size
Int: 18/589
Control: 84/595
p value: <0.00001
(Significant)
Comments
Not reported: PEs,
type of DVT, side
effects, QoL and
LoS.
DRAFT FOR CONSULTATION
Evidence Table 17: IPC devices adjuvant
Bibliographic
reference
Study
Type
Evidenc
e level
Roderick et al, Systemat 1+
430
2005
ic Review
7 RCTs
included:
89,327,432,473,510,53
9
No. of
patients
8 studies (1
excluded:
Pambianco
1995 as
Medical not
surgery)
Patients
characteristics
Type of surgery:
Orthopaedic: 2
studies
Neurosurgery: 3
studies
Mixed: 1 study
General: 1 study
Intervention
IPC & GCS (4 studies)
IPC & Aspirin (1 study)
IPC & Heprin (1 study)
IPC & Dextran (1
study)
Total: 1005
Timing:
Start time varied
from preop to
postop.
End time varied from
postop 3 days to 10
days/ambulant.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
GCS (4 studies)
Aspirin (1 study)
Heprin (1 study)
Dextran (1 study)
Additional noncomparative
prophylaxis:
Not reported
273 of 648
Length of
follow up
Not
reported
Outcome
measures
Effect size
DVT confirmed by
Doppler US,
fibrinogen uptake,
impedance
phlethysmograph
or venography
Int: 39/412
Cont: 54/416
p value: = 0.1234
PE confirmed by
angiography or
scan
Int: 4/188
Cont: 7/176
(reported in 4
studies)
p value: 0.3673
Proximal DVT
Int: 6/282
Cont: 8/277
(reported in 5
studies)
p value: 0.5997
Comments
Notes: Not all
studies report total
number of patients
in each arm of
study.
Not reported:
Major bleeds, QoL,
hospital stay, PTS
DRAFT FOR CONSULTATION
IPC devices adjuvant
Bibliographic
reference
Eskander et
145
al, 1997
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 45
Type of surgery:
Patients with
Interventio fractures of femoral
neck
nn = 21
Control:
Exclusion criteria:
n = 24
history of VTE,
currently taking
aspirin or warfarin,
cancer, dementia.
Intervention
Comparison
Enoxaparin
Intermittent calf
compression garments (dose not
specified)
(Flowtron DVT) then
Enoxaparin (dose not
specified)
Timing
Compression device
started at the time of
admission and
continued for 48 hours
Intervention: Mean after fracture. Then
age: 78.7 (range 41- Enoxaparin given until
postoperative day 7.
91) yrs
M/F: Not reported
Control: Mean age:
80.2 (range 41-90)
yrs
M/F:
Not reported
Timing
Started at the time
of admission and
continued until
postoperative day
7.
Additional noncomparative
prophylaxis:
Not reported
In total population
M/F : 7/38
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
274 of 648
Length of
follow up
Outcome
measures
7 days
postoperati
vely
DVT Confirmed
by: Colour Duplex
Doppler
Int: 2/21
Control: 4/24
p value: >0.05
PE
Confirmed
by: Colour Duplex
Doppler
Int: 1/21
Control: 0/24
p value: 0.1111
Effect size
Comments
Not reported
proximal DVT, fatal
PE, PTS, bleeding
complications, QoL,
survival, LoS
Funding:
not reported
DRAFT FOR CONSULTATION
IPC devices adjuvant
Bibliographic
reference
Goldhaber et
188
al, 1995
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 344
Intervention
: n = 172
Control: n =
172
Patients
characteristics
Type of surgery:
Coronary artery
bypass
Duration
not reported
Intervention
Comparison
Type: Thigh-length
IPC device
Dose: 30-45mm Hg
Graduated
compression
stocking (length
unknown).
Appears to be
begun
immediately postop.
Timing:
Intervention: Mean First 98 patients
started >24 hours
age: 63.2 ± 9.7 yrs
postoperatively
M/F:137/35
Patients 99 to 344
Control: Mean age: begun 4 -12 hrs postsurgery.
X±Y M/F:92/77
Pre-existing risk
factors: Significantly
greater proportion of
patients in the
comparison group
had cancer
Aspirin 325
mg/day (unless
contraindicated)
Appeared to be worn
until discharge
Additional noncomparative
prophylaxis:
Graduated
compression stocking
(length unknown).
Appears to be begun
immediately post-op.
Aspirin 325 mg/day
(unless
contraindicated)
Length of
follow up
Both
groups:
followed up
until
discharge
Outcome
measures
Effect size
DVT Confirmed
by: bilateral
doppler US on or
after 4 post-op
day
Int:
31/164
Control: 36/166
p value: 0.62
Proximal DVT
Confirmed by: As
above
Int: 5/164
Control: 6/166
p value: 0.98
Int: 1/164
PE Not
routinely screened Control: 1/166
p value: 1.0000
for. Non-fatal PE
in control group
confirmed by high
probability V/Q
scan
Fatal PE
Confirmed by:
clinical evaluation
(presumably).
Patient underwent
pulmonary
emobolectomy
procedure so
diagnosis reliable
Int: 1
Control: 0/166
Patient had not
received the
intervention and is
not included in any
other analysis as no
DVT measure had
been obtained.
(therefore 1/165)
Survival
Int: 2/164
Control: 0/166
p value: 0.2462
Length of
Hospital Stay
Int: Median 9
Control: Median 9
p value: 0.36 Not
significant
Comments
Comments: 14
participants
dropped out after
randomisation (8
IPC + GCS; and 6
GCS). First 98
patients enrolled
had delayed
initiation of
prophylaxis
(outcome for these
patients were not
significantly
different). Any
interruption of
prophylaxis > 3hrs
was recorded.
Significantly more
non-compliance in
the IPC group.
Difference between
groups still Not
significant when
analysed with only
those whos
conpliance had not
been interrupted.
Age was a
significant
predictors of DVT
Not reported: PTS,
QoL, bleeding
Funding:
not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
275 of 648
DRAFT FOR CONSULTATION
IPC devices adjuvant
Bibliographic
reference
Study
Type
Killewich et al, RCT
290
2002
Evidenc
e level
1+
No. of
patients
Total: 45
Int1: 13
Int2: 15
Cont: 16
Patients
characteristics
Patients undergoing
major abdominal
surgery (35 bowel &
10 aortic
reconstructions).
Mean age: 67
M/F: 44:1
Intervention
Intervention 1:
IPCD (thigh-length) +
unfractionated heparin
(5000 units)
subcutaneously twice
a day
Timing:
Started with
anaesthesia and
continued until
postoperative day 5 or
discharge.
Intervention 2:
IPCD (thigh-length)
during surgery and for
the first 48 hrs after.
Additional noncomparative
prophylaxis:
Patients undergoing
aortic reconstruction
also given systemic
heparin during surgery
which was reversed at
end with protamine.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Unfractionated
heparin (5000
units)
subcutaneously
twice a day
Timing:
Started with
anaesthesia and
continued until
postoperative day
5 or discharge.
Additional noncomparative
prophylaxis:
Patients
undergoing aortic
reconstruction
also given
systemic heparin
during surgery
which was
reversed at end
with protamine.
276 of 648
Length of
follow up
Outcome
measures
5 days or
until day of
discharge
Proximal DVT
Confirmed by
venous duplex US
scan
Effect size
Int: 1: 0/13
Int 2: 0/15
Control: 0/16
P value: not
significant
Comments
It appears that the
treatment was
different to pts with
aortic
reconstructions.
DVT prophylaxis
was initiated in the
operating room
after induction of
anesthesia and
continued until post
op day 5 or
discharge
Not reported:
PE, PTS, Bleedingrelated
complications, QoL,
Survival
DRAFT FOR CONSULTATION
IPC devices adjuvant
Bibliographic
reference
Larson et al,
309
2001
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 254
Interventio
n: n = 123
Control: n
= 131
Patients
characteristics
Intervention
Aspirin prophylaxis +
Type of surgery:
Knee-high
Total Knee
arthroplastic surgery compression stockings
& Intermittent kneehigh pneumatic
Intervention:
Mean age: 68 (range compression sleeves
(1991-1996)
22-84) yrs
M/F: 31/92
Comparison
Aspirin
prophylaxis alone
(1983-1991)
Additional noncomparative
prophylaxis:
Not reported
Control:
Mean age: 64 (range
30-83 ) yrs
M/F:
39/95
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
277 of 648
Length of
follow up
Scans
performed
a mean 5
days
postoperati
vely (range
4-7 days).
Outcome
measures
Effect size
DVT Confirmed
by: Interventions,
Doppler vein
examinations
Control, Duplex
US
Int: 9/123
Control: 21/131
p value: <0.035
PE
Confirmed
by:
Ventilation/perfusi
on scan or
Pulmonary
angiography
Int: 0/123
Control: 1/131
Bleeding related
complications
(as requiring
additional
trasfusion or
reoperation)
Int: 0/123
Control: 1/131
p value: 1.0000
Comments
Comments: All
patients were given
650 mg of aspirin
the night before the
surgery, and this
dose was continued
twice a day
postoperatively for
6 weeks
Not reported:
Proximal DVT, fatal
PE, PTS, QoL,
survival, LoS
Funding:
DRAFT FOR CONSULTATION
IPC devices adjuvant
Bibliographic
reference
Ramos et al,
421
1996
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 2551
Interventio
n: n = 1355
Control: n
= 1196
Patients
characteristics
Patients who
underwent cardiac
surgery over a 10
year period
Intervention
M/F: 968/387
Mean age: 63±13
Control
M/F: 814/382
Mean age: 65±11
Intervention
Type Thigh-length
IPCD
+ subcutaneous
heparin (5000 units
every 12 hours)
Both started
immediately after
surgery and continued
for 4 to 5 days or until
the patient was
ambulatory.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Type: UFH
Dose: 5,000 U
every 12hrs
Started
immediately after
surgery and
continued for 4 to
5 days or until the
patient was
ambulatory.
Additional noncomparative
prophylaxis:
Not reported
278 of 648
Length of
follow up
Outcome
measures
4 to 5 days
Symptomatic PE
25 were confirmed
by ventilation
perfusion scan, 42
by pulmonary
angiogram and 2
by autopsy
Int: 21/1355
Control: 48/1196
The frequency of
conconmitant use of
bilateral PCS and
SCH reduced the
frequency of post-op
PE in 62% in
comparison to
prophylaxis with
SCH alone
(95% CI, 47.2 to
71.3)
p value: 0.01
Fatal PE
Confirmed by
autopsy
2 (paper does not
report to which
groups they belong)
Study
carried out
during a 10
year period
Effect size
Comments
Patients were
excluded from
either group for
some of the
following reasons:
known DVT prior to
surgery, bleeding
complications,
intra-operative
death, intolerance
to PCS or
withdrawal of
prophylaxis before
full ambulation
Not reported:DVT,
PTS, Bleeding
related
complications, QoL,
Survival
DRAFT FOR CONSULTATION
Evidence Table 18: Foot pump adjuvant
Bibliographic
reference
Stranks et al,
487
1992
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Intervention
Patients undergoing
surgery for fracture
Interventio of the neck of femur
(hemiarthroplasty)
n:n = 41
Foot pump (A-V
impulse system) +
thigh-length graduated
compression stockings
Control: n
= 39
Foot pump started
immediately after the
operation and used for
7 to 10 days while the
patient was in bed or
sitting at rest. Not
stated whether applied
to one or both feet.
Total: 82
Excluded:
Previous history of
VTE, chronic venous
insufficiency,
presence of
malignant tumour.
Intervention:
Mean age: 79.1
M/F: 6/35
Control:
Mean age: 82
M/F: 9/30
Comparison
10 days
Thigh-length
graduated
compression
stockings added
to both legs before
operation and
used for 10 days.
Additional noncomparative
prophylaxis:
Regional
anaesthesia:
11/39
Stockings added to
both legs before
operation and used for
10 days.
Additional noncomparative
prophylaxis:
Regional anaesthesia:
10/41
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
279 of 648
Outcome
measures
Effect size
Proximal DVT
Confirmed
by:doppler US ---
Int: 0/40
Control: 9/39
p value: <0.01
Bleeding related
complications
Int: 0/40
Control: 0/39
p value: Not
significant
Comments
Not reported:
All DVT, PE, fatal
PE, PTS, QoL,
Survival
DRAFT FOR CONSULTATION
Foot pump adjuvant
Bibliographic
reference
Study
Type
Stannard et al, RCT
482
1996
Evidenc
e level
+
No. of
patients
Total: 75
Int 1: 25
Int 2: 25
Control: 25
Patients
characteristics
Intervention
Intervention 1:
Type of surgery:
uncemented total hip Type: Bilateral foot
pump (PlexiPulse) +
arthroplasty
LDUH + aspirin
Dose: FP 16hrs/day
Duration of
for first 3 days, then
surgery:
Int1:
mean 106 (85 - 128) 12hrs/day; LDUH
5000U; Aspirin 325 mg
mins; Int2: mean
113 (15 - 135) mins;
Cont: mean 111 (87 Intervention 2:
Type: Bilateral foot
- 140) mins;
pump 16hrs/day for
first 3 days, then
Intervention 1:
12hrs/day
Mean age: 68.7
(range 48-86) yrs
Timing:
M/F:not reported
FP begun immediately
Intervention 2:
Mean age: 65 (range post-surgery and
51-79) yrs M/F:not continued until end of
study; LDUH begun
reported
12hrs pre surgery and
Control:
every 12hrs for first 3
Mean age: 69.7
days post-surgery,
(range 28-86) yrs
then aspirin 3x daily
M/F:not reported
until end of study
Comparison
Type: LDUH +
aspirin
Dose: LDUH
5000U; Aspirin
325 mg
Timing:
LDUH begun
12hrs pre surgery
and every 12hrs
for first 3 days
post-surgery, then
aspirin 3x daily
until end of study
Additional
prophylaxis:
Spinal
anaesthesia:
21/25
Additional
prophylaxis:
Spinal anaesthesia:
22/25
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
280 of 648
Length of
follow up
2 weeks
postoperati
vely
Outcome
measures
Effect size
DVT Confirmed
by: Duplex US.
Positive scans
confirmed by
venography
Int1: 0/25
Int2: 0/25
Cont: 5/25
p value: = 0.009
(significant)
PE
Confirmed
by: Not routinely
screened for. No
confirmatory tests
reported
Int1: 0/25
Int2: 0/25
Control: 1/25
p value: Not
reported
Bleeding related
complications
Surgical wound
drainage - time
taken for wound to
seal (no of days
post-op)
Int1: 5.9/25
Int2: 3.8/25
Control: 6.2/25
p value: = 0.05
(Significant)
Survival (specify)
Int1: 25/25
Int2: 25/25
Control: 25/25
p value: Not
significant
Comments
3/5 DVTs were
symptomatic. 1 PE
was symptomatic.
4/5 patients who
developed DVT had
spinal anaesthesia.
Two patients
reported as
excluded from
study due to
abnormal pre-op
US findings. Does
not report to which
group(s) they
belonged
Not reported:
LoS, QoL, PTS,
proximal DVT
Funding: Not
reported
DRAFT FOR CONSULTATION
Foot pump adjuvant
Bibliographic
reference
Study
Type
Evidenc
e level
Roderick et al, Systemat 1+
430
2005
ic Review
One RCT
160
included
No. of
patients
Total:
Int 1:
Int 2:
Control:
Patients
characteristics
Intervention
Intervention 1:
Type of surgery:
Orthopaedic surgery Type: Foot pump and
GCS
(Foot of operated leg)
Timing: postoperative
during sitting and bed
rest
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Type: GCS
(Bilateral)
Timing: Started
postoperatively
but not stated
duration.
281 of 648
Length of
follow up
6-9 days
postoperati
vely
Outcome
measures
Effect size
DVT Confirmed
by: venography
Int1: 4/39
Cont 16/40
p value: 0.0038
Proximal DVT:
Int1: 2/39
Control: 13/40
p value: 0.0031
Comments
Not reported: PE,
LoS, QoL, or PTS.
DRAFT FOR CONSULTATION
Evidence Table 19: Graduated compression stockings – Above-knee vs below
knee
Bibliographic
reference
Study
Type
Evidenc
e level
Roderick et al, Systemat 1+
430
ic Review
2005
with 2
RCTs
2 RCTs
included
414,550
No. of
patients
Total: 212
Interventio
n Aboveknee
stockings
n = 104
Patients
characteristics
Adults having
general surgery.
Intervention
Above-knee stockings
Timing:
One study reports DVT
assessment from
postop to discharge
and other study has
not stated timing.
Comparison
Below knee
stockings.
Additional noncomparative
prophylaxis:
Not reported
Control:
Below knee
stockings
n = 108
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
282 of 648
Length of
follow up
Outcome
measures
DVT confirmed by:
DVT
assessed in fibrinogen uptake
one study
at postopdischarge
(alternate).
The other
study does
not report
follow-up.
Effect size
Int: 9/100
Cont: 9/102
p value: 1.0000
Not significant
Comments
Not reported:
proximal DVT, PE,
PTS, bleeding, QoL
and LoS.
DRAFT FOR CONSULTATION
Bibliographic
reference
Howard et al,
240
2004
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Breast & Oncology
(73 pts)
Interventio Ear nose throat (13
pts)
n1: n =
Gastrointestinal (122
127
Interventio pts)
Neurosurgery (34
n2: n =
pts)
121
Interventio Orthopaedic (62 pts)
Urology (58 pts)
n3: n =
Vascular Venous
128
Surgery (14 pts)
Stratificatio
All population:
n of pts:
Mean age: 58 (16 to
High risk:
88) yrs
291
M/F:158/218
Moderate
risk: 59
Low risk:
26
Total: 376
Intervention
Comparison
1. Kendall TED Thighlength
2. Medi thrombexin
Thigh-length
3. Medi
thrombexin kneelength
Additional
prophylaxis:
Subcutaneous
injection of 20 mg
LMWH the evening
before the surgery.
Enoxaparin injections
given daily until
discharge from
hospital
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Additional
prophylaxis:
Subcutaneous
injection of 20 mg
LMWH the
evening before the
surgery.
Enoxaparin
injections given
daily until
discharge from
hospital
283 of 648
Length of
follow up
Second
duplex
imaging
between
days 5-7
Outcome
measures
DVT Confirmed
by: Duplex
imaging
Effect size
Int1: 6/102
Int2: 2/93
Int3: 11/99
Comments
Not reported:
Proximal DVT,
Fatal PE, PTS,
Bleeding related
complications, QoL
and LoS
Pairwise
comparison:
Int1 vs Int3: OR 0.5
[0.18, 1.41], p = 0.19 Funding: Not
Int2 vs Int3: OR
reported
0.18 [0.04,0.82], p =
0.026
Preoperative
LMWH:
Int1 vs Int3: OR 0.5
[0.18,1.42], p =
0.132
Int2 vs
Int3: OR 0.19
[0.04,0.88], p =
0.034
Absolute: OR 0.41
[0.16,1.06], p =
0.066
DRAFT FOR CONSULTATION
Evidence Table 20: IPC – thigh-length versus calf-length
Bibliographic
reference
Soderdahl et
475
al, 1997
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 90
Interventio
n: n = 47
Control: n
= 43
Patients
characteristics
Intervention
Type: Thigh-length
Type of surgery:
Urological, Duration IPCD
of surgery not
reported
Comparison
Type: Calf-length
IPCD
Length of
follow up
Both
groups:
mean FU
10 months
(range 3-40
months). All
Intervention: Mean Timing: Begun preTiming: Begun
clinically
age: 64.8 (range 46- anaesthetic and
pre-anaesthetic
evaluated
90) M/F:67/67
continued until patient and continued
at 3 and 6
fully
ambulatory
or
until
until
patient
fully
Control: Mean age:
mo
discharge
ambulatory
or
until
58.6 (range 24-77)
discharge
M/F:92/77
Pre-existing risk
factors: previous
VTE, obesity,
malignancy,
congestive heart
failure, IBS, MI.
Additional noncomparative
prophylaxis: None
reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Additional noncomparative
prophylaxis:
None reported
284 of 648
Outcome
measures
DVT Confirmed
by: Bilateral
duplex US on
post-op day 3/4
and 6/7
Effect size
Int: 0/47
Control: 1/43
p value: 0.29
PE Confirmed by Int: 1/47
pulmonary
Cont: 0/43
angiography
p value: 0.33
Fatal PE (not
stated how
confirmed)
Int: 0/47
Cont: 1/43 (at 17
months
postoperatively
p value: 0.4778
Comments
Comments: Postsurgery. Interviews
with nursing
personnel
suggested that calflength IPCs were
easier to apply and
greater patient
satisfaction. Cost
analysis
Not reported: PVT,
PTS, Bleeding,
QoL, LoS, Survival,
funding.
DRAFT FOR CONSULTATION
Evidence Table 21: Mechanical vs mechanical
Bibliographic
reference
Anglen et al,
19
1998
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 117
Type of surgery:
Trauma patients with
Interventio fracture of pevic
ring, acetabulum or
n: n = 68
Control: n femur.
= 49
Intervention:
Average age: 38
(range: 17-82 yrs)
M/F: 38/30
Intervention
Intermittent plantar
compression devices
(foot pumps) NuTech
PlexiPulse).
Comparison
Sequential
gradient kneelength pneumatic
compression
devices (Kendall
Company)
Additional noncomparative
prophylaxis:
Not reported
Control: average
age: 41 (range: 1888 yrs) M/F: 27/22
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
285 of 648
Length of
follow up
Outcome
measures
Int: Day 2,
day 7 and
day 14 after
surgery if pt
still in
hospital
Cont: Day
2, day 7
and day 14
after
surgery if pt
still in
hospital
DVT Confirmed
by: Color duplex
US. On day 2, day
7 and day 14 after
surgery if pt still in
hospital
Int: 3/68
Control: 0/49
p value: not
reported
PE
Confirmed
by: Unknown
method 6 weeks
after surgery
Int: 1/68
Control: 0/49
p value: not
reported
Effect size
Comments
DRAFT FOR CONSULTATION
Mechanical vs mechanical
Bibliographic
reference
Hansberry et
208
al, 1991
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: n =
74
Intervention
1: n = 24
Intervention
2:n = 25
Control: n =
25
Type of surgery:
Patients undergoing
total urological
operation
Intervention
Comparison
Heparin
Intervention 1:
dihydroergotamine
External sequential
pneumatic
compression stockings Additional noncomparative
prophylaxis:
Interventions &
Intervention 2:
Not reported
control: Age range: Thromboembolic
45 - 75years
stockings
Pre-existing risk
factors: Malignancy,
Anaethesia
>90mins, one
person in Int 2 had a
history of a previous
DVT
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
286 of 648
Length of
follow up
Outcome
measures
6 days
postoperati
vely or
discharge if
sooner.
DVT (overall)
Confirmed
by:venography
and In-labelled
platelet scans
Int1: 3/24
Int2: 5/25
Control: 2/25
p value: not
reported
PE Confirmed
by:ventillation
perfusion scans,
platelet
scintigraphy and
lung scan - all
patients here had
DVT
Int 1: 1/24
Int 2: 1/25
Control: 1/25
p value: not
reported
Wound related
complications
Int 1: 1/24
Int 2: 2/25
Control: 1/25
p value: not
reported
Effect size
Comments
The paper did not
report any dropouts
Not reported:PTS,
Fatal PE, QoL,
Survival
DRAFT FOR CONSULTATION
Mechanical vs mechanical
Bibliographic
reference
Nicolaides et
385
al 1983
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total:
Intervention
1: n = 50
Intervention
2: n = 50
Control: n =
50
Patients
characteristics
Type of surgery:
Major abdominal
(& Duration of
surgery)
Intervention
Intervention1
Type: thigh-length
IPC + stockings
Timing: IPC device
worn during surgery
and for 72 hours postIntervention1:
op or until ambulant,
Mean age:
57.3±13.4 yrs M/F: then stockings until
discharge
Not reported
Intervention 2
Intervention2:
Type: UFH
Mean age:
58.6±13.3 yrs M/F: Dose: 5000 IU
Not reported
Timing: Begun 2 hrs
Control: Mean age: pre-op and repeated
twice daily until
59.2±16.6 yrs
discharge
M/F: Not reported
Comparison
Type: Electrical
calf stimulation
Dose: 12
impulses/min
Outcome
measures
All groups: DVT Confirmed
125
until
by: I FUT on
discharge alternate days
until discharge
Timing: Begun
after induction of
anaesthesia and
worn for duration
of operation
Additional noncomparative
prophylaxis:
Not reported
287 of 648
Effect size
Comments
No of patients:
Int1: 3/50 Int2:
7/50 Control:
12/50
p value: Not
reported
Comments:
Patients stratified
according to risk
(four levels) before
randomisation to
study groups.
No of limbs:
Int 1: 4/100
Int2: 9/100
Control: 18/100
Not reported: PE,
PTS, bleeding,
QoL, survival, LoS
p value:
Int 1 vs int 2: Not
significant
Int 1 vs cont <
0.0025
Int 2 vs control
<0.05
Proximal DVT
Confirmed by:
Pre-existing risk
factors: varicose
veins, previous DVT,
malignancy
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
Int1: 0/50 Int2: 1/50
Control: 2/50
p value: NR
Funding: Leventis
foundation. Berk
pharmaceuticals
(UK) provided UFH.
Kendall Coporation
provided IPC and
stockings
DRAFT FOR CONSULTATION
Mechanical vs mechanical
Bibliographic
reference
Ryan et al,
437
2002
Study
Type
RCT
Evidenc
e level
++
No. of
patients
Patients
characteristics
Intervention
Patients who were to Vena Flow pneumatic
undergo total hip
compression device
applied to both lower
Interventio arthroplasty.
extremities
n: n = 50
Control: n Intervention:
n = 50
Duration:
= 50
Mean age:70.1
Started immediately
Gender ratio
after surgery and
(M:F):19:31
continued for duration
(38%:62%)
of postoperative
hospital stay
Control:
n = 50
Mean age:67.5
Additional
Gender ratio
background
(M:F):19:31
prophylaxis
(38%:62%)
Aspirin (325mg 2x/day)
Total: 100
Epidural anaesthesia
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Elastic stockings
Length of
follow up
Until
discharge
(4-5 days
on
average)
Outcome
measures
Proximal DVT
(confirmed by
magnetic
resonance
venography)
Effect size
Int: 4/50 (8%)
Control: 11/50
(22%)
p value: < 0.05
Comments
Detailed findings of
the magnetic
resonance
venogram reported
eg: size and
location of clot etc.
No clinically
symptomatic DVT
or PE developed in
any patient.
Additional
background
prophylaxis
Aspirin (325mg
2x/day)
Epidural
anaesthesia
288 of 648
Symptomatic PE
Int: 0/50 (8%)
Control: 0/50
p value: N/A
Not reported:
DVT, PTS, QoL.
DRAFT FOR CONSULTATION
Mechanical vs mechanical
Bibliographic
reference
Silbersack et
469
al, 2004
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 131
Type of surgery:
Patients > 18 years,
Interventio awaiting primary
unilateral THR or
n: n = 68
TKR
Control: n
Intervention: No of
= 63
patients with THR:
33
No of pts with TKR:
35
MeanAge:63 (29 to
90)
Gender ratio
(M:F):28:40
Control:
No
of pts with THR: 28
No of pts with TKR:
35
MeanAge:65 (36 to
87)
Gender ratio
(M:F):19:44
Risk factors:
Intervention:
Previous VTE: 5/68
Varicose veins:
45/68
Previous cancer:
4/68
Oestrogen users:
4/68
Intervention
LMW Heparins plus
calf intermittent
pneumatic
compression devices.
Patients were given
40mg of anti-Xa
enoxaparin-natrium
daily beginning on the
eve prior to surgery
until postoperative day
30 (self
administration).
Additional noncomparative
prophylaxis:
Regional anaesthesia:
49/68
Comparison
LMW Heparins
plus GCS
Patients were also
given 40mg of
anti-Xa
enoxaparinnatrium daily
beginning on the
eve prior to
surgery.
Additional noncomparative
prophylaxis:
Regional
anaesthesia:
46/63
Aspirin users: 8/63
Non-steriodal antiinflammatory
drugs: 26/63
Aspirin users: 11/68
Non-steriodal antiinflammatory drugs:
25/68
Control:
Previous VTE: 3/63
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
289 of 648
Length of
follow up
Outcome
measures
First follow- DVT
up:
(confirmed by
between 6th colour duplex US)
th
and 12
postoperative
day
Second
follow-up:
between
6th and
12th postoperative
weeks.
Effect size
First follow up:
Int: 0/68
Control: 18/63
(28.6%) (P<0.0001)
Second follow up:
Only of 105 of 113
pts (93%) who
received prolonged
prophylaxis with
LMWH and GCS
One fresh
thrombosis case
detected.
PE
No cases of
(confirmed by
symptomatic PE.
spiral CT of lungs)
Comments
Unrestricted grant
from Aircast Europa
GmbH, Neubeuren,
Germany which
made the
VenaFlow system
during the study
period.
- IPC was often
used incorrectly t
the beginning of the
study.
- 27% of pts
stopped using IPC
prematurely.
- Night-time use of
IPC was refused.
- In comparison
with GCS, the IPC
requires more
supervision.
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Varicose veins:
39/63
Previous cancer:
2/63
Oestrogen users:
2/63
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
290 of 648
Length of
follow up
Outcome
measures
Effect size
Comments
DRAFT FOR CONSULTATION
Mechanical vs mechanical
Bibliographic
reference
Study
Type
Stannard et al, RCT
483
2001
Evidenc
e level
.
No. of
patients
Total: 140
Interventio
n: n = 54
Control: n
= 53
Patients
characteristics
Intervention
Type of surgery:
Orthopaedic (hip
fracture) Duration
not stated
Type: bilateral thighcalf low pressure
compression device
Dose: 45mm Hg
Age and gender not
reported
Timing: (duration)
mean 20.8 hrs/day
(range 4 - 24hrs/day)
(time started) as soon
as possible following
admission to trauma
service (time finished)
discharge
Pre-existing risk
factors: All patients
had sustained a
pelvic or acetabular
fracture due to blunt
trauma requiring
surgery. Injury
severity scores
recorded
Comparison
Type: bilateral
combination calffoot high pressure
compression
device Dose: 160
mm Hg
Length of
follow up
FU to
discharge
Control:
mean 6.0
days postsurgery
Timing: (duration) Int: mean
mean 21.3 hrs/day 6.5 days
post(range 7 surgery
24hrs/day) (time
started) as soon
as possible
following
admission to
trauma service
(time finished)
discharge
Additional noncomparative
prophylaxis:
Not reported
Outcome
measures
Effect size
DVT Confirmed
by: Duplex US,
MRI
Int: 10/54
Control: 5/53
p value: 0.265 Not
significant
Fatal PE
Confirmed by:
Int:
Control:
p value:
(Significant/Not
significant)
Survival
134/140. Deaths not
due to PE, don't
know which groups
these patients
belonged too
Comments
33 patients dropped
out. Paper doesn't
state how many
were lost from each
group. Check
comparison. May
be best considered
to be IPC (leg) vs
IPC +footpump (if
length of IPC
doesn't make a
significant
difference). Also
reported whether
DVTs were
occlusive or nonocclusive and > or
< 2 cm in size.
Increased patient
age and time
elapsed from injury
to surgery were
associated with
higher rates of
thrombosis
Not reported:
PE, QoL, LoS,
PTS, Bleeding
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
291 of 648
DRAFT FOR CONSULTATION
Mechanical vs mechanical
Bibliographic
reference
Wood et al,
557
1997
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 160
Patients
characteristics
Type of surgery:
Anterior lumbar
interbody fusion,
posterior spine
fusion, posterior
lumbar interbody
fusion, thigh-high
graduated
compression
stockings
134
completed
the study.
Not stated
to which
arms the
dropouts
were
randomised
Excluded:
.
History of VTE,
Interventio preoperative
assessment of at
n: n = 75
Control: n risk of DVT,
congestive heart
= 59
failure, previous
anticoagulation
treatment,
contraindications to
compression device
use such as
neuropathy, infection
or chronic venous
stasis.
Intervention
Comparison
Thigh high
sequential
Pneumatic
Started at surgery and Compression
worn until ambulatory, Wrap (Kendall) on
then worn when in bed both legs
until discharge
Started at surgery
and worn until
ambulatory, then
worn when in bed
Additional nonuntil discharge
comparative
prophylaxis:
Additional nonThigh-high
compression stockings comparative
started before surgery prophylaxis:
Thigh-high
and worn for hospital
compression
course.
stockings started
before surgery
and worn for
hospital course.
Foot wraps (Plexi
Pulse) to both feet
Intervention: Mean
age: 39.4 (sd 17.2)
yrs M/F: 39/36
Control: Mean age:
39.6 (sd 18.5) yrs
M/F: 39/20
Weight (mean):
Int: 80.3kg
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
292 of 648
Length of
follow up
Scanning
carried out
between
postoperative
days 5 and
7
Outcome
measures
Effect size
DVT Confirmed
by: Duplex US
Int: 1/75
Control: 0/59
p value: 1.0000
PE
Confirmed
by: Duplex US
Int: 1/75
Control: 0/59
p value: 1.0000
Visual analogue
comfort scale
(mean +SD)
Int: 5.84 +2.8
Cont: 5.56 +2.9
p value: 0.88
Comments
Comments: 36
patients (26%)
complained of
redness, itching, or
actual discomfort
with the use of the
devices. No
symptomatic DVTs
of PEs
Not reported:
Survival, PTS,
bleeding related
complications, QoL
and LoS
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Control: 68.5kg
p value: 0.001
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
293 of 648
Length of
follow up
Outcome
measures
Effect size
Comments
DRAFT FOR CONSULTATION
Evidence Table 22: Electrical stimulation vs no prophylaxis
Bibliographic
reference
Browse et al
80
1970
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 110
(220 legs)
Intervention
: n = 110
Control: n =
100
Type of surgery:
Mixed general
(abdominal, hernia,
head and neck,
mastectomy)
(&
Duration of surgery)
Exclusions:
Leg operations,
aorta-iliac arterial
surgery or any
operation in which
the iliac veins or
vena cava were
exposed and likely
to be damaged.
Intervention
Type: Electrical calf
stimulation Dose: 1
pulse/2 sec
Timing: Begun after
induction of
anaesthesia and worn
for duration of
operation
Comparison
Nil prophylaxis
Additional noncomparative
prophylaxis: All
patients were
encouraged to
exercise and had
chest
physiotherapy
Additional noncomparative
prophylaxis: All
patients were
encouraged to
exercise and had chest
physiotherapy
Mean age: 60 yrs
(range 40-81)
M/F:57/53
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
294 of 648
Length of
follow up
Three
weeks
postoperatively
Outcome
measures
DVT Confirmed
125
by: I FUT on
th
1,3,5 post-op
days
Proximal DVT
Assessme Confirmed by:
nt for DVT
carried out
on the 5th
postoperative
day
Effect size
Int: 9/110
Control: 23/110
p value: <0.001
Int: 0/110
Control: 0/110
p value: N/A
Comments
Patient’s other leg
acted as control.
Stimulated leg
determined
randomly
Not reported: PE,
PTS, Bleeding,
QoL, survival, LoS
DRAFT FOR CONSULTATION
Electrical stimulation vs no prophylaxis
Bibliographic
reference
Study
Type
Lindstrom et al RCT
329
1982
Evidenc
e level
1+
No. of
patients
Total: 112
Patients
characteristics
Intervention
Intervention 1:
Type: Electrical calf
stimulation. 50msec
Interventio
impulses. Groups of
n
Mean (range)
1: n = 37
duration of surgery impulses giving short
lasting tetanus of calf
Interventio in hours:
muscles
n
Int 1: 1.9 (0.5-6.5)
2: n = 35
Int 2: 2.4 (0.5-11)
Control: n Cont: 2.0 (0.5-5.75) Timing: During entire
operation only
= 40
Mean (range) age
in years:
Int 1: 63.7 (30-83)
Int 2: 66.7 (44-86)
Cont: 66.5 (45-86)
Type of surgery:
Major abdominal
Pre-existing risk
factors:
All patients aged >
40
Malignant disease
Int 1: 13/37
Int 2: 11/35
Cont: 13/40
Previous history of
VTE
Int 1: 0/37
Int 2: 3/35
Cont: 1/40
Comparison
Nil prophylaxis
10 days
Outcome
measures
Timing: 500 ml
perioperatively and on
1st and 3rd post-op day
295 of 648
Effect size
DVT Confirmed
by FUT
Int 1: 5/37
Int 2: 7/35
Control: 12/40
p values
Int 1 to control:
0.081
Int 2 to control:
0.32
Int 1 to Int 2: 0.46
DVT in patients
with malignant
disease
Confirmed by FUT
Int 1: 2/13
Int 2: 4/11
Control: 7/13
p values:
Int 1 to control:
0.039
Int 2 to control:
0.39
Int 1 to Int 2: 0.23
PE Confirmed by
scintigraphy and
chest x-ray
together
Int 1: 6/37
Int 2: 4/35
Control: 14/40
p value:
Int 1 to control:
0.06
Int 2 to control:
0.017
Int 1 to Int 2: 0.56
PE in patients
with malignant
disease
Confirmed by
scintigraphy and
chest x-ray
together
Int 1: 4/13
Int 2: 1/11
Control: 4/13
p value:
Int 1 to cont: not
significant
Int 2 to control:
0.19
Int 1 to Int 2: 0.19
Additional noncomparative
prophylaxis:
Not reported
Intervention 2:
Type: Dextran 40
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
Comments
Not reported:
fatal PE, PTS, QoL,
survival, LoS and
funding
DRAFT FOR CONSULTATION
Evidence Table 23: Patient views on mechanical prophylaxis
Bibliographic
reference
Barker and
Hollingsworth,
31
2004
Study
Type
Survey
Evidenc
e level
3
No. of
patients
Total: 218
Patients
characteristics
Type of surgery:
Miixed surgical
patients from 16
wards in one
hospital
Intervention
Comparison
Not applicable
Type: Graduated
compression stockings
Additional non(GCS)
comparative
prophylaxis:
Survey of concordance Not reported
with hospital policy of
wearing thigh-length
stockings after
surgery.
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
296 of 648
Length of
follow up
1 day
Outcome
measures
No of patients
wearing GCS in
accordance with
hospital policy
Effect size
9/218 (4%)
No of patients
99/218 (46%)
wearing any GCS
No of patients
wearing thigh
GCS
14/99 (14%)
No of patients
wearing thigh
GCS correctly
9/14 (64%)
No of patients
wearing below
knee GCS
85/99 (86%)
No of patients
wearing below
knee GCS
correctly
77/85 (91%)
Comments
The 5/14 wearing
thigh high GCS
incorrectly had
them rolled down to
below the knee.
This leads to
graduated
compression loss
and a constriction
band formed by the
rolled down band.
Staff not routinely
offering thigh high
stockings.
DRAFT FOR CONSULTATION
Patient views on mechanical prophylaxis
Bibliographic
reference
Benko et al,
41
2001
Study
Type
Evidenc
e level
3
Patient
views of
interventi
ons from
RCT
No. of
patients
Patients
characteristics
Intervention
Type of surgery:
Type: Thigh-length
Orthopaedic patients graduated
compression stockings
5
(GCS)
randomised
groups:
n = 80
2 brands of
thigh-length
2 brands of thighstockings
length, 40 in each
with 40
group
patients in
each arm
Additional non2 brands of
comparative
knee-length
prophylaxis:
stockings
Not reported
with 40
patients in
each arm
1 group of
no
intervention
.
Total: 200
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Type:
Below knee
graduated
compression
stockings
n = 80
2 brands of thighlength, 40 in each
group
Additional noncomparative
prophylaxis:
Not reported
297 of 648
Length of
follow up
1 hour
Outcome
measures
Effect size
No. patients with
wrinkles in
stockings after 1
hour
Int: 14/80
Cont: 6/80
p value: <0.05
No. patients
reporting
discomfort after
1 hour
Int: 17/80
Cont: 9/80
p value: <0.05
No. patients
unable to
manage
stockings
independently
Int: 38/80
Cont: 40/80
p value: >0.1
Comments
Main aim was to
investigate the
difference in
venous
haemodynamics in
inpatients prior to
surgery. Only
results for patient
views reported
here.
DRAFT FOR CONSULTATION
Patient views on mechanical prophylaxis
Bibliographic
reference
Robertson et
429
al, 2000
Study
Type
Evidenc
e level
Compara 2
tive study
No. of
patients
Total: 224
Interventio
n: n = 120
Control:
n = 104
Patients
characteristics
Type of surgery:
Hip replacement
Intervention
Type: Foot pumps
(Plexiplus)
Duration: started on
day of surgery and
continued until
postoperative day 3
Comparison
Type: Thigh high
sequential
compression
devices (SCD)
(Kendall) +
graduated
compression
stockings
Warfarin or heparin
was also given to
some patients at the
discretion of the
surgeon
Duration: 4
postoperative
days
Additional noncomparative
prophylaxis:
Not reported
Warfarin or
heparin was also
given to some
patients at the
discretion of the
surgeon
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
298 of 648
Length of
follow up
4 days
Outcome
measures
Average no. of
hours per day
devices worn
Effect size
Int: 64.10 hours
Control: 60.85
hours
p value: 0.078
No. of patients
Int: 85/120
responding as
Control: 57/104
'comfortable' or no p value: 0.037
complaints with
intervention
Reasons for noncompliance with
foot pumps
Painful to foot/heal:
5/120
Forceful pulsation:
4/120
Tight: 3/120
Blisters: 1/120
Reasons for noncompliance with
sequesntion
compression
Hot/sweaty: 14/104
Stockings
bothersome: 9/104
Tight: 4/104
Itchy: 4/104
Blisters: 2/104
Preference for
device in foot
pump patients
having revision
surgery who had
previously
received SCD.
Foot pump:
24/35 (68.6%)
SCD:
7/35 (20%)
p value: <0.005
No preference:
4/35 (11.4%)
Comments
DRAFT FOR CONSULTATION
Patient views on mechanical prophylaxis
Bibliographic
reference
Westrich et
544
al, 2003
Study
Type
Evidenc
e level
Prospecti 3
ve case
series
No. of
patients
Total: 100
Patients
characteristics
Type of surgery:
Knee arthroplasty
Intervention
Type:
Pulsatile pneumatic
plantar compression
PlexiPluse foot wrap
Comparison
not applicable
Observation started
postoperatively and
continued until device
no longer used.
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
299 of 648
Length of
follow up
1 hour
Outcome
measures
Effect size
Comments
Total
'compliance'
recorded by
observer (total
time of observed
use / total time
observed)
Nurses:
5537/6356 hours
(87.1%)
Researchers:
1314/1970 hours
(66.7%)
Combined nurses
and researchers:
6851/8426 hours
(81.3%)
For time used there
are two lots of
results assessed:
nurses assessed
use for 24 hours
per day, research
team assessed use
between 9am and
5pm.
Actual
'compliance'
recorded by
observer (total
time of observed
use / total time
observed that a
patient can use
the device)*
Nurses:
5537/5957 hours
(92.9%)
Researchers:
1314/1646 hours
(79.8%)
Combined nurses
and researchers:
6851/7603 hours
(90.1%)
*Actual compliance
excluded times
when the device
had to be removed
such as going to
physiotherapy,
ambulatory
activities, hygiene
and for tests
conducted in
another room.
DRAFT FOR CONSULTATION
Patient views on mechanical prophylaxis
Bibliographic
reference
Wood et al,
557
1997
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 134
Type of surgery:
Anterior lumbar
Interventio interbody fusion,
posterior spine
n: n = 75
Control: n fusion, posterior
lumbar interbody
= 59
fusion,
Intervention
Comparison
Patients wore
Patients wore thighthigh-high
high compression
stockings + Foot wraps compression
stockings +
Sequential
Additional nonPneumatic
comparative
Compression
prophylaxis:
Wrap
Not reported
Intervention: Mean
age: 39.4 (sd 17.2)
yrs M/F: 39/36
Control: Mean age:
39.6 (sd 18.5) yrs
M/F: 39/20
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
300 of 648
Length of
follow up
Scanning
carried out
between
postoperative
days 5 and
7
Outcome
measures
Effect size
DVT Confirmed
by: Duplex US
Int: 1 Control: 0
p value: N/A
PE
Confirmed
by: Duplex US
Int: 1 Control: 0
p value: N/A
Visual analogue
comfort scale
(mean +SD)
Int: 5.84 +2.8
Cont: 5.56 +2.9
p value: 0.88
Comments
Comments: 36
patients (26%)
complained of
redness, itching, or
actual discomfort
with the use of the
devices. No
symptomatic DVTs
of PEs
Not reported:
Survival, PTS,
bleeding related
complications, QoL
and LoS
DRAFT FOR CONSULTATION
Evidence Table 24: Oral anticoagulants vs no prophylaxis
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Roderick et al, Systemat 1+
430
2005
ic review
Total:
884
9 RCTs
included
Int: 524
Cont: 491
68,159,204,337,374,40
Patients
characteristics
Type of surgery:
orthopaedic: 6
studies
gynaecological: 3
studies
6,412,415,495
Pre-existing risk
factors:
not reported
Intervention
Oral anticoagulant
Dose:
Adjusted dose: 6
studies
Fixed dose: 2 studies
Adusted/fixed: 1 study
Timing:
Start time varied from
admission or 1 week
preoperatively to
postoperatively.
Comparison
Outcome
measures
Effect size
No prophylaxis: 5 End time
DVT Confirmed by Int: 91/455
varied from venography or
studies
Control: 164/429
Placebo: 4 studies 1 week to 3 FUT
p value: 0.0000
months
Additional noncomparative
prophylaxis:
none
Additional noncomparative
prophylaxis:
none
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
301 of 648
PE (scan, x-ray or
post-mortem for
fatal)
Int: 0/163
Cont: 12/162
p value: 0.0002
Major bleeding:
definition not
given
Int: 45/449
Cont: 23/417
p value: 0.0160
Proximal DVT
Int: 12/254
Cont: 29/257
p value: 0.0085
Comments
Not reported:
LoS, QoL, PTS
DRAFT FOR CONSULTATION
Oral anticoagulants vs no prophylaxis
Bibliographic
reference
Mismetti et al,
365
2004
2 RCTs
146,378
included
Study
Type
Evidenc
e level
Systemat 1+
ic review
No. of
patients
Total:
305
Patients
characteristics
Type of surgery:
Orthopaedic: 2
studies
Intervention
Comparison
Type: Oral
anticoagulant
(adjusted)
Phenindione (1 study)
Warfarin (1 study)
No prophylaxis: 1
study
Placebo: 1 study
Timing:
Postoperative: 2
studies
Administered until
discharge (1 study)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Additional noncomparative
prophylaxis:
none
302 of 648
Length of
follow up
3 months (I
study)
3 weeks (1
study)
Outcome
measures
Effect size
DVT Confirmed by Int: 9/44
venography or
Cont: 22/41
FUT
p value: 0.0018
Fatal PE
Defined as
specified in each
report.
Int: 1/144
Cont: 2/141
p value: 0.6197
PE
Int: 4/144
Cont: 16/141
p value: 0.0050
Major bleeding
Int: 1/100
Cont: 2/100
p value: 1.0000
Comments
Not reported:
LoS, QoL, PTS
Funding: SanofiSynthelabo grant
DRAFT FOR CONSULTATION
Evidence Table 25: Oral anticoagulants adjuvant
Bibliographic
reference
No. of
patients
Patients
characteristics
Roderick et al, Systemat 1+
430
2005
ic review
Total: 688
5 RCTs
included
2 studies
report total
in both
arms so
unable to
calculate
totals for
intervention
and control.
Orthopaedic (3
studies), Mixed (1
study) and
Neurosurgery (1
study)
252,298,432,516,558
Study
Type
Evidenc
e level
Intervention
OAC adjusted + GCS
(2 studies)
OAC-adjusted +
Dextran
OAC-adjusted + UFH
OAC-adjusted + IPC
Comparison
GCS (2 studies)
Dextran (1 study)
UFH (1 study)
IPC (1 study)
Timing: recovery room
Open studies: 4
(1 study), admission,
Placebo: 1
preop (2 studies) and
day one post op (1
study).
Additional noncomparative
Additional nonprophylaxis:
comparative
Not reported
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
303 of 648
Length of
follow up
Not
reported
Outcome
measures
Effect size
DVT confirmed by
FUT, venography,
duppler US
Int: 20/165
Cont: 34/184
p value: 0.1057
PE confirmed by
scan or post
mortem for fatal
Int: 2/182
Cont: 6/199
p value: 0.2878
Major bleeds:
Int: 4/126
Cont: 1/141
p value: 0.1917
Proximal DVT
Int: 7/108
Cont: 11/119
p value: 0.4724
Comments
Not reported: QoL,
LoS and PTS.
DRAFT FOR CONSULTATION
Evidence Table 26: Oral anticoagulants – adjusted vs fixed dose
Bibliographic
reference
Study
Type
Evidenc
e level
Roderick et al, Systemat 1+
430
2005
ic review
2 RCTs
154,412
included:
No. of
patients
Patients
characteristics
Total: 267
Int: 135
Cont: 132
Type of surgery:
Orthopaedic (1
study)
Gynaecological (1
study)
Intervention
OAC-adjusted
Comparison
OAC-fixed
Warfarin 1 mg
1st study:
warfarin adjusted
INR 2-4
Timing: Night preop to
day 3 postop (fixed)
than adjuvant
Timing:
1st study night
preop to 14 days
post op.
2nd study mean
20d preop to
discharge.
2nd study:
Nic adjusted
Additional nonINR 2.4
Timing: 5 day preop to comparative
prophylaxis:
discharge
Not reported
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
304 of 648
Length of
follow up
NR
Outcome
measures
Effect size
DVT confirmed by
venography or
fibrinogen
uptake/Doppler
US
Int: 17/133
Cont: 33/129
p value: 0.0114
PE (scan)
Int: 1/98
Cont: 0/97
(reported in 1 study)
p value: 1.0000
Major bleeds
Int: 8/135
Cont: 6/132
p value: 0.7850
Proximal DVT
Int: 4/98
Cont: 11/97
(reported in 1 study)
p value: 0.0650
Comments
Not reported: LoS,
QoL, PTS
DRAFT FOR CONSULTATION
Oral anticoagulants – adjusted vs fixed dose
Bibliographic
reference
Bern et al,
57
2002
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 98
(20
excluded)
Intervention
: n = 43
Control: n =
35
Patients
characteristics
Type of surgery:
Unilateral total hip
replacement (for
degenerative
disease).
Intervention: (49
patients
randomised) Mean
age: 61.9 Range:
31-91 yrs
M/F:25/24
Control: (49
patients
randomised)
Mean age: 65.3
Range: 29-84 yrs
M/F:30/19
Pre-existing risk
factors:
Intervention
Type: adjusted dose
warfarin
Dose: 5mg pre-op,
then PT 1.3 – 1.5 x
normal
Comparison
Type: fixed lowdose warfarin
Dose: 1 mg
Timing: begun 7
days pre-op and
Timing: 5 mg eve pre- continued until 6th
op, then adjusted dose week
until 6th week
Additional noncomparative
Additional nonprophylaxis:
comparative
stockings. 29/49
prophylaxis:
originally
stockings. 23/49
randomised
originally randomised
received dextrans
received dextrans
intraoperatively
intraoperatively
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
305 of 648
Length of
follow up
Both
groups: 6
weeks
post-op
Outcome
measures
Effect size
Int: 0/43
DVT Confirmed
Control: 0/35
by:
p value: 1.0000
Doppler duplex
US at discharge or
7 days post-op.
Repeated at 6
week FU
PE
Confirmed
by:
Not routinely
assessed. Clinical
suspicion
investigated with
V/Q and
angiogram
Int: 0/43
Control: 0/35
p value: 1.0000
Bleeding related
complications
Estimated
perioperative
blood loss (mL)
Transfusion
requirements
(units)
Perioperative
blood loss mean
(range)
Int: 625 (200 –
2,250)
Control:
557 (200 – 1400)
p value: Not
significant
Transfusions given
mean (range)
Int: 2.4 (0-5)
Control: 2.3 (0-5)
p value: Not
significant
Comments
Comments: 6
patients excluded
from adjusted dose
and 14 from fixed
dose group.
Difference in
withdrawals due to
8 patients. 1
withdrawal from
each group
developed DVT.
Not reported:
Proximal DVT,
PTS, QoL, Survival,
LoS
Funding: Study
supported by
donations to the
Foundation for
Hematology
Research, and
residual funds from
previous grant from
Dupont
Pharmaceuticals
Company
(Wilmington, DE)
DRAFT FOR CONSULTATION
Evidence Table 27: Oral anticoagulants timing
Bibliographic
reference
Francis et al,
163
1996
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total:
220
Patients
characteristics
Type of surgery:
Elective knee
replacement
Interventio
Intervention
n: 110
mean +SD age: 69
Control:
110
+10 years (n = 95)
110
randomised
into each
arm but 24
excluded
from
analysis of
DVT and
12
excluded
from
analysis of
bleeding*
Control
mean +SD age: 69
+ years (n = 101)
Pre-existing risk
factors:
History of venous
thromboembolism
Int: 15 (n = 95)
Cont: 21 (n = 101)
Intervention
Warfarin:
Preoperatively 2.5mg
alternating with 5mg
daily.
Dose: adjusted to
achieve and INR of
approximately 1.5 on
day of surgery. Postoperatively dose
adjusted to achieve a
target INR of 2.2
Timing:
Started 10-14 days
preoperatively and
continued until
venography between
postoperative day 5
and 9
Additional noncomparative
prophylaxis:
Thigh-high GCS on
both legs (all patients)
Continuous passive
motion in recovery
room (most patients)
Regional Anaesthesia:
75 (n = 95)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Warfarin: Initial
dose based on
weight,
subsequent daily
doses adjusted to
achieve a INR of
2.2
Timing:
Started the night
before surgery
and continued
until venography
between
postoperative day
5 and 9
Additional noncomparative
prophylaxis:
Thigh-high GCS
on both legs (all
patients)
Continuous
passive motion in
recovery room
(most patients)
Regional
Anaesthesia 82 (n
= 101)
306 of 648
Length of
follow up
Outcome
measures
Postoperati
vely
between
day 5 and 9
DVT Confirmed by
bilateral or
unilateral
venography
Int: 37/95
Cont: 38/101
p value: not
significant
Proximal DVT
Confirmed by
venography
Int: 5/95
Cont: 7/101
p value: not
significant
PE (symptomatic)
Int: 0/95
Cont: 0/101
not significant
Major bleeding
complications
Int: 5/103
Cont: 2/105
p value: (not
reported)
Total bleeding
complications
Int: 11/103
Cont: 9/105
p value: (not
reported)
Mean + SD units
of blood
transfused
Int: 1.33 +1.26 (n =
103)
Cont: 0.95 +1.22 (n
= 105)
p value: <0.05
Effect size
Comments
Comments:
Not reported:
PE, LoS, QoL,
PTS,
Also reported:
DVT confined to
calf veins,
thrombosis of the
minor veins, lowest
postoperative
haematocrit count
Exclusions
No surgery or
prophylaxis:
Intervention: 7
Control: 5
No venography
Intervention: 8
Control: 4
Funding:
National Heart,
Lung and Blood
Institute, National
Institutes of Health.
DRAFT FOR CONSULTATION
Oral anticoagulants timing
Bibliographic
reference
Swierstra et
492
al, 1988
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 101
Intervention
: n = 50
Control: n =
51
Patients
characteristics
Type of surgery:
Total hip
replacement
Intervention
Type: Acenocoumarol
starting 4 days pre-op
Dose: 3mg pre-op
then INR 2.1.
Mean duration of
surgery: (mins)
Intervention: 178 ±
34 Control: 175 ±
27
Timing: Begun 4 days
pre-op. 3mg daily on
4th and 3rd day pre-op,
then adjusted dose
aiming for INR of 1.5Intervention: Mean 1.6 during surgery.
age: 66±11 yrs
Post-op adjusted dose,
M/F:13/37
INR 2.1 until
discharge.
Control: Mean age:
66±10 yrs M/F:7/44 Additional noncomparative
Pre-existing risk
prophylaxis:
factors: previous
None reported
history of VTE,
varicosis.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Type:
Acenocoumarol
Dose: 3mg preop then INR 2.1.
Timing: 3mg 1
day pre-op and
day of op, then
adjusted dose INR
2.1 until
discharge.
Additional noncomparative
prophylaxis:
None reported
307 of 648
Length of
follow up
Outcome
measures
Both
groups: to
discharge
Proximal DVT
Confirmed by:
Venography
(99mTc plasmin),
10 days post-op
Int: 12/50
Control: 11/51
p value: Not
significant
Bleeding related
complications
Perioperative
blood loss –
amount of blood in
suction apparatus,
weight of gauzes
Post-operative
blood loss –
contents of drain
bottles
No of blood
transfusions
Perioperative
blood loss:
Int: 1.11± 0.52 L
Control: 1.2. ±
0.62 L
p value:
Not significant.
Effect size
Postoperative
blood loss:
Int: 0.6 ± 0.41 L
Control: 0.58 ±
0.33L
p value:
Not significant
Comments
Comments:
Unclear how many
patients were
randomised and
how many of these
were excluded. 17
intervention and 22
control patients
used NSAIDs.
Analysis showed no
relationship
between NSAID
use and
development of
Proximal DVT
Not reported: Calf
vein thrombi, PE,
PTS, QoL, LoS,
survival, funding
DRAFT FOR CONSULTATION
Evidence Table 28: Oral anticoagulants duration
Bibliographic
reference
Prandon et al,
416
2002
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Type of surgery:
Total hip
arthroplasty.
Intervention Duration of surgery
: n = 184 not reported
Control: n =
Intervention:
176
Median age: 68
range: 48 - 82 yrs
M/F:83/101
Total:
360
Control: Median
age: 69 range: 44 87 yrs M/F:79/97
Intervention
Comparison
Type: Extended
warfarin Dose:
5mg pre-op then
adjusted dose INR 2.0
– 3.0
Type: Warfarin
Dose: 5mg preop then adjusted
dose INR 2.0 –
3.0
Timing: 5mg 2nd day
pre-op then adjusted
dose INR 2.0 – 3.0
continued for 4 weeks
Timing: 5mg 2
day pre-op then
adjusted dose INR
2.0 – 3.0 until
discharge (mean 9
days)
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
nd
Additional noncomparative
prophylaxis:
Not reported
308 of 648
Length of
follow up
Outcome
measures
Both
groups: 4
weeks.
Patients
observed
for further 2
months.
Proximal DVT
Confirmed by:
Bilateral Doppler
US of proximal
venous system at
1, 2, and 4 weeks
post-op
Int: 1/184
Control: 8/176 (3
symptomatic)
p value: not
reported. RR of
developing VTE
statistically
significant
PE
Not
routinely
assessed.
Symptomatic PE
confirmed by V/Q,
spiral CT or
angiography
Int: 0/184
Control: 1/176
p value: not
reported. RR of
developing VTE
statistically
significant
Fatal PE
Confirmed by:
autopsy or where
PE could not be
ruled out
Int: 0/184
Control: 0/176
p value: Not
reported
Major bleeding.
Defined as 1.
clinically overt and
associated with
either a decrease
in haemoglobin of
at least 2.0 g/dL or
requiring
transfusion of 2 or
more units of red
blood cells 2.
intracranial or
retroperitoneal 3.
resulted in
permanent
Int: 1/184
Control: 0/176
RR and statistical
significance: Not
reported
Effect size
Comments
Comments: Study
prematurely
terminated after
360 patients
because of
statistically
significant and
clinically relevant
superiority of
extended over
short-term
prophylaxis
observed. 3
patients from each
group violated
protocol, but ITT
analysis performed.
In the following 2
months 2
symptomatic VTE
events occurred in
intervention group.
Not reported:
Distal DVT, PTS,
QoS, LoS, funding
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Length of
follow up
Outcome
measures
discontinuation of
anticoagulation
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
309 of 648
Effect size
Comments
DRAFT FOR CONSULTATION
Evidence Table 29: Oral anticoagulants vs unfractionated heparin
Bibliographic
reference
Study
Type
Evidenc
e level
Roderick et al, Systemat 1+
430
2005
ic review
4 RCTs
included:
252,413,495,516
No. of
patients
Total: 553
Int: 112
Cont: 110
Note:
One study
reported
331
subjects
but not
broken
down
between
the two
arms.
Patients
characteristics
Type of surgery:
Orthopaedic: 2
studies
Gynacological: 1
study
Mixed surgery: 1
study
Intervention
Comparison
OAC-adjusted
UFH
Dose:
Warfarin adjusted
Warfarin 1 mg
Nicoumalone adjusted
Acenocoumarin
adjusted
Dose:
H50000IU (three
studies) and H45000 placebo
OAC (one study).
All taken
subcutaneously.
Background agent:
Timing:
GCS inone study
and Placebo dextran 7 days preop to 1 day
postoperatively.
in one study.
Dose ended between
7-14 days
postoperatively.
Additional noncomparative
prophylaxis:
Not reported
Timing:
2 hours
preoperativelyin
all the studies.
Continued until
postop (1 study),
days 9-14 (one
study), day 7 (in
one study) and not
reported in final
study.
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
310 of 648
Length of
follow up
Outcome
measures
Effect size
From day 1 DVT: confirmed
Int: 41/176
to day 14.
Cont: 29/184
by fibrinogen
uptake, venograph p value: 0.0834
or doppler US
PE by scan,
angiogram, X-ray
or post-mortem
Int: 9/80
Cont: 5/80
(reported from one
study
p value: 0.4022
Major Bleeds:
Int: 8/192
Cont: 15/190
p value: 0.1376
Proximal DVT
Int: 3/31
Cont: 0/37
(reported from one
study)
p value: 0.0897
Comments
Not reported: LoS,
QoL, PTS.
DRAFT FOR CONSULTATION
Oral anticoagulants vs UFH
Bibliographic
reference
Mismetti et al,
365
2004
2 RCTs
29,443
included
Study
Type
Evidenc
e level
Systemat 1+
ic review
No. of
patients
Patients
characteristics
Total: 1366 Type of surgery:
Orthopaedic (2
(2 studies) studies)
Intervention
Comparison
Type: Warfarin (1
study)
Acenocoumarol (1
study(
Type: UFH
5000x2 for 3
weeks (1 study)
Timing: postoperative
both studies
Preoperative (2
studies)
3 weeks (1 study)
6 weeks (1 study)
11-14 days
Outcome
measures
DVT (Clinical,
confirmed by US
or veno/FUT)
Effect size
Int: 54/694
Cont: 52/662
p value: 1.0000
Comments
Not reported:
LoS, QoL, PTS
6 weeks
LMWH (Reviparin
4200 IU x1) for 6
weeks
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
311 of 648
Major Bleeding
Int: 35/645
Cont: 9/644
p value: 0.0001
Proximal DVT
Int: 4/636
Cont: 3/636
p value: 1.0000
Funding: SanofiSynthelabo grant
DRAFT FOR CONSULTATION
Oral anticoagulants vs UFH
Bibliographic
reference
Study
Type
RCT
Van
Vroonhoven et
518
al, 1974
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Intervention
Total: 100
Intervention
: n = 50
Control: n =
50
Type of surgery:
General
(&
Duration of surgery)
Type: acenocoumarol
Dose: PTT 5-10% of
normal
Intervention: Mean Timing: Begun on
evening of day of op,
age59 yrs
or 1st post-op day.
M/F:NR
Continued for 7 days
Control: Mean age:
52 yrs M/F: NR
Additional noncomparative
Pre-existing risk
prophylaxis: Routine
factors: Obesity,
post-op physiotherapy
Malignancy,
Diabetes, Varicose
veins (no significant
differences between
groups)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Type: LDUH
Dose: Not given
Timing: Begun 2
hrs pre-op and
repeatedly 12
hourly for 8 days
Additional noncomparative
prophylaxis:
Routine post-op
physiotherapy
312 of 648
Length of
follow up
Both
groups: 7
days
Outcome
measures
Effect size
DVT Confirmed
by: Bilateral
radioiodine (I,
125) fibrogin
uptake test on
days 0, 1, 3, 5, 7
post-op.
Int: 9/50
Control: 1/50
p value: <0.025
(Significant)
Bleeding related
complications
Peri-operative
blood loss
Int: mean 436 ml
(s.d. 584)
Control: mean 317
ml (s.d. 303)
p value: reported
as not significant
Comments
Comments:
Thrombosis in OAC
patients was
associated with
longer operation (p
= 0.01) and greater
peri-operative blood
loss (p = 0.007). 1
OAC patient
developed clinical
symptoms of PE.
Not reported:
Proximal DVT, PE,
PTS, QoL, survival,
LoS, funding
DRAFT FOR CONSULTATION
Evidence Table 30: Oral anticoagulants vs low molecular weight heparin
Bibliographic
reference
Study
Type
Evidenc
e level
Roderick et al, Systemat 1+
430
2005
ic review
9 RCT studies
included
156,164,171,186,206,2
26,244,247,320
No. of
patients
Patients
characteristics
Total: 7260 Type of surgery:
Orthopaedic: 9
Int: 3197
Cont: 4063
Intervention
OAC-adjusted
Warfarin adjusted ( 5
studies), warafarin
fixed (3 studies) and
Acenocourmarin
adjusted International
Normalised Ratio 2-3
(1 study)
Comparison
LMWH
Timing:
Ranged from time
admitted to 14
days
postoperatively/dis
charge
Timing:
Ranged from time
Additional nonadmitted to 14 days
postoperatively/dischar comparative
prophylaxis:
ge
Not reported
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
313 of 648
Length of
follow up
Between
day 1 to
day 14.
Outcome
measures
Effect size
DVT: confirmed
by fibrinogen
uptake,
venograph or
doppler US
Int: 800/2474
Cont: 647/3134
p value: 0.0000
PE by scan,
angiogram, X-ray
or post-mortem
Int: 5/1921
Cont: 3/2230
(reported in 7
studies)
p value: 0.4838
Major Bleeds:
Int: 91/3197
Cont: 198/4063
p value: 0.0000
Proximal DVT
Int: 186/2474
Cont: 175/3134
(reported in 10
studies)
p value: 0.0701
Comments
Not reported: LoS,
QoL, PTS.
DRAFT FOR CONSULTATION
Oral anticoagulants vs LMWH
Bibliographic
reference
Colwell et al,
105
1999
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Intervention
Total: 3011 Type of surgery:
Elective total hip
Intervention arthroplasty
: n = 1495
Type:
Coumadin (adjusted
dose warfarin)
Dose:
Started at 7.5mg,
Control: n = Intervention: Mean adjusted to maintain
INR ratio between 2.0
age: 64.1±13.21
1516
to 3.0
(range: 19-99)
M/F:659/836
Timing:
Started between 48
Control: Mean age: hours preoperatively
(at the discretion of the
63.9±13.7 yrs
investigator) and 24
(range: 18-100)
hours postoperatively.
M/F: 678/838
Administered until
discharge.
Pre-existing risk
factors:
Significantly more
obese patients in
Additional nonenoxoparin arm
comparative
Int: 378/1376 had
2
prophylaxis:
BMI >30kg/m
Stockings permitted
(27.5%)
but not reported how
(BMI reported for
many patients
92% of this group)
received these
Control: 459/1420
2
had >30kg/m
(32.3%)
(BMI reported for
93.7% of this group)
p = 0.0055
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Type:
Enoxoparin
(LMWH)
Dose:
30mg
Timing:
Every 12 hours,
started within 24
hours
postoperatively
once haemostasis
(cessation of
active bleeding as
determined by the
investigator) had
been established
Administered until
discharge.
Additional noncomparative
prophylaxis:
Stockings
permitted but not
reported how
many patients
received these
314 of 648
Length of
follow up
Both
groups:
14 days
treatment,
3 month
follow up
Outcome
measures
Effect size
Symptomatic
DVT Confirmed
by US or
venography
Int: 44/1495
Control: 40/1506
p value: 0.6592
Symptomatic
DVT that
occurred in
hospital
Int: 15/1495
Control: 2/1506
p value: 0.0012
Symptomatic
DVT that
occurred after
discharge
Int: 29/1495
Control: 38/1506
p value: 0.3232
PE
Confirmed
by ventilation
perfusion scan or
pulmomary
angiography
Int: 9/1495
Control: 6/1506
p value: 0.4518
PE that occurred
in hospital
Int: 2/1495
Control: 1/1506
p value: 0.6235
PE that occurred
after discharge
Int: 7/1495
Control: 5/1506
p value: 0.5789
Both DVT & PE
Confirmed by one
of the above
methods
Int: 3/1495
Control: 9/1506
p value: 0.1452
Both DVT & PE
that occurred in
hospital
Int: 0/1495
Control: 1/1506
p value: 1.0000
Both DVT & PE
that occurred
after discharge
Int: 3/1495
Control: 8/1506
p value: 0.2257
Major bleeds
Int: 4/1495
Comments
Comments:
Results not
stratified by BMI.
No of VTEs by BMI:
BMI >30 = 48/111
(43.2%)
BMI <30 = 63/111
(56.8%)
No of VTEs out of
total no. of BMI
group
BMI >30 = 48/837
(5.73%)
BMI <30 = 63/1959
(3.22%)
Also reported:
Minor bleeding
Not reported:
PTS, LoS, QoL,
fatal PE
Funding:
No direct funding
for this study.
Indirect funding (i.e.
authors’ institution
funding) Rhone
Poulenc Rorer
Pharmaceuticals
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Length of
follow up
Outcome
measures
Effect size
Comments
Control: 9/1506
p value: 0.2658
Adverse events
(most commonly
reported were
fever, anemia,
nausea)
Int: 934/1495
Control: 987/1506
p value: 0.0870
Serious adverse
events
Int: 134/1495
Control: 167/1506
p value: 0.0128
Survival (specify)
Int: 1485/1495
Control: 1497/1506
p value: 0.8226
Evidence Table 31: Oral anticoagulants vs aspirin
Bibliographic
reference
Harris et al,
210
1974
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 187
randomised
(results for
168)
Interventio
n1: n = 5
Interventio
n2: n = 62
Control: n
= 51
Patients
characteristics
Type of surgery:
Total hip
replacement.
Duration of surgery
not reported.
Intervention1:
Mean age: 58.4 yrs
(s.d. not reported)
M/F:20/33
Intervention2:
Mean age: 55.5 yrs
(s.d. not reported)
Intervention
Intervention 1:
Type: adjusted dose
warfarin
Dose: 5mg
pre-op then adjusted
PTT 1.5 x control (or
for 18 secs)
Intervention 2:
Type: Low molecular
weight dextran 10%
w/v Dose: 500 ml
Duration – all
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Type: Aspirin
Dose: 1200 mg
started
preoperatively
Duration:
Continued until
the patient was
fully ambulatory
and ready for
discharge
Additional noncomparative
315 of 648
Length of
follow up
Outcome
measures
All groups: DVT Confirmed
until
by:
discharge
Venography,
radioiodine (I,
125) fibrogin
uptake test
Proximal DVT
Confirmed by:
Venography,
radioiodine (I,
125) fibrogin
uptake test
Effect size
Int1: 10/55
Int2: 14/62
Control: 18/51
p value: No
significant
differences between
groups.
Int1: 3/55
Int2: 8/62
Control: 10/51
p value: No
significant
differences between
groups.
Comments
Comments:
Fourth group of
patients received
LDUH. This arm
excluded due to a
change in dose
after 12 patients,
and then
discontinued after
20 patients. 2
patients in the
dextran group
received a clinical
diagnosis of PE.
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
M/F:35/26
Control:
Mean age: 57.7. yrs
M/F:21/29
Pre-existing risk
Factors: Obesity
(no significant
differences between
groups).
Intervention
interventions:
Continued until the
patient was fully
ambulatory and ready
for discharge
Additional noncomparative
prophylaxis: All
patients wore
stockings during and
post-surgery, leg
elevation, foot and
ankle exercises
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
prophylaxis: All
patients wore
stockings during
and post-surgery,
leg elevation, foot
and ankle
exercises
Length of
follow up
Outcome
measures
Length of
Hospital Stay
Effect size
Mean (all groups):
21 days. (No
significantdiff
between groups)
Comments
Multiple thrombi
were significantly
more common in
patients receiving
aspirin than either
warfarin or dextran.
Funding:
316 of 648
DRAFT FOR CONSULTATION
Oral anticoagulants vs aspirin
Bibliographic
reference
Mismetti et al,
365
2004
1 RCT
415
included
Study
Type
Evidenc
e level
Systemat 1+
ic review
No. of
patients
Total: 131
Int:65
Cont:66
Patients
characteristics
Type of surgery:
Orthopaedic (hip
replacement
surgery)
Intervention
Type:
OAC-adjusted
(Warfarin)
Comparison
Type:
Apsirin 650x2
Timing: Postoperative
Discharge or 3 weeks
Additional noncomparative
prophylaxis:
Not repoted
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
317 of 648
Length of
follow up
3 months
Outcome
measures
Effect size
Comments
DVT (Veno)
Int: 13/65
Cont: 27/66
p value: 0.0133
Not reported:
LoS, QoL, PTS
Proximal DVT
Int: 6/65
Cont: 7/66
p value: 1.0000
Funding: SanofiSynthelabo grant
PE
Int: 0/65
Cont: 1/66
p value: 0.0141
Major Bleeding
Int: 5/65
Cont: 1/66
p value: 0.1150
DRAFT FOR CONSULTATION
Oral anticoagulants vs aspirin
Bibliographic
reference
Lotke et al,
332
1996
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 388
(76
exclusions)
Interventio
n: n = 146
Control: n
= 166
Type of surgery:
Total hip or knee
arthroplasty
(&
Duration of surgery)
Intervention:
Mean age: 67.1 yrs
(s.d. not reported)
M/F:121/91 across
both groups
Control:
Mean age: 66.4 yrs
(s.d. not reported)
M/F:121/91 across
both groups
Intervention
Comparison
Type: adjusted dose
Type: Aspirin
warfarin Dose:
Dose: 325 mg
10mg pre-op then PTT twice daily
1.2 – 1.5 x control
Length of
follow up
Both
groups: 9
– 10 days
post-op. All
patients
Timing: 10mg eve
Timing: Begun on observed
before operation. Then day of admission
for 6
adjusted dose from 2nd
months.
Additional nonday post-op
comparative
prophylaxis:
Additional nonNot reported
comparative
prophylaxis:
Not reported
Outcome
measures
DVT Confirmed
by: Venography
(ipsalateral) on
th th
7 -9 day post-op
Int: 78/146
Control: 100/166
p value: Not
significant
Proximal DVT
Confirmed by:
Venography
(ipsalateral) on
th th
7 -9 day post-op
Int: 18/146
Control: 16/166
p value: Not
significant
Distal DVT
Confirmed by:
Venography
(ipsalateral) on
th th
7 -9 day post-op
Small Int: 42/146
Control: 45/166
p value: Not
significant
Large Int: 18/146
Control: 39/146
p value: Not
significant
Pre-existing risk
factors:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Effect size
318 of 648
PE
Confirmed
by: V/Q scan on
th
th
8 – 10 day postop
High probability
V/Q scan Int:
12/146
Control: 16/166
p value: Not
significant
Bleeding related
complications
Prolonged wound
drainage
(requiring
immobilisation,
attention in
rehabilitation for
wound problems,
or surgical
evacuation)
Int: 7/146
Control: 6/166
p value: Not
significant
Comments
Comments: No
difference in size or
location of clots
between study
groups. Patients
with TKR had 2.6 x
incidence of calf
DVT than THR.
Larger no of TKRs
in aspirin group, but
subgroup analyses
showed no
difference in DVT.
Not reported: Fatal
PE, PTS, QoL,
Survival, LoS
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Woolson et al, RCT
558
1991
Evidenc
e level
1+
No. of
patients
Total:
196
patients
217
operations
Int 1:
69 patients
and
operations
Int 2:
73 patients
and 76
operations
Cont:
70 patients
72
operations
(see
comments
)
Patients
characteristics
Type of surgery:
Total hip
replacement
(primary or revision)
Intervention 1
average age: 67.9
M/F 31/38
Intervention 1
average age: 66.3
M/F 27/66
Control
average age: 62.3
M/F 35/35
Pre-existing risk
factors:
Intervention:history
of DVT 10/69,
varicose veins 9/69
Control: history of
DVT 4/72, varicose
veins 5/72
Intervention
Intervention 1:
Type: Warfarin + IPCD
+ GCS
Dose: 7.5 or 10mg on
evening before
surgery, then adjusted
to maintain
prothrombin time
between 14 and 16
seconds.
Intervention 2:
Type: Thigh-length
Intermittent pneumatic
compression and
graduated elastic
stockings.
Comparison
Type:Aspirin +
IPCD + GCS
Dose: 650mg
twice per day
Timing:
Started evening
before surgery
and until
discharge.
Additional noncomparative
prophylaxis:
Not reported
Timing:
Warfarin started
evening before
surgery, IPCD and
stockings started at
surgery, both
continued until
discharge.
Length of
follow up
Intervention
until
discharge,
followed up
for 3
months
Outcome
measures
Effect size
Comments
Proximal DVT
Confirmed by
venography or
ultrasonograpy
Int 1: 6/69
Int 2: 9/76
Control: 7/72
not significant
Symptomatic PE
Confirmed by
ventilation
perfusion scan*
Int 1: 0/69
Int 2: 0/76
Control: 1/72
not significant
Total blood loss
(ml)
Int 1: 1564 (n = 69)
Int 2: 1539 (n = 76)
Control: 1595 (n =
72)
not significant
Out of 196 patients,
20 had bilateral hip
replacement, 1 had
both procedures in
the same operation,
18 had at least one
week between
procedures, 1 had
bilateral procedure
and a revision at a
later date. All of
these are included
in the total to make
217 operations
Total blood
replacement
(units)
Int: 2.8 (n = 69)
Int 2: 2.7 (n = 76)
Control: 2.9 (n =
72)
not significant
*DVT screened
whilst in hospital,
symptomatic PE
followed for 3
months.
LoS (days)
Int: 9 (n = 69)
Int 2: 10 (n = 76)
Control: 9 (n = 72)
not significant
Not reported:
All DVTs, QoL,
PTS, survival
Also reported:
Symptomatic DVTs
by operation,
prothrombin time
Funding:
reports: no
commercial funding
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
319 of 648
DRAFT FOR CONSULTATION
Evidence Table 32: Oral anticoagulants vs dextran
Bibliographic
reference
Mismetti2004
365
Study
Type
Evidenc
e level
Systemat 1+
ic review
No. of
patients
Total: 541
Patients
characteristics
Type of surgery:
Orthopaedic
Intervention
Type:
Warfarin
Int: 279
4 RCTs
included
29,161,212,378
Cont: 262
Timing:
Postoperative (3
studies)
Preoperative (1 study)
Ambulation (1 study)
3 weeks (1 study)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Type: Dextran
Timing:
Postoperative (3
studies)
Preoperative (1
study)
Additional noncomparative
prophylaxis:
Not reported
320 of 648
Length of
follow up
5-7 days (1
study)
11-14 days
(1 study)
3 weeks (1
study)
Outcome
measures
Effect size
DVT (Clinical,
confirmed by US
or veno
bilateral/FUT)
Int: 54/155
Cont: 56/129
p value: 0.1445
Major Bleeding
Int: 6/171
Cont: 1/156
p value: 0.1237
Proximal DVT
Int: 1/53
Cont: 6/37
p value: 0.0179
Death
Int: 4/164
Cont: 4/168
p value: 1.0000
Wound
haematoma
Int: 24/229
Cont: 23/207
p value: 0.2798
Comments
Not reported:
LoS, QoL, PTS
Funding: SanofiSynthelabo grant
DRAFT FOR CONSULTATION
Oral anticoagulants vs dextran
Bibliographic
reference
Harris et al,
210
1974
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 187
randomised
(results for
168)
Interventio
n1: n = 55
Interventio
n2: n = 62
Control: n
= 51
Patients
characteristics
Type of surgery:
Total hip
replacement.
Duration of surgery
not reported.
Intervention1:
Mean age: 58.4 yrs
(s.d. not reported)
M/F:20/33
Intervention2:
Mean age: 55.5 yrs
(s.d. not reported)
M/F:35/26
Control:
Mean age: 57.7. yrs
M/F:21/29
Intervention
Intervention 1:
Type: adjusted dose
warfarin
Dose: 5mg
pre-op then adjusted
PTT 1.5 x control (or
for 18 secs)
Intervention 2:
Type: Low molecular
weight dextran 10%
w/v Dose: 500ml
daily for 3 days and
500ml on alternate
days until discharge
Duration – all
interventions:
Continued until the
patient was fully
ambulatory and ready
for discharge
Comparison
Type: Aspirin
Dose: 1200 mg
Duration:
Continued until
the patient was
fully ambulatory
and ready for
discharge
Additional noncomparative
prophylaxis: All
patients wore
stockings during
and post-surgery,
leg elevation, foot
and ankle
exercises
Pre-existing risk
factors: Obesity (no
Additional nonsignificant
differences between comparative
prophylaxis: All
groups).
patients wore
stockings during and
post-surgery, leg
elevation, foot and
ankle exercises
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
Outcome
measures
All groups: DVT Confirmed
until
by:
discharge
Venography,
radioiodine (I,
125) fibrogin
uptake test
Effect size
Int1: 10/55
Int2: 14/62
Control: 18/51
p value: No
significant
differences between
groups.
Proximal DVT
Confirmed by:
Venography,
radioiodine (I,
125) fibrogin
uptake test
Int1: 3/55
Int2: 8/62
Control: 10/51
p value: No
significant
differences between
groups.
Length of
Hospital Stay
Mean (all groups):
21 days. No
significant
differences between
groups
Comments
Comments:
Fourth group of
patients received
LDUH. This arm
excluded due to a
change in dose
after 12 patients,
and then
discontinued after
20 patients. 2
patients in the
dextran group
received a clinical
diagnosis of PE.
Multiple thrombi
were significantly
more common in
patients receiving
aspirin than either
warfarin or dextran.
Funding: Not
reported
321 of 648
DRAFT FOR CONSULTATION
Oral anticoagulants vs dextran
Bibliographic
reference
Lambie et al,
308
1970
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 80
Interventio
n: n = 40
Control: n
= 40
Patients
characteristics
Type of surgery:
Major
gynaecological
surgery
(hysterectomy or
pelvic floor repair).
Intervention
Type: Adjusted dose
warfarin Dose: 30
mg pre-op, then
adjusted to maintain
PTT 2 – 2.5 x control
Timing: 30mg 36
Intervention: Mean hours post-op, then
adjusted dose. Not
age: 57.9 yrs (s.d.
reported when stopped
not reported). All
female
Additional nonControl: Mean age: comparative
prophylaxis: all
55.9 yrs (s.d. not
reported). All female patients received
potassium iodide preop, and for 2 weeks
Pre-existing risk
post-op. Normal ward
factors: all were
routine of visit by
high-risk patients
due to either 1. age physio to encourage
> 45 yrs and obese, leg movement and
or 2. previous history breathing exercises
of VTE or gross
varicose veins.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Type: Dextran 70
Dose: 7 ml/kg
body weight
during op, then
3.5ml/kg daily
Timing: 7ml/kg
periop, then
3.5kg/ml for 3
days post-op.
Additional noncomparative
prophylaxis: all
patients received
potassium iodide
pre-op, and for 2
weeks post-op.
Normal ward
routine of visit by
physio to
encourage leg
movement and
breathing
exercises
322 of 648
Length of
follow up
Outcome
measures
Effect size
Int: 12/40
Scanning
DVT Confirmed
upto day 10 by: Radioiodine (I, Control: 4/40
p value: 0.0482
125) fibrogin
uptake test. Scan
carried out
immediately postop and repeated
daily for 8-10
days.
Comments
Comments:
Patients were
stratified according
to surgical
procedure
(hysterectomy or
pelvic floor repair)
and then
randomised. DVT
was also classified
as major/minor
according to
location, size, both
legs, associated
with PE.
Not reported:
Proximal DVT, PE,
PTS, Bleeding
complications, QoL,
survival, LoS,
funding.
DRAFT FOR CONSULTATION
Evidence Table 33: Oral anticoagulants vs heparinoids
Bibliographic
reference
Mismetti 2004
365
2 RCTs
112,186
included
Study
Type
Evidenc
e level
Systemat 1+
ic review
No. of
patients
Total:
777
Interventio
n: 378
Control:
373
Patients
characteristics
Type of surgery:
Orthopaedic
Intervention
Type:
Warfarin
Comparison
Type:
Danaparoid
Timing:
Timing:
Preoperative (2
Preoperative (2
studies)
studies)
9 days (1 study)
8-10 days or discharge
if earlier(1 study)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
323 of 648
Length of
follow up
9 days (1
study)
Outcome
measures
DVT (FUT/Veno
bilatieral)
Effect size
Int: 89/328
Cont: 42/331
p value: 0.0000
Comments
Not reported:
LoS, QoL, PTS
Funding: SanofiSynthelabo grant
3 months (1
study)
Proximal DVT
Int: 8/197
Cont: 3/199
p value: 0.1389
PE
Int: 2/378
Cont: 0/373
p value: 0.4994
Death
Int: 7/378
Cont: 2/373
p value: 0.0153
Major Bleeding
Int: 12/378
Cont: 15/373
p value: 0.2047
Wound
haemotoma
Int: 4/378
Cont: 6/373
p value: 0.5437
DRAFT FOR CONSULTATION
Evidence Table 34: Danaparoid vs no prophylaxis
Bibliographic
reference
Hoek et al
232
1992
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Intervention
Total: 196
Type of surgery:
Total hip
replacement
(&
Duration of surgery)
Type: Heparinoid
(Lomoparan) Dose:
750 anti-factor Xaunits
Intervention Intervention: Mean
Timing: Begun 15-45
age: 67.2±10 yrs
: n = 97
mins pre-op. Second
Control: n = M/F:21/76
dose 6hrs post-op,
99
then repeated twice
daily until 10th post-op
day.
Control: Mean age:
218
randomised 70.1±9 M/F:26/73
. 198
patients
Additional nonPre-existing risk
treated as
comparative
factors: none
perprophylaxis:
reported
protocol.
Not reported
Venograms
not
available
for 2
patients
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Placebo
Timing: Same
administration
schedule as
heparinoid
Length of
follow up
Both
groups: 8
weeks
Outcome
measures
Effect size
DVT Confirmed
by: Bilateral
venography on
th
10 (±2) post-op
day
Int: 15/97
Control: 56/99
p value: <0.0001
Proximal DVT
Confirmed by:
Bilateral
venography on
th
10 (±2) post-op
day
Int: 8/97
Control: 25/99
p value: <0.005
(Significant)
Symptomatic PE Int: 0/97
Confirmed by: V/Q Control: 0/99
scan
p value: N/A
Int: 0/97
Major bleed:
Control: 0/99
When
p value: N/A
haemorrhage
occurred in a
critical organ e.g.
brain, eye, kidney,
or when
haematoma
formation at the
surgical site
necessitated
reoperation
324 of 648
Minor bleeding
Int: 6/97
Control: 0/99
p value: <0.05
Survival
Int: 96/97
Control: 99/99
p value: 0.4949
Comments
Comments: Study
also reports no of
patients with distal
VT only, combined
proximal and distal,
and bilateral deep
vein thromboses.
All significantly
lower in heparinoid
group. 3/82
heparinoid patients
had developed
DVT at 8 weeks (1
of whom died of a
PE)
Also reported:
Units of red cells
transfused, total
drain fluid
Not reported: QoL,
LoS, funding
DRAFT FOR CONSULTATION
Evidence Table 35: Danaparoid vs dextran
Bibliographic
reference
Bergvist et al
53
1991
Study
Type
Multicent
re RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 247
Intervention
: n = 117
Control: n =
130
Type of surgery:
Hip fracture surgery
(fracture sustained
<24hrs prior to
hospital admission.
Scheduled for
surgery with 72hrs)
(patients
receiving
perDuration of
protocol
prophylaxis surgery:
Int: 66±33 min Cont:
)
67±33 min
(308
Intervention: Mean
patients
randomised age: 77±11 yrs
M/F:28/72
. 19
withdrawn
from study. Control: Mean age:
77±11yrs
42 did not
receive per- M/F:18/82
protocol
prophylaxis Pre-existing risk
factors: None
)
reported
Intervention
Comparison
Type: Heparinoid (Org Type: Dextran 70
10172)
Dose: 750 anti-Xa
units
Timing: Begun as
soon as possible after
hospital admission and
repeated 2x daily until
10-12th post-op day
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Timing: 500 ml
immediately after
enrolement.
Repeated every
nd
2 day until
surgery. 500 ml
during op, and
st
500 ml on 1 and
nd
2 post-op days
Length of
follow up
Both
groups: 8
weeks ±2
days
Outcome
measures
DVT Confirmed
by: Bilateral
ascending
venography on
post-op days 1012 (denominators
do not include
patients for whom
no DVT results
are available)
Per-protocol
analysis:
Int: 14/107
Control: 40/115
p value: <0.001
Symptomatic PE
(non-fatal)
Confirmed by: V/Q
scan, angiogram
or autopsy
Int: 1/117
Control: 2/130
p value: Not
reported
Fatal PE
Confirmed by:
Autopsy
Int: 0/117
Control: 3/130
p value: NR
Intraoperative
bleeding:
(median, range)
calculated by
anaesthetist from
amounts in swabs
325 of 648
Effect size
Intention to treat:
Int: 14/139
Control: 43/138
p value: <0.001
Comments
Multicentre trial
based in 3
hospitals. Patients
received both FUT
and venography.
Where venography
could not be
performed, DVT
diagnosis was
made based on
FUT alone.
Also reported:
No. of patients
requiring
transfusions
Not reported:
Proximal DVT,
PTS, QoL, LoS,
Int: 200 (0-1800) ml
funding
Control: 200 (02300) ml
p value: Not
significant
No of
transfusions on
post-op day:
Int: 33/117
Control: 35/130
p value: Not
significant
No of
transfusions
after surgery:
Int: 31/117
Control: 53/130
p value: <0.01
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Length of
follow up
Outcome
measures
Effect size
Int: 17
All cause
mortality (unclear Control: 9
p value: NR
whether these
figures are preprotocol or
intention to treat)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
326 of 648
Comments
DRAFT FOR CONSULTATION
Evidence Table 36: Danaparoid vs low molecular weight heparin
Bibliographic
reference
Study
Type
Bergqvist et al Multicent
44
1999
re RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 197
Intervention
: n = 65
Compariso
n 1: n = 66
Compariso
n 2: n = 66
Type of surgery:
Hip fracture surgery
(fracture sustained
<24hrs prior to
hospital admission.
Scheduled for
surgery with 48hrs)
Duration of
surgery:
Int: 74±38 min
Comp1: 69±33 min
Comp2: 70±26 min
Intervention
Comparison
Type: Danaparoid
Dose: 750 anti-Xa
units
Comparison1:
LMWH
Enoxaparin
Dose: 20mg
Timing: Begun at least then 40 mg
1 hr pre-op (2x daily
until op), then 2x daily Timing: 20mg at
until 11th post-op day least 2 hrs pre-op
(2X daily until op),
then 40 mg daily
Additional nonuntil 11th day
comparative
prophylaxis:
Comparison2:
Not reported
LMWH Dalteparin
Intervention: Mean
Dose: 2500 IU
age: 79±12 yrs
M/F:16/49
Timing: Begun at
least 2 hrs pre-op
Comparison1:
(2X daily until op),
Mean age: 77±11yr
then twice daily
M/F:18/48
until 11th day
Comparison2:
Mean age: 76±10
yrs M/F:14/52
Pre-existing risk
factors: History of
VTE, history of
obesity
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
327 of 648
Length of
follow up
Outcome
measures
All groups:
2 months
(for
survival)
DVT Confirmed
by: Bilateral
venography on 911th day of
treatment
Int: 3/53
Comp1: 8/52
Comp2: 5/57
p value: No
significant
differences between
groups
Proximal DVT
Confirmed by: as
above
Int: 2/53
Comp1: 2/52
Comp2: 3/57
p value: No
significant
differences between
groups
PE
Confirmed
by: Clinical
suspicion
investigated with
V/Q scan
Int: 0/65
Control: 0/66
Comp2: 0/66
p value: Not
significant
Major bleeding:
leading to death or
reoperation,
occurring
intracranially or
into major organs
(e.g. lung, eye,
adrenals) or when
associated with a
decrease in
haemoglobin of
>2mmol/L within
72hr
Int: 1/65
Control: 2/66
Comp2: 1/66
p value: Not
significant
Effect size
Comments
Comments:
Patients
randomised to 3
study groups –
Danaparoid,
Enoxaparin or
Dalteparin. Results
from LMWH groups
have been grouped
together in metaanalysis. Study
conducted at 4
centres.
Not reported: PTS,
QoL, Los
Funding: Swedish
Medical Research
Council
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Length of
follow up
Outcome
measures
Survival at 2 mo:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
328 of 648
Effect size
Int: 60/65
Comp1: 64/66
Comp2: 66/66
p value: Not
reported
Comments
DRAFT FOR CONSULTATION
Evidence Table 37: Danaparoid vs unfractionated heparin
Bibliographic
reference
Gallus et al
177
1993
Study
Type
Multicentre
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 513
Type of surgery:
Cancer surgery
Intervention (intra-abdominal or
intrathoracic)
(&
: n = 257
Control: n = Duration of surgery)
256
Protocol
violations in Intervention: Mean
60 patients. age: 64.3±10.1 yrs
M/F:163/94
No DVT
outcome
Control: Mean age:
measure
66.0±10.4 yrs
for 23
M/F:158/98
patients
Pre-existing risk
factors: Malignancy
Intervention
Comparison
Type: Heparinoid
(Orgaran) Dose:
750 anti-factor Xa
Type:
Unfractionated
heparin Dose:
5000IU
Timing: Begun 1-2 hrs
pre-op then 2 x daily
until at least 6th postop day
Timing: Begun 12 hrs pre-op then
2 x daily until at
least 6th post-op
day
Additional noncomparative
prophylaxis: Patients
at two centres received
electrical calf
stimulation during
operation
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Additional noncomparative
prophylaxis:
Patients at two
centres received
electrical calf
stimulation during
operation
329 of 648
Length of
follow up
Both
groups: 46 weeks
postdischarge
Outcome
measures
DVT Confirmed
125
by: I FUT on
alternate days. *
Effect size
Intention to treat:
Int: 25/241
Control: 37/249
p value: Not
significant
Symptomatic PE Int: 1/241
Confirmed by: V/Q Control: 0/249
scan
p value: Not
significant
Fatal PE
Confirmed by:
autopsy
Int: 1/241
Control: 0/249
p value: Not
significant
Patients with
bleeding*
Int: 23/257
Control: 27/256
p value: Not
significant
Reoperation for
bleeding:
Int: 3/257
Control: 4/256
p value: Not
significant
Intraoperative
blood loss:
Int: 573±644 ml
Control: 615±714
p value: Not
significant
“excessive”
intraoperative
bleeding*
Int: 15/257
Control: 27/256
p value: Not
significant
Comments
Comments:
* Per-protocol
analysis also
revealed no
significant diffs
(results not
reported)
Not reported:
Proximal DVT,
PTS, QoL, LoS
Funding: Orgaran
International
(Netherlands)
* “Excessive”
bleeding estimated
by surgeons
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
330 of 648
Length of
follow up
Outcome
measures
Effect size
“excessive”
postoperative
bleeding*
Int: 10/230
Control: 14/234
p value: Not
significant
Survival (specify)
Int: 235/257
Control: 240/256
p value: Not
significant
Comments
DRAFT FOR CONSULTATION
Danaparoid vs unfractionated heparin
Bibliographic
reference
Leyvraz et al
326
1992
Study
Type
Multicent
re RCT
Evidenc
e level
1+
No. of
patients
Total: 309
randomised
Intervention
: n = 154
Control: n =
155
Patients
characteristics
Type of surgery:
Total hip
replacement
Duration of surgery:
Mean and range
Int: 114 (60-295) min
Venograms Cont: 108 (50-220)
min
not
available
for 19
patients. 6 Intervention: Mean
age: 66±11 yrs
protocol
M/F:42/58
violations
Intervention
Type: Heparinoid
(Lomoparan)
Dose: 750 anti Xa
Comparison
Type: UFH + DHE
Dose: 5000IU
+0.5
dihydroergotamine
(DHE)
Timing: Begun 2hrs
Timing: Begun
pre-op and repeated
twice daily until 10 (±1) 2hrs pre-op and
repeated twice
days post-op
daily until 10 (±1)
days post-op
Additional noncomparative
prophylaxis:
Not reported
Control: Mean age:
67±11 yrs
M/F:29/71
Pre-existing risk
factors: Varicose
veins, previous VTE
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
331 of 648
Length of
follow up
Both
groups:
Clinical
evaluation
4-7 weeks
after
venography
(during FU
period type
and
duration of
anticoagula
nt
treatment
varied
between
centres).
Outcome
measures
Effect size
Int: 25/145
DVT Confirmed
by: Doppler US on Control: 44/139
p value: 0.007
1,3,6,9 post-op
day. Bilateral
venography on
th
10 (±1) post-op
day
Proximal DVT
Confirmed by: As
above
Int: 7/145
Control: 9/139
p value: Not
significant
Symptomatic PE
Confirmed by V/Q
scan
Int: 1/145
Control: 1/139
p value: Not
significant
Major bleeding:
(prophylaxis
interrupted)
Int: 1/153
Control: 1/150
p value: Not
significant:
Moderate
bleeding:
(prophylaxis
continued)
Int: 1/153
Control: 2/150
p value: Not
significant
Minor bleeding:
Sound
haematomas
and/or oozing
Int: 83/153
Control: 79/153
p value: Not
significant
No. of patients
requiring
transfusion on
day of operation
Int: 149/153
Control: 136/150
p value: 0.03
Comments
Comments: Set in
three orthopaedic
centres. No patient
developed
thrombocytopenia
during prophylaxis
period. 2 patients
treated for DVT
developed
thrombocytopenia
rd
th
on 3 and 11 day
of heparin
treatment.
Also reported:
Intraoperative and
postoperative blood
loss
Not reported: PTS,
QoL, survival, LoS
6 patients excluded
from bleeding
analysis due to
protocol violation
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Length of
follow up
Outcome
measures
No. of patients
requiring
transfusion after
operation
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
332 of 648
Effect size
Int: 50/153
Control: 41/139
p value: Not
significant
Comments
DRAFT FOR CONSULTATION
Evidence Table 38: Danaparoid vs aspirin
Bibliographic
reference
Gent et al
185
1996
Study
Type
Multicentre
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 251
Intervention
: n = 125
Control: n =
126
Type of surgery:
Hip fracture surgery
(& Duration of
surgery)
Intervention
Type: Heparinoid
(Orgaran) Dose: 750
anti-factor Xa units
Timing: Begun 1224hrs post-op and
Intervention: Mean repeated twice daily for
age: 76.6 yrs (range 14 days or until
discharge
26-94)
M/F:23/102
Additional noncomparative
Control: Mean age: prophylaxis: None
reported
76.6 yrs (range 2597) M/F:24/102
Comparison
Type: Aspirin
Dose: 100 mg
Timing: Begun
12-24hrs post-op
and repeated
twice daily for 14
days or until
discharge
Additional noncomparative
prophylaxis:
None reported
Pre-existing risk
factors: Cancer
Length of
follow up
Both
groups: 3
months
Outcome
measures
Effect size
DVT Confirmed
125
by: I FUT daily
th
until 14 day or
discharge.
Positive result
confirmed by
venography. All
patients
underwent
bilateral
venography prior
to discharge.
178 patients had
evaluable
venograms
Proximal DVT
Confirmed by: as
above (171
patients had
evaluable
venograms)
Int: 6/88
Control: 11/83
p value: Not
significant
Int: 25/90
Control: 38/88
p value: 0.03
Int: 0/125
Control: 0/126
p value: N/A
Major bleeding* : Major bleeding:
Int: 1/125
Control: 4/126
p value: 0.1
Minor bleeding:
Overt but not
meeting the
criteria above
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
333 of 648
Comments: Well
conducted study.
DVT and PE
analysed together
(as total VTE) and
had to be
separated out.
Not reported: PTS,
QoL
:
Symptomatic PE Int: 0/125
Confirmed by: V/Q Control: 1/126
p value: 1.0000
scan, angiogram
or at autopsy.
Fatal PE
Confirmed by:
autopsy
Comments
Int: 1/125
Control: 4/126
p value: 0.1
* Major bleeding:
overt and
associated with a
fall in haemoglobin
level of 20g/L or
more; led to
transfusion of
≥2units of blood; or
if it was
retroperitoneal,
intraocular, or
intracrianial
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
334 of 648
Length of
follow up
Outcome
measures
Effect size
All cause
mortality (at 3
mos)
Int: 5/125
Control: 8/126
p value: 0.5707
Length of
Hospital Stay
Int: 11 days (range
5-15)
Control: 9.7 days
(1-17)
p value: Not
reported
Comments
DRAFT FOR CONSULTATION
Evidence Table 39: Dextran vs no prophylaxis
Bibliographic
reference
Study
Type
Evidenc
e level
Roderick et al, Systemat 1+
430
2005
ic Review
13 RCT
studies
included
48,50,90,149,198,222,2
41,253,254,259,338,52
6,542
No. of
patients
1573
Patients
characteristics
Populations of
studies:
3 general surgery
6 orthopaedic
1 urological
3 mixed surgical
studies.
Intervention
Comparison
Dextran 70 (500ml) in No prophylaxis 8
studies
8 studies
Dextran 40 (500ml) in Placebo 5 studies
3 studies
Dextran 40/70 (500ml)
in 1 study
Dextran lmw (500ml) in
1 study
Timing
First dose:
Perioperatively for 7
studies
At anaesthesia for 5
studies
Postoperatively for 1
study
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
335 of 648
Length of
follow up
Outcome
measures
Varied from
7 days to
14 days, or
until
discharge
DVT (confirmed
by systemic
venography,
fibrinogen labelled
iodine,
plethysmography,
duplex US
scanning,
thermography or
labelled plasmin)
Int: 180/794
Cont: 214/722
(from 13 studies)
p value: 0.0023
PE (confirmed by
ventilation/perfusi
on lung scans or
symptomatic PE
confirmed by
ventilation/perfusi
on lung scans,
angiography or
post-mortem)
Int: 8/71
Cont: 10/69
(from 2 studies)
p value: 0.6205
Proximal DVT
Int: 16/238
Cont: 21/243
(from 4 studies)
p value: 0.4951
Major bleeds
Int: 0/190
Cont: 0/195
(from 5 studies)
p value: N/A
Effect size
Comments
DRAFT FOR CONSULTATION
Dextran vs no prophylaxis
Bibliographic
reference
Bonnar and
67
Walsh, 1972
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total:
260
Interventio
n: n = 120
Control: n
= 140
Patients
characteristics
Type of surgery:
Abdominal and
vaginal
hysterectomy for
benign conditions
(& Duration of
surgery)
Intervention
Comparison
Type: Dextran 70
Dose: 6% w/v
Dextrans (in 1L sodium
chloride injection). 2 x
500 ml
Placebo: 1L of
compound sodium
lactate injection
BP
Timing: 500 ml
during operation.
Timing: 500 ml during Second 500ml
dose started prior
Intervention: Mean operation. Second
to leaving theatre.
age: 47.5 ± 10.1 yrs 500ml dose started
prior to leaving theatre. Full dose received
All female
within 6hrs of start
Full dose received
of operation.
Control: Mean age: within 6hrs of start of
operation.
45.7 ± 9.8 All
Additional nonfemale
comparative
Additional nonprophylaxis: 120
comparative
Pre-existing risk
mg potassium
prophylaxis: 120 mg
factors: Weight,
iodide. Begun 1
potassium iodide.
previous history of
day pre-op and
Begun 1 day pre-op
VTE, OACs (no
continued for 3
and continued for 3
significant
weeks
differences between weeks
groups).
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
336 of 648
Length of
follow up
Outcome
measures
Fibrogen
uptake test
upto 7
days
postoperat
ively.
DVT Confirmed
by: Bilateral
Radioiodine (I,
125) fibrogin
uptake test, 4-6
hours post-op and
on days 1,3,5,7
post-op
Effect size
Int: 1/120
Control: 15/140
p value: <0.01
(Significant)
Int: 0/120
Proximal DVT
Control: 4/150
Confirmed by:
p value: 0.1315
Bilateral
Radioiodine (I,
125) fibrogin
uptake test, 4-6
hours post-op and
on days 1,3,5,7
post-op
Bleeding related
complications
No. of patients
requiring blood
transfusion during
op or first 24hrs
post-op
Int: 13/120
Control: 11/140
p value: not
significant.
Comments
Comments: Poor
method of
randomisation (by
birth year) but study
was placebocontrolled and
double-blind. One
patient in control
group who had
Proximal DVT (and
consequent
initiation of
anticoagulation)
developed a small
PE
Not reported: PE,
PTS, QoL, survival,
LoS, funding
DRAFT FOR CONSULTATION
Dextran vs no prophylaxis
Bibliographic
reference
Study
Type
Stephenson et RCT
484
al 1973
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 80
Type of surgery:
Elective major
Interventio abdominal
n: n = 34
Control: n Intervention: Mean
age: 57.9±12 yrs
= 46
M/F:17/17
Control: Mean age:
56.9±11.6 yrs
M/F:19/27
Intervention
Type: Dextran
Dose: Dex 70
Comparison
Nil prophylaxis
Timing: 500 ml on day
of op and 1st post-op
day
Additional noncomparative
prophylaxis:
Not reported
Length of
follow up
Outcome
measures
Both
groups:
10-12 days
post-op
DVT Confirmed
125
by: I FUT daily
th
until 10 post-op
th
day (or 12 if
patient developed
thrombus)
Effect size
Int: 10/34
Control: 16/46
p value: 0.6 < p <
0.7
Comments
Paitients with
thrombosis whose
leg counts fell
dramatically were
investigated for PE
with lung scan,
which were positive
in 3 dex and 5 nil
patients (and
symptomatic in 4/5
nil patients only)
Not reported:
Proximal DVT,
PTS, Bleeding,
QoL, survival, LoS.
Pre-existing risk
factors: Malignancy
Funding: Medical
Research Council
(UK) grant
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
337 of 648
DRAFT FOR CONSULTATION
Evidence Table 40: Dextran as an adjuvant
Bibliographic
reference
Study
Type
Evidenc
e level
Roderick et al, Systemat 1+
430
2005
ic Review
No. of
patients
Total: 672
(5 studies)
5 RCTs
17,459,47
included
3,493,516
Patients
characteristics
Populations of
studies:
1 general surgery
3 orthopaedic
1 mixed surgical
studies.
Intervention
Dextran 70 (500ml) in
2 studies
Dextran 40 (500ml) in
3 studies
Comparison
No prophylaxis 4
studies
Placebo 1 studies
Timing
First dose:
Perioperatively for 3
studies
At anaesthesia for 1
studies
Postoperatively for 1
study
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
338 of 648
Length of
follow up
Outcome
measures
Varied from
7 days to
11 days, or
until
discharge
DVT (confirmed
by systemic
venography,
fibrinogen labelled
iodine)
Int:62/330
Cont:112/342
(from 5 studies)
p value: 0.0000
PE (confirmed by
ventilation/perfusi
on lung scans or
symptomatic PE
confirmed by
ventilation/perfusi
on lung scans,
angiography or
post-mortem)
Int: 8/230
Cont: 16/230
(from 3 studies)
p value: 0.1433
Proximal DVT
Int: 14/71
Cont: 23/81
(from 1 studies)
p value: 0.2573
Major bleeds
Int: 19/204
Cont: 9/216
(from 3 studies)
p value: 0.0491
Effect size
Comments
DRAFT FOR CONSULTATION
Evidence Table 41: Dextran vs low molecular weight heparin
Bibliographic
reference
Study
Type
Evidenc
e level
Roderick et al, Systemat 1+
430
2005
ic Review
5 RCTs
included
144,347,394,546
No. of
patients
1439
Patients
characteristics
Populations of
studies:
1 general surgery
4 orthopaedic
Intervention
Comparison
Dextran 70 (500ml) in
5 studies
Dextran 70 (500ml)
plus placebo LMWH in
1 study
Low molecular
weigth heparin
50mg 1x/day 2
studies
3000 IU 1x/day 1
study
2500 units 2x/day
1 study
20mg 1x/day plus
placebo LMWH 1
study
Timing
First dose:
Perioperatively for 4
studies
At anaesthesia for 1
study
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Timing
Started
preoperatively
339 of 648
Length of
follow up
Outcome
measures
Varied from
6 days to
14 days, or
until
discharge
DVT (confirmed
by systemic
venography, or
fibrinogen labelled
iodine)
Int: 151/497
Cont: 90/499
(from 5 studies)
p value: 0.0000
PE (confirmed by
scan)
Int: 7/386
Cont: 6/391
(from 4 studies)
p value: 0.7876
Proximal DVT
Int: 12/497
Cont: 9/499
(from 5 studies)
p value: 0.8285
Major bleeds
Int: 0/441
Cont: 0/448
(from 4 sudies)
p value: N/A
Effect size
Comments
Not reported: LoS,
QoL and PTS.
DRAFT FOR CONSULTATION
Evidence Table 42: Dextran vs unfractionated heparin
Bibliographic
reference
Study
Type
Evidenc
e level
Roderick et al, Systemat 1+
430
2005
ic Review
No. of
patients
1439
(5 studies)
10 RCT
included
48,50,198,236,241,338,
513,516,542,548
Patients
characteristics
Populations of
studies:
3 general surgery
2 orthopaedic
1 gynaecological
1 vascular
3 mixed surgical
studies.
Intervention
Dextran 70 (500ml) in
6 studies
Dextran 60 (500ml) in
1 study
Dextran 40 (500ml) in
3 studies
Timing
First dose:
preoperatively for 1
study
perioperatively for 7
studies
at anaesthesia for 2
studies
Comparison
Unfractionated
heparin
5000 IU 2x/day 8
studies
5000 IU 1x/day 1
study
4000 IU 2x/day 1
study
Timing
Started
preoperatively
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
340 of 648
Length of
follow up
Outcome
measures
Varied from
7 days to
14 days, or
until
discharge
DVT (confirmed
by systemic
venography,
fibrinogen labelled
iodine,
plethysmography,
duplex US
scanning,
thermography or
labelled plasmin)
Int:130/681
Cont:81/660
(from 10 studies)
p value: 0.0010
PE (confirmed by
ventilation/perfusi
on lung scans or
symptomatic PE
confirmed by
ventilation/perfusi
on lung scans,
angiography or
post-mortem)
Int: 5/226
Cont: 3/213
(from 4 studies)
p value: 0.7250
Proximal DVT
Int: 17/316
Cont: 8/311
(from 5 studies)
p value: 0.1010
Major bleeds
Int: 4/589
Cont: 11/586
(from 8 studies)
p value: 0.0743
Effect size
Comments
Not reported: LoS,
QoL, PTS
DRAFT FOR CONSULTATION
Dextran vs unfractionated heparin
Bibliographic
reference
Barber et al,
29
1977
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 70
Interventio
n: n = 51
Control: n
= 19
Patients
characteristics
Type of surgery:
Total hip
replacement
Duration of surgery
not reported
Intervention: Of
128 patients
included in entire
trial, mean age 65.5
yrs (range 39-85),
M/F 18/23
Control: Of 128
patients included in
entire trial, mean
age 65.5 yrs (range
39-85), M/F ratio
8/11
Intervention
Type: Dextran70
Dose: 1000 ml, then
500ml
Additional noncomparative
prophylaxis: Patients
spent 1 hr each
morning and afternoon
performing active
exercises under
supervision of
physiotherapist
Comparison
Type: LDUH
Dose: 5000IU
Timing
Started evening
before surgery
and given 2x/day
for 3 weeks
Additional noncomparative
prophylaxis:
Patients spent 1
hr each morning
and afternoon
performing active
exercises under
supervision of
physiotherapist
Pre-existing risk
factors: Patients
with past history of
VTE or malignancy
excluded.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
341 of 648
Length of
follow up
Both
groups:
until
discharge
Outcome
measures
DVT Confirmed
by: Bilateral
Radioiodine (I,
125) fibrogin
uptake test, daily
until patient
mobile (11-14th
post-op day)
Effect size
Comments
Comments: Study
Int: 26/51
also had an OAC
Control: 10/19
p value: > 0.05 Not group.
Mismetti2004
significant
reports OAC vs
LDUH and OAC vs
Dex comparisons.
Only 19 patients in
LDUH group.
Appears to have
been discontinued
due to high
incidence of PE in
this group (3 – one
fatal).
DRAFT FOR CONSULTATION
Dextran vs unfractionated heparin
Bibliographic
reference
Fredin et al
167
1983
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 207
Type of surgery:
Total hip
Interventio replacement
n: n = 114 Duration of surgery:
Control: n 114±42 mins
= 93
Intervention: Mean
age: NR M/F:33/81
Control: Mean age:
NR M/F:34/59
Intervention
Type: Dextran
Dose: Dex 70
Timing: 1000 ml on
day of op, then 500 ml
st
rd
on 1 and 3 post-op
day. Patients with
>2000ml intraop blood
loss were given
additional 500 ml on
nd
2 post-op day
Comparison
Type:
Unfractionated
heparin +
dihydroergotamine
Dose: 5000 IU +
0.5mg DHE
Timing: Begun
2hrs pre-op and
repeated 2x daily
for 10 days
Additional noncomparative
prophylaxis:
Not reported
Length of
follow up
Scanned
upto 14
days
postoperati
vely
Outcome
measures
Effect size
DVT Confirmed
by: Venography
on operated leg
only 10-14 days
post-op
Int: 49/114
Control: 41/93
p value: Not
significant
PE
Confirmed
by: All patients
had V/Q scan on
10-14th post-op
day
Int: 22/114
Control: 20/93
p value: Not
significant
Comments
Paper does not
report how many
patients were
randomised but not
included in
analysis. Unequal
nos in groups
suggests may have
been some
withdrawals. AT III
levels measured
pre- and post-op.
Sub-normal levels
not associated with
higher frequency of
VTE
Not reported:
Proximal DVT,
PTS, Bleeding,
QoL, survival, LoS,
funding
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
342 of 648
DRAFT FOR CONSULTATION
Dextran vs unfractionated heparin
Bibliographic
reference
McCarthy et
353
al, 1974
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total:
132
Interventio
n: n = 68
Control: n
= 64
Type of surgery:
Gynaecological
(major vaginal or
abdominal surgery).
Duration of surgery
not reported.
Intervention
Type: Dextran 70
Dose: 500 ml
Timing: 500 ml after
induction of
anaesthetic. 500 ml
within first 24hrs postIntervention: Mean op
age: 52.7 ± 9.6 yrs.
Additional nonAll female
comparative
Control: Mean age: prophylaxis: 150 mg
potassium iodine orally
50.8 ± 8.6 All
at least 24hrs pre-op
female.
and daily for 3 weeks.
Mobilised 24-48 hrs
Pre-existing risk
post-op and
factors: varicose
encouraged by physio
veins, cancer, past
to perform regular leg
history of VTE. No
and chest exercises.
significant diffs
between groups
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Type: LDUH
Dose: 5000 IU
Timing: Begun 2
hrs pre-op and
repeated every 12
hrs for 7 days.
Additional noncomparative
prophylaxis: 150
mg potassium
iodine orally at
least 24hrs pre-op
and daily for 3
weeks. Mobilised
24-48 hrs post-op
and encouraged
by physio to
perform regular
leg and chest
exercises.
343 of 648
Length of
follow up
Both
groups: 7
days
Outcome
measures
Effect size
Int: 11/68
DVT Confirmed
by: Radioiodine (I, Control: 7/64
p value: 0.4519
125) fibrogin
uptake test 3-4
times at not > than
48 hr intervals.
Int: 4/68
Wound
haematoma (none Control: 7/64
p value: > 0.4 Not
were major).
significant
Mean blood loss
(in 45 Dextran and
39 LDUH
patients).
Int: 216.5 ml
Control: 217.5 ml
p value: Not
significant
Comments
Comments:
Patients were
randomly allocated
to one of two
treatment groups
using the terminal
digit of their
hospital bureau
number. Increased
age and severe
varicose veins both
significantly
associated with
developing DVT. 2
patients developed
symptoms of PE (1
positive for DVT),
but not confirmed
objectively.
Not reported:
Proximal DVT, PE,
PTS, QoL, LoS,
survival.
DRAFT FOR CONSULTATION
Evidence Table 43: Dextran vs aspirin
Bibliographic
reference
Harris et al,
210
1974
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 187
randomised
(results for
168)
Interventio
n1: n = 55
Interventio
n2: n = 62
Control: n
= 51
Patients
characteristics
Type of surgery:
Total hip
replacement.
Duration of surgery
not reported.
Intervention1:
Mean age: 58.4 yrs
(s.d. not reported)
M/F:20/33
Intervention2:
Mean age: 55.5 yrs
(s.d. not reported)
M/F:35/26
Control:
Mean age: 57.7. yrs
M/F:21/29
Pre-existing risk
factors: Obesity (no
significant diffs
between groups).
Intervention
Intervention 1:
Type: adjusted dose
warfarin
Dose: 5mg
pre-op then adjusted
PTT 1.5 x control (or
for 18 secs)
Intervention 2:
Type: Low molecular
weight dextran 10%
w/vs Dose: 500 ml
Duration – all
interventions:
Continued until the
patient was fully
ambulatory and ready
for discharge
Comparison
Type: Aspirin
Dose: 1200 mg
Duration
Continued until
the patient was
fully ambulatory
and ready for
discharge
Additional noncomparative
prophylaxis: All
patients wore
stockings during
and post-surgery,
leg elevation, foot
and ankle
exercises
Additional noncomparative
prophylaxis: All
patients wore
stockings during and
post-surgery, leg
elevation, foot and
ankle exercises
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
Outcome
measures
All groups: DVT Confirmed
until
by:
discharge
Venography,
radioiodine (I,
125) fibrogin
uptake test
Proximal DVT
Confirmed by:
Venography,
radioiodine (I,
125) fibrogin
uptake test
Length of
Hospital Stay
Effect size
Comments
Int1: 10/55
Int2: 14/62
Control: 18/51
p value: No
significant
differences between
groups.
Comments:
Fourth group of
patients received
LDUH. This arm
excluded due to a
change in dose
after 12 patients,
and then
Int1: 3/55
discontinued after
Int2: 8/62
20 patients. 2
Control: 10/51
patients in the
p value: No
dextran group
significant
differences between received a clinical
diagnosis of PE.
groups.
Multiple thrombi
Mean (all groups): were significantly
21 days. (No
more common in
significant difference patients receiving
between groups)
aspirin than either
warfarin or dextran.
Funding: Not
reported
344 of 648
DRAFT FOR CONSULTATION
Evidence Table 44: Unfractionated Heparin (UFH) vs no prophylaxis
Bibliographic
reference
Collins 1988
(74 studies
included)
1,4-
6,14,39,40,48,50,87,92,
98,103,114,125,127,13
4,134,175,179,180,192,
197,198,205,219,265,2
72,282,284288,296,300,300307,317,317,331,333,3
34,338,341,344,373,37
5,376,384,410,426-
Study
Type
Evidenc
e level
Systemat 1+
ic Review
No. of
patients
Patients
characteristics
Type of surgery:
Total:
general, orthopaedic
15598
Interventio and urological.
n: 8112
Control:
7486
Intervention
UFH
Comparison
Nil
Dose: Subcutaneous
and given
perioeratively.
Additional noncomparative
prophylaxis:
GCS: 8 studies
Aspirin: 2 studies
Dextran: 1 study
IPC: 1 study
Additional noncomparative
prophylaxis:
GCS: 8 studies
Aspirin: 2 studies
Dextran: 1 study
IPC: 1 study
Length of
follow up
Outcome
measures
Given for 216 days or
unitl
ambulatory
or
discharged.
DVT confirmed by
radiolabelled
fibrinogen or
scanning
Int: 436/3677
Cont: 922/3389
p value: 0.0000
PE
Int: 74/1840
Cont: 104/1837
p value: 0.0212
Major bleeds
Int: 168/4433
Cont: 110/4177
p value: 0.0027
Proximal DVT
Int: 54/1563
Cont: 114/1563
p value: 0.0000
Effect size
428,439,440,454,465,4
78,486,491,495,502,50
4,516,519,520,524,542,
551,559,560,567
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
345 of 648
Comments
Not reported:
Funding, QoL, LoS
or PTS.
DRAFT FOR CONSULTATION
UFH vs no prophylaxis
Bibliographic
reference
Ballard et al,
28
1973
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 110
Type of surgery:
Elective major
Intervention gynaecological
surgery
: n = 55
Control: n = (& Duration of
surgery)
55
Intervention
Comparison
Type:
Type:
no heparin
5000 units of
Calciparine
(Laboratoire Choay,
Pairs) or sodium
heparin by deep
subcutaneous injection
Intervention: Mean Timing:
age: 53.1±9.9 yrs
started 1 to 2 hours
M/F: not reported
preoperatively and
every 12 hours for 7
days..
Timing:
n/a
Control: Mean age:
50.4±8.7
M/F: not reported
Additional noncomparative
prophylaxis:
routine
postoperative
exercises and
physiotherapy,
with mobilisation
on the second or
third day postoperatively
21/55 had epidural
anaesthesia
Pre-existing risk
factors:
Sever varicose
veins:
Int: 10/55
Cont: 14/55
not significant
No. patients above
interquartile weight
for height:
Int: 20/40
Cont: 27/42
Additional noncomparative
prophylaxis:
routine postoperative
exercises and
physiotherapy, with
mobilisation on the
second or third day
post-operatively
24/55 had epidural
anaesthesia
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
346 of 648
Length of
follow up
7 days
postoperatively
Outcome
measures
Effect size
DVT Confirmed
by:
I-labelled
fibrinogen
Int: 2/55
Contol: 16/55
p value: <0.001
Distal DVT
Confirmed by:
125
I-labelled
fibrinogen
Int: 2/55
Contol: 16/55
p value: <0.001
125
Comments
Not reported:
PE
PTS
bleeding
QoL
Funding:
not reported
DRAFT FOR CONSULTATION
UFH vs no prophylaxis
Bibliographic
reference
Beisaw et al
38
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 128
Interventio
n: n = 65
Control: n
= 63
Type of surgery:
Total hip
replacement
(&
Duration of surgery)
148
randomised
(11
intervention
and 9
control
excluded)
Intervention:
Mean age: 64 (range
43-81) yrs
M/F:26/37
Control:
Mean age: 66.2
M/F:26/39
Pre-existing risk
factors: Obesity,
previous fracture,
varicose veins,
previon DVT (no
significant
differences between
groups).
Intervention
Type: LDUH
5000 IU
Dose:
Comparison
Type: Placebo
Timing: Begun 2hrs
pre-op and repeated
three times daily for at
least 7 days (patients
hospitalised for longer
than 7 days were
treated for up to two
additional days).
Timing: Same
schedule as
intervention group
Additional noncomparative
prophylaxis:
Not reported
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
347 of 648
Length of
follow up
Both
groups:
7th-9th day
post-op
Outcome
measures
Effect size
Comments
DVT Confirmed
by: I125 FUT daily
until patient
completed study.
Venography on
final day (earlier if
FUT positive)
Efficacy analysis:
Int: 16/65
Control: 34/65
p value: 0.0021
Also reported:
Intraoperative
blood loss,
Intention to treat:
(Venograms
available for 136
patients)
Int: 16/69
Control: 34/67
p value: 0.0013
Not reported: N/A
PVT Confirmed
by: as above
Int: 3/63
Control: 12/65
p value: 0.0255
PE
Confirmed
by: Clinical
suspicion
investigated by
“scans of the
lungs”.
Int: 0/63
Control: 2/65
p value: 0.0003
DRAFT FOR CONSULTATION
UFH vs no prophylaxis
Bibliographic
reference
Study
Type
Christensen et RCT
95
al 1989
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 55
Interventio
n: n = 28
Control: n
= 27
Type of surgery:
Total hip
replacement
(&
Duration of surgery)
All patients:
Median age: 70
72 patients (range 348-80) yrs
randomised M/F:21/34
No differences
between the groups
in age or sex
Intervention
Type: LDUH (+DHE)
Dose: 5000 IU (0.5
mg)
Comparison
Type: Placebo
Timing: Not
Timing: Begun one
reported
hour pre-op and
repeated twice daily for
7 days
Additional noncomparative
prophylaxis: All
patients wore thighlength stockings until
full ambulation
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Additional noncomparative
prophylaxis: All
patients wore
thigh-length
stockings until full
ambulation
348 of 648
Length of
follow up
Both
groups:
clinical
exam 3
months
post-op
Outcome
measures
Effect size
Comments
DVT Confirmed
Int: 3/28
by: Tc plasmin
Control: 3/27
test, confirmed by p value: 0.648
ascending
nd
venography on 2
th
and 7 post-op
day.
Comments: No
further
thromboembolic
events were
detected at 3 month
follow up clinical
exam
PE
Confirmed Int: 1/28
by: All patients
Control: 1/27
received V/Q on
p value: 1.000
nd
th
2 and 7 post-op
day
Not reported: PVT,
PTS, QoL, survival,
LoS, funding
Bleeding related
complications
Peri and postoperative blood
loss: not defined
Mean blood loss:
Int: 865ml
Control: 902 ml
p value: 0.79 Not
significant
DRAFT FOR CONSULTATION
UFH vs no prophylaxis
Bibliographic
reference
ClarkePearson et al,
100
1990
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 324
Type of surgery:
major abdominal or
pelvic surgical
procedure for
gynaecological
malignancy (radical
vulvectomy or pelvic
exenteration).
Patients stratified by
risk factor.
Type:
UFH (Calciparine)
5000 units in 1mL
volume every 8 hours
Intervention:
Median (range) age:
61.5 (43-85) yrs
M/F: not reported
Int 1: n =
104
Cont: n =
103
(3rd arm n
= 97 not
included)
Intervention
Comparison
Length of
follow up
7
postoperati
ve days for
intervention
, followed
clinically for
30
postoperati
vedays
Outcome
measures
Effect size
Comments
DVT Confirmed
by: FUT.
Int: 9/104
Control: 19/103
p value: 0.04
Bilateral DVT
Confirmed by:
FUT.
Int: 2/104
Control: 4/103
p value: 0.4451
Comments:
20 patients dropped
out after
randomisation
mainly due to
operation
cancellation. None
developed
evidence of DVT or
PE
Timing:
Started 2 hours
preoperatively then
every 8 hours for 7
days postoperatively.
Symptomatic PE
Confirmed by:
pulmonary
arteriography
Int: 2/104
Control: 0/103
p value: 0.4976
No additional
prophylaxis used.
Control: Median
(range) age: 60 (4084) yrs
M/F: not reported
Type (3rd arm): UFH
(Calciparine) 5000
units in 1mL volume
Fatal PE
Int: 0/104
Control: 0/103
p value: N/A
Pre-existing risk
factors:
Past history of DVT
or PE
Int: 5
Control: 3
3rd arm: 3
Timing:
First dose immediately
after randomisation
then then every 8
hours up to surgery.
Because of differing
lengths of preoperative
stay patients in this
group received varying
numbers of doses:
14 received 2 doses
82 received 3-6 doses
2 received 8 or 9
doses
Postoperative
Int: 6/104
thrombocytopeni Control: 12/103
a
p value: 0.1472
Excluded: past
history of bleeding
diathesis;
thromboembolism
within previous 3
months; warfarin or
heparin treatment
within previous 6
weeks
Type:
no treatment
Additional noncomparative
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
349 of 648
Median (range)
estimated blood
loss mL
Int: 500 (50-4520)
mL
Control: 500 (106000)
p value: not
significant
Intraoperative
and
postoperative
transfusions
Int: 0 (0-6) U
Control: 0 (0-24) U
p value: not
significant
Other outcomes
reported:
retroperitoneal
suction output; no.
with postoperative
hematocrit <30%;
wound separation;
lymphocyst.
Not reported:
PTS, QoL, survival.
length of hospital
stay, funding.
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
350 of 648
Length of
follow up
Outcome
measures
Effect size
Comments
DRAFT FOR CONSULTATION
Evidence Table 45: UFH - dose
Bibliographic
reference
Cade et al
85
1983
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 100
Intervention
: n = 51
Control: n =
49
Patients
characteristics
Intervention
Type: LDUH
Type of surgery:
Major thoracic (incl. 7500 IU
lobectomy,
pneumonectomy,
oesophagogastrecto
my, thoracotomy)
(& Duration of
surgery)
Dose:
Comparison
Type: LDUH
Dose: 5000 IU
Intervention: Mean Timing: Begun 1-2 hrs
age: 60 (range 46pre-op then repeated
77) yrs M/F:42/9
twice daily until patient
fully ambulated
Timing: Begun 12 hrs pre-op then
repeated twice
daily until patient
fully ambulated
Control: Mean age: Additional non61 (range 44-86) yrs comparative
M/F:38/11
prophylaxis: Electrical
calf muscle stimulation
during surgery
Additional noncomparative
prophylaxis:
Electrical calf
muscle stimulation
during surgery
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
351 of 648
Length of
follow up
Outcome
measures
10 days or
until the
patient was
fully
amublant
(at least 5
days).
DVT Confirmed
by: FUT daily until
patient fully
th
ambulant or 10
post-op day
Int: 11/51
Control: 11/49
p value: > 0.2
Comments: DVT
significantly more
common in male
than female
patients.
Bleeding related
complications
Postoperative
bleeding:
measured blood
loss from thoracic
drain tubes and
post-operative
transfusion needs
Actual values not
reported. No
excessive bleeding
was reported and
there was no
clinically detectable
difference in
bleeding between
the two groups
Not reported:
PVT, PE, PTS,
QoL, Survival, LoS.
Effect size
Comments
DRAFT FOR CONSULTATION
Evidence Table 46: Low Molecular Weight Heparin (LMWH) vs no prophylaxis
Bibliographic
reference
Iorio et al,
256
2000
3 RCT studies
19,360,388
Study
Type
Evidenc
e level
Systemat 1+
ic Review
No. of
patients
Patients
characteristics
Total: 922 Type of surgery:
Interventio Neurosurgery
n:461
Control:46
1
Intervention
LWMH
Comparison
Placebo
Doses:
Enoxaparin: 40mg/day
(1 study) and
20mg/day (1 study)
Nadroparin 7500 antiXa units/d (1 study)
Proximal DVT
Background
prophylaxis:
GCS 2 studies
Int: 63/360
Cont: 104/367
[OR: 0.54 (95% CI
0.38-0.77);
p value: <0.001
Int: 19/304
Cont: 39/312
Int: 10/461
Cont: 6/461
[OR=1.68 (95% CI
0.62-4.52);
p value: 0.30
Fatal PE
352 of 648
Effect size
[OR=0.48 (95% CI
0.28-0.83);
p value: 0.008
Major bleeding
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Outcome
measures
Follow up
DVT confirmed by
30 days for venography
one study
and 56
days for the
second
study.
The third
study did
not report
follow up
period.
Timing: Started within
24 hours
postoperatively and
given daily for ≥7 days
(in one study) to 10
days (in two studies).
Background
prophylaxis:
GCS 2 studies
Length of
follow up
Int: 1/371
Cont: 3/374
p value: 0.6240
Comments
Not reported: QoL,
LoS, PTS and
funding.
DRAFT FOR CONSULTATION
LMWH vs no prophylaxis
Bibliographic
reference
Study
Type
Evidenc
e level
Mismetti et al,
364
2001
Systemat 1+
ic review
8 studies
included
(8
studies)
27,49,230,318,342,393,
403,404,515
No. of
patients
Patients
characteristics
Total: 5520 Type of surgery:
General (7 studies)
Urology (1 study)
Not all studies
reported on all
outcomes.
Intervention
Type: LMWH
Comparison
Type: nil or
placebo
Timing: preoperative
7 studies, post
operative 1 study
Duration: 4-9 days
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
353 of 648
Length of
follow up
7 days-9
months
Outcome
measures
Effect size
DVT (Clinical,
confirmed by US
or veno/FUT)
Int: 9/258
Cont: 37/255
p value: 0.000
PE
(intervention:
both fatalities)
Int: 2/2526
Cont: 13/2558
p value: 0.0073
Major Bleeding
Int: 75/2710
Cont: 337/2746
p value: 0.0000
Proximal DVT
Int: 0/50
Cont: 2/50
p value: 0.4949
Comments
Also reported,
wound haemotoma,
death, but data not
given for patient
numbers by
control/intervention
group.
DRAFT FOR CONSULTATION
LMWH vs no prophylaxis
Bibliographic
reference
Zuffrey et al,
568
2003
13 studies
263,276,312-
314,319,324,444,476,5
01,511,535,561
Study
Type
Evidenc
e level
Systemat 1+
ic Review
No. of
patients
Patients
characteristics
Total: 1925 Type of surgery:
Hip fracture: 3
Int:928
studies
Cont:940
Knee surgery: 2
studies
Note: 2
studies did Hip replacement 8
studies
not give
total
distribution
of
randomised
patients
and only
gave
number for
those that
had
detection
test.
Intervention
LMWH: (Enoxaparin,
certoparin, tinzaparin,
dalteparin, nadroparin,
ardeparin)
Comparison
Placebo (11
studies) or No
treatment (2
studies)
Doses:
Ranged from 3000
anti-Xa IU to over 6000 background:
GCS in 4 studies.
anti-Xa IU.
electrical
stimulation 2
Timing:
studies
Treatment started
preoperatively in 9
studies and
postoperatively in 4
studies. The treatment
varied from 3 to 14
days
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
354 of 648
Length of
follow up
Outcome
measures
Studies
ranged rom
6 to 14
days followup.
DVT confirmed by
fibrinogen or
plasminogen
uptake test,
duplex US or
venography.
Int: 199/823
Cont: 416/835
RR=0.51, 95% CI
0.45-0.59;
p value: <0.001
Proximal DVT
Int: 66/779
Cont: 163/760
RR=0.35, 95% CI
0.21 – 0.57;
p value: <0.001
(reported from 11
studies)
Major bleeds
(defined as major
haemorrhage)
Int: 7/550
Cont: 10/555
RR=0.80, 95% CI
0.36-1.79;
p value: =0.58
(reported from 7
studies)
PE
Int: 4/344
Cont: 8/379
(reported from 5
studies)
p value: 0.3905
Effect size
Comments
Not reported: QoL,
LoS, PTS and
funding.
Note: RR and CI
reported by SR
authors.
DRAFT FOR CONSULTATION
LMWH vs no prophylaxis
Bibliographic
reference
Bergqvist et
43
al, 1996
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Intervention
Total: 262
Intervention
n: 131
Control n:
131
Type of surgery:
Patients scheduled
for Total hip
replacement
surgery. Surgery
was performed
expeditiously with a
mean duration of 1.9
hours (range 1.0 to
5.0).
Type, dose and
timing:
40 mg of Enoxaparin
injected sub
cutaneously into
abdomen once daily.
The first active dose
was given 12±2 hrs
preoperatively until day
21
Intervention: Mean
age: 70 (range: 44 87 years)
M/F:56/75
Additional noncomparative
prophylaxis:
Not reported
Comparison
Type, dose and
timing: Placebo
or Single dose of
0.4 ml saline.
Control: Mean age:
70 (Range: 44 – 87
years)
M/F:57/74
Pre-existing risk
factors:
Previous VTE: Int: n
= 8 Control: n = 12
Varicose veins: Int:
n = 27 Control: n =
31
Leg ulcer: Int: n = 2
Control: n = 3
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
355 of 648
Length of
follow up
3 months
Outcome
measures
Effect size
DVT confirmed by
bilateral
ascending
phlebography
Int: 21/117
Control: 43/116
p value: 0.0012
PE Confirmed by
ventilation –
perfusion lung
scan or a
pulmonary
angiography.
Int: 0/117
Control: 2/116
p value: 0.2468
Comments
DRAFT FOR CONSULTATION
LMWH vs no prophylaxis
Bibliographic
reference
Michot et al,
362
2002
Study
Type
Evidence
level
RCT
1+
No. of
patients
Total: 130
Intervention
n: 66
Control n: 64
Patients
characteristics
Type of surgery:
Patients scheduled
for diagnostic or
therapeutic
arthroscopic knee
surgery. Surgery
was performed
expeditiously with a
mean duration of
42.3 mins.
Intervention: Mean
age: 42 (SD, 14.7
years) M/F:40/60
Control: Mean age:
46.5 (SD, 13.2
years)
M/F:46/54
Intervention
Comparison
Length of
follow up
30 days
Type, dose and timing: Type, dose
and timing: No
First dose of
prophylaxis
subcutaxneous LMWH
(2500 IU anti-FXa
Dalteparin) 60-120 mins
before start of procedure.
Second weight adapted
dose (2500 IU if weight
<70 kg, 5000 IU if >70 kg)
was given 6 hrs after
surgery for upto 30 days
post op.
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
356 of 648
Outcome measures
DVT confirmed by
Clinical examination,
routine platelet count
and bilateral US.
Effect size
Thromboembolic
events
Int: 1*/66
Control: 10/64
p value: 0.004
If no compression US
was available then a
venography was
performed.
PE Confirmed by
ventilation – perfusion
lung scan or a
pulmonary
angiography.
Int: 1*/66
Control: 0/64
Bleeding
complications:
Int: 8/66
Control: 4/64
p value: 0.365
Major bleeding
Int: 0/66
Control: 0/64
p value: 0.0559
Same patient with
DVT &
symptomatic PE
Comments
Pre-existing risk
factors:
Family history of
VTE/PE: int: 5; Cont:
6.
Estrogen
therapy/oral
contraceptives: int:
4; Cont: 0.
Oral contraceptives
smoking : int: 3;
Cont: 1.
Varicose veins: int:
8; Cont: 9.
Preoperative
immobility/reduced
weight bearing: int:
4; Cont: 4.
DRAFT FOR CONSULTATION
LMWH vs no prophylaxis
Bibliographic
reference
Wirth et al,
555
2001
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 239
Interventio
n n: 117
Control n:
122
Type of surgery:
Patients scheduled
for arthroscopic
knee surgery.
Surgery was
performed
expeditiously with a
mean duration of 34
mins (± 38 mins).
Intervention
Comparison
Type, dose and
Type, dose and
timing: One dose daily timing: No
prophylaxis
of subcutaneous
LMWH (1750 IU antiXa Reviparin) for 7-10
days after surgery?
Additional noncomparative
prophylaxis:
Intervention: Mean Not reported
age: 37.6 (SD, ±13.0
years) M/F:81/36
Control: Mean age:
38.5 (SD, ±11.6
years)
M/F:98/24
Pre-existing risk
factors:
No risk factors: Int:
n = 73 Control: n =
77
1 risk factor: Int: n =
42 Control: n = 39
2 risk factors: Int: n
= 2 Control: n = 6
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
357 of 648
Length of
follow up
7 - 10 days
Outcome
measures
Effect size
DVT confirmed by Int: 1/117
compression color Control: 5/122
- coded US.
p value: 0.2134
PE Confirmed by
?
Int: 0/117
Control: 0/122
p value: N/A
Major bleeding
Int: 0/117
Control: 0/122
p value: N/A
Minor bleeding
Int: 3/117
Control: 1/122
p value: 0.3616
Hospital stay:
Int: 1.5/117; SD
±1.9
Control: 1.3/122;
SD ±2.8
p value: 0.7326
Comments
DRAFT FOR CONSULTATION
Evidence Table 47: LMWH Timing: Pre-op versus post-op Initiation
Bibliographic
reference
Palareti et al
401
1996
Study
Type
RCT
Evidence
level
1+
No. of
patients
Total: 180
randomised
(outcome for
131)
Intervention:
n = 91 (65
assessed for
VTE)
Control: n =
89 (66
assessed for
VTE)
Patients
characteristics
Intervention
Comparison
Timing: Placebo
12hrs pre-op, and
then LMWH 7500
units begun eve
post-op and
repeated daily
rd
until 3 day postop. Then 10000
units daily until
discharge or for
14 days.
Proximal DVT
Confirmed by:
Bilateral
ascending
venography on
th
th
10 -15 post-op
day, or earlier if
symptomatic
Int: 7/65
Control: 4/66
p value: Not
significant
PE
Confirmed
by: Not routinely
assessed. Clinical
suspicion
investigated with
V/Q scan
Int: 0/90
Control: 0/89
p value: N/A
Additional noncomparative
prophylaxis:
Early mobilisation,
graduated
compression
stockings,
physical exercise
Bleeding related
complications
Safety analysis
(179 patients. 1
patient excluded wrong intervention)
Major
haemorrhage
Int: 2/90
Control: 3/89
p value: Not
significant
Type: LMWH
(nadropain)
begun postoperatively
Dose: 7500 IU,
10000 IU
Duration of
surgery:
Int: 84.6±29.4 min
Cont: 80.0±28.4 min
Timing: 7500 units
begun 12hrs pre-op
and repeated daily
rd
until 3 day post-op.
Then 10000 units
daily until for 14 days
or until discharge.
Pre-existing risk
factors: age,
obesity, varicose
veins, previous VTE
(no significant
Additional noncomparative
prophylaxis: Early
mobilisation,
graduated
compression
stockings, physical
exercise
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Effect size
Int: 27/65
Control: 24/66
p value: Not
significant
Type: LMWH
(nadropain) begun
pre-operatively
Dose: 7500 IU,
10000 IU
Control: Mean age:
61.3±7.6 yrs
M/F:29/60
Outcome
measures
DVT Confirmed
by: Bilateral
ascending
venography on
10th-15th post-op
day, or earlier if
symptomatic
Type of surgery:
Elective hip
replacement
Intervention: Mean
age: 62.3±6.8 yrs
M/F:26/65
Length of
follow up
358 of 648
Both
groups: 46 weeks
post-op
Comments
Comments: Multicentre study
involving 7
orthopaedic
departments.
Across the whole
study group, age
was a significant
risk factor for
developing DVT.
* intracranial, ocular
(with reduction of
viscus), articular,
retroperitoneal,
and/or associated
with reduction of
haemoglobin ≥
2g/dl or a need to
transfuse ≥ 2 U of
blood
Not reported: PTS,
QoL, LoS, survival,
funding
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidence
level
No. of
patients
Patients
characteristics
Intervention
Comparison
differences between
groups).
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
Outcome
measures
Minor
haemorrhage:
clinically evident
but without *
359 of 648
Effect size
Int: 14/90
Control: 11/89
p value: Not
significant
Comments
DRAFT FOR CONSULTATION
Evidence Table 48: LMWH studies comparing dose
Bibliographic
reference
Adolf et al,
7
1999
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 341
randomised
Interventio
n: n = 169
Control: n
= 172
(81
exclusions,
34
intervention
, 47
control).
Type of surgery:
Total hip
replacement
(&
Duration of surgery)
Type: Increased dose
LWMH (Certoparin)
Dose: 5000 IU
Type: standard
dose LMWH
(Certoparin)
Dose: 3000 IU
Randomised
patients
Intervention: Mean
age: 67±11.7 yrs
M/F:70/99
Timing: Begun at least
2 hours pre-op, then
repeated daily until
th
th
12 -14 day post-op
Randomised
patients
Control: Mean age:
69±9.5 M/F:64/108
Additional noncomparative
prophylaxis:
none reported
Intervention
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Length of
follow up
Outcome
measures
Effect size
Comments
DVT Confirmed
by: Bilateral
ascending
venography on
12-14th post-op
day (earlier if
symptomatic)
Intention to treat
analysis:
Int: 16/169
Control: 17/172
p value: 0.9
Comments: Multicentre trial.
Timing: Begun at
least 2 hours preop, then repeated
th
th
daily until 12 -14
day post-op
Proximal DVT
Confirmed by:
venography
Intention to treat:
Int: 4/169
Control: 2/172
p value: 0.4456
Not reported: PTS,
QoL, LoS, funding
Additional noncomparative
prophylaxis:
none reported
Symptomatic PE
Confirmed by:
Suposed to be by
V/Q scan but
appears not to be
case.
Int: 2/169
Control: 2/172
p value: 1.0000
360 of 648
Both
groups:
12-14 days
post-op
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Length of
follow up
Outcome
measures
Bleeding related
complications:
- Transfusion
volumes
- Cell saver
volumes
- Drain loss
- Haematoma
formation
Pre-existing risk
factors:
Smoking 44/341
Previous DVT
29/341
Previous PE 5/341
Varicose veins
133/341
(no significant
difference between
groups).
Effect size
Transfusion
volumes:
Int: Mean 1004±478
ml Control:
950±517 ml
p
value: Not
significant
Cell saver vol:
Int: 475±186 ml
Control: 770±136
p value: <0.001
(Significant)
Drain loss:
Int: 752±351
Control: 790±374
p value: Not
significant
Haematoma
formation:
Int: 28/169
Control: 26/172 p
value: Not
significant
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
361 of 648
Comments
Funding:
DRAFT FOR CONSULTATION
LMWH studies comparing dose
Bibliographic
reference
Bergqvist et
45
al, 1995
Study
Type
Multicent
re RCT
Evidenc
e level
1+
No. of
patients
Total:
2070
Int: 1036
Cont: 1034
Patients
characteristics
Intervention
Comparison
Type of surgery:
Elective general
abdominal surgery.
Type:
LMWH (dalteparin)
5000 units daily
Type:
LMWH
(dalteparin) 2500
units daily
Intervention:
Median (range) age:
70 (40-90) yrs
M/F: 513/523
Median (range)
duration of surgery:
125 (15-525)
minutes
Timing:
Started at 22 hours the
day before surgery for
7 days postoperatively.
Timing:
Started at 22
hours the day
before surgery for
7 days
postoperatively.
Control:
Median age: 69 (4095) yrs
M/F: 472/562
Median (range)
duration of surgery:
129 (19-470)
minutes
Additional noncomparative
prophylaxis:
none reported
Additional noncomparative
prophylaxis:
none reported
7
postoperati
ve days for
intervention
, followed
up at 30
postoperati
vedays
Outcome
measures
DVT Confirmed
by: FUT.
Effect size
Int: 65/981
Control: 124/976
p value: <0.001
Total no bleeding Int: 49/1036
episodes
Control: 28/1034
p value: 0.02
Major bleeding
episodes
Int: 13/1036
Control: 3/1034
p value: 0.0208
Minor bleeding
episodes
Int: 36/1036
Control: 25/1034
p value: 0.1543
Median (range)
intraoperative
blood loss mL
Mortality
(confirmed by
autopsy)
Pre-existing risk
factors:
Past history of DVT
or PE
Int: 62/1036
Control: 60/1034
Comments
Comments:
20 patients dropped
out after
randomisation
mainly due to
operation
cancellation. None
developed
evidence of DVT or
PE
No additional
prophylaxis used.
Other outcomes
reported:
PE (not all
confirmed by
accepted diagnostic
Int: 300 (0-7800) mL test), 1 fatal PE in
Control: 300 (0each arm confirmed
30,000)
by autopsy but not
p value: not
all deaths received
reported
imaging or autopsy.
Int: 32(15)/1036
Control:
35(12)/1034
p value:
Not reported:
Proximal and distal
DVT, PTS, QoL,
length of hospital
stay.
Funding: not
reported
Excluded: past
history of bleeding
diathesis; oral
anticoagulant or
dextran treatment
within previous 14
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
362 of 648
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
days
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
363 of 648
Length of
follow up
Outcome
measures
Effect size
Comments
DRAFT FOR CONSULTATION
LMWH studies comparing dose
Bibliographic
reference
Colwell et al,
108
1994
Study
Type
Multicent
re RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 610
Type of surgery:
Hip replacement
Multicentre surgery, including
primary and revision
study
involving 32 procedures, in
institutions patients 40 years or
older
Int A: 195
In B: 203
Int C: 209
Intervention A:
Mean age:
65.6±10.97 yrs
M/F:98/97
Intervention
Int A:
Enoxaparin 30mg
every 12 hours
Timing:
Administered within 24
hours after surgery
and continued for a
maximum of 7 days.
Intervention B:
Mean age:
65.0±11.31 yrs
M/F:99/104
Intervention C:
Mean age:
65.6±10.65 yrs
M/F:101/108
Pre-existing risk
factors:
Excluded patients
include: a history of
DVT, PE or both and
heparin associated
thrombocytopenia.
Additional noncomparative
prophylaxis:
No. patients receiving
epidural/spinal
anaesthesia:
Int A: 64/195
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Length of
follow up
Outcome
measures
Effect size
DVT Confirmed
by: bilateral
contrast
venography
Int A: 8 (n = 136)
Int B: 28 (n = 136)
Int C: 21 (n = 142)
p value not
reported
Int C:
5000 units UFH
every 8 hours
Proximal DVT
Confirmed by:
bilateral contrast
venography
Int A: 4 (n = 136)
Int B: 8 (n = 136)
Int C: 10 (n = 142)
p value not
reported
Timing:
Administered
within 24 hours
after surgery and
continued for a
maximum of 7
days.
Distal DVT
Confirmed by:
bilateral contrast
venography
Int A: 4 (n = 136)
Int B: 20 (n = 136)
Int C: 11 (n = 142)
p value not
reported
PEs
(symptomatic)
(not reported how
confirmed)
Int A: 0 (n = 195)
Int B: 1 (n = 203)
Int C: 3 (n = 209)
p value: not
reported
Major bleeding
episodes
Int A: 8 (n = 195)
Int B: 3 (n = 203)
Int C: 13 (n = 209)
p value: not
reported
Moderate
thrombocytopeni
a episodes
9
(20x10 /L to
9
100x10 /L. In no
case was the
9
count <50x10 /L).
Int A:7 (n = 195)
Int B: 3 (n = 203)
Int C: 5 (n = 209)
p value: not
reported
Mortality during
study
not due to sudden
Int A: 1 (n = 136)
Int B: 0 (n = 136)
Int C: 2 (n = 142)
Int B:
Enoxaparin 40mg
once daily
Additional noncomparative
prophylaxis:
No. patients
receiving
epidural/spinal
anaesthesia:
Int B: 72/203
Int C: 72/209
364 of 648
Study
period:
7 days
Comments
Comments:
Only 67.9% of
patients evaluated
for DVT.
Multicentre study,
not all centres used
a valid diagnostic
technique (same
numbers in each
group). An intention
to treat analysis
was followed.
Results are
available for
patients diagnosed
by valid test alone
as well as all
patients.
Other outcomes
reported:
Total proximal and
distal DVTs (i.e.
confirmed by
venography,
supportive noninvasive vascular
examinations or
other clinical
evidence of
treatment failure.)
hemoglobin levels,
minor bleeding
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
365 of 648
Length of
follow up
Outcome
measures
Effect size
Comments
death by PE
p value not
reported
Adverse events
(no. of patients,
none completed
the study)
Int A: 7 (n = 136)
Int B: 5 (n = 136)
Int C: 12 (n = 142)
p value not
reported
Not reported:
PEs in hospital
PTS, QoL,
No. of patients
rehospitalised
(due to
symptomatic DVT
or PE).
Int A: 3 (n = 136)
Int B: 1 (n = 136)
Int C: 4 (n = 142)
p value not
reported
Funding:
Rhone Poulenc
Pharmaceuticals
DRAFT FOR CONSULTATION
LMWH studies comparing dose
Bibliographic
reference
Hauch et al,
214
1988
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 35
Int: n =
19
Control: n =
16
Type of surgery:
Major abdominal
(& Duration of
surgery)
42 patients
randomised
Int: n = 20
Control n =
22
Intervention:
Median age 72
(range 40-88) yrs
M/F:8/11
Control: Median
age 68 (range 4185) M/F:5/11
Pre-existing risk
factors:
No. of patients with
predisposing risk
factors (malignant
disease, varicose
veins, previous
thromboembolism,
myocardial
infarction):
Int: 13
Cont: 7
Intervention
Type: LMWH
Dose: 3500 IU
Comparison
Type: LMWH
Dose: 2500 IU
Timing:
started 2 hours
preoperatively and
administered once
daily until
postoperative day 7 or
discharge
Timing:
started 2 hours
preoperatively and
administered once
daily until
postoperative day
7 or discharge
Additional noncomparative
prophylaxis:
none reported
Additional noncomparative
prophylaxis:
none reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
366 of 648
Length of
follow up
1 month
Outcome
measures
Effect size
DVT Confirmed
Int: 0/19
125
st
by: I FUT on 1 , Control: 2/16
rd
th
th
p value: 0.20
3 , 5 and 7
post-op day
(positive result
confirmed by
venography)
Symptomatic PE
(confirmation not
reported)
Int: 0/19
Control: 0/16
p value: N/A
Fatal PE
Autopsy:
Int: 0/19
Control: 0/16
p value: N/A
Major bleeds
Int: 1/19
Control: 0/16
p value: 0.54
Comments
Not reported:
QoL, survival, LoS,
PTS, funding
Also reported:
3rd arm
investigating a dose
of 50 IU per kg of
body weight.
DRAFT FOR CONSULTATION
LMWH studies comparing dose
Bibliographic
reference
Spiro et al,
479
1994
Study
Type
Multicent
re RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Intervention
Total: 572
Int A:
Type of surgery:
Enoxaparin 30mg
Hip replacement
every 12 hours
Multicentre surgery, including
primary and revision
study
involving 32 procedures, in
institutions patients 31 years or
older
Int A: 210
Intervention: Mean
In B: 201
age: 65.2±10.6 yrs
Int C: 161
M/F:124/84
(see
comments)
Control: Mean age:
64.8±10.3 yrs
M/F:127/72
rd
3 discontinued
arm: Mean age:
63.9±10.5 yrs
M/F:107/54
Timing: Administered
within 24 hours after
surgery and continued
for as long as 7 days.
Additional noncomparative
prophylaxis:
Not reported
Comparison
Int B:
Enoxaparin 40mg
once daily
Int C:
rd
3 arm
Enoxaparin 10mg
once daily
Timing:
administered
within 24 hours
after surgery and
continued for as
long as 7 days.
Pre-existing risk
factors:
Excluded patients
include: a history of
DVT, PE or both and
heparin associated
thrombocytopenia.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
367 of 648
Length of
follow up
Study
period:
7 days, or
earlier if
indicated,
or on day of
discharge.
Follow up
mentioned
but no
period
given.
Outcome
measures
Effect size
DVT Confirmed
by: bilateral
contrast
venography
Int A: 16/143
Int B: 21/149
Int C: 36/116
p value: A to B
>0.2; C to B =0.005;
C to A <0.001
Proximal DVT
Confirmed by:
bilateral contrast
venography
Int A: 8/143
Int B: 9/149
Int C: 16/116
p value: not
reported
Distal DVT
Confirmed by:
bilateral contrast
venography
Int A: 8/143
Int B: 12/149
Int C: 20/116
p value: not
reported
PE
Confirmed by
clinical evidence
in patients
subsequent to
confirmation of
DVT
Int A: 0/143
Int B: 1/149
Int C: 1/116
p value: not
reported
Major bleeding
episodes
Int A: 11/208
Int B: 7/199
Int C: 3/161
p value: not
reported
Mild
thrombocytopeni
a episodes
(>100x109/L and <
lower limit of
normal)
Int A: 28/208)
Int B: 23/199)
Int C: 17/161)
p value: A to B not
given ; A to C >0.2;
B to C >0.2
Comments
Comments:
Int C was stopped
because of the high
incidence of
treatment failure
Only 71.3% of
patients evaluated
for DVT.
Multicentre study,
not all centres used
a valid diagnostic
technique (same
numbers in each
group). An intention
to treat analysis
was followed.
Results are
available for
patients diagnosed
by valid test alone
as well as all
patients.
Other outcomes
reported:
Total proximal and
distal DVTs (i.e.
confirmed by
venography,
supportive noninvasive vascular
examinations or
other clinical
evidence of
treatment failure.)
thrombocytosis,
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
368 of 648
Length of
follow up
Outcome
measures
Effect size
Moderate
thrombocytopeni
a episodes
9
(20x10 /L to
9
100x10 /L. In no
case was the
9
count <50x10 /L).
Int A: 1/208
Int B: 2/199
Int C: 1/161
p value: A to B not
given; A to C >0.2; B
to C >0.2
Mortality
Int A: 0/208
Int B: 2/199
Int C: 0/161
p value: not
reported
Adverse events
(no. of patients)
Int A: 10/208
Int B: 16/199
Int C: 13/161
p value: not
reported
No. of patients
rehospitalised
Int A: 2/208
Int B: 2/199
Int C: 2/161
p value: not
reported
Comments
hemoglobin levels,
alanine
aminiotransferase,
minor bleeding
Not reported:
PTS, QoL
Funding:
Rhone Poulenc
Pharmaceuticals
DRAFT FOR CONSULTATION
Evidence Table 49: Heparin – extended duration
Bibliographic
reference
Hull 2001
6 RCTs
248
43,111,118,249,311,40
8
Study
Type
Evidenc
e level
Systemat 1+
ic Review
No. of
patients
Patients
characteristics
Total: 1953 Type of surgery:
Orthopaedic
Int: 1091
Cont: 862
Intervention
Extended posthospital LMWH
Comparison
Out of hospital
placebo
Five studies had
LMWH
prophylaxis in
Timing: preoperatively hospital followed
by out of hospital
in four studies and
postoperatively in one placebo. The
remaining study
study. The remaining
study included sparate had a comparator
group that
randomly assigned
received in
groups for
hospital warfarin
preoperative and
followed by out of
postoperative initaion
hospital placebo.
of therapy.
Enoxaparin (3 studies)
Dalteparin (3 studies)
Additional noncomparative
prophylaxis:
GCS – some patients
used in four studies.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Additional noncomparative
prophylaxis:
GCS – some
patients used in
four studies
369 of 648
Length of
follow up
Outcome
measures
In hospital
prophylaxis
ranged
from 6-14
days.
Extneded
out of
hospital
duration
ranged
from 18-29
days.
DVT confirmed by
venography
Int: 105/1006
Cont: 187/810
p value: 0.000
Not reported: QoL,
funding, PTS or
LoS.
PE
Int: 0/899
Cont: 8/884
p value: 0.8139
Proximal DVT
Int: 40/1042
Cont: 92/837
p value: 0.0000
Notes:
Review used hip
replacement data
only for Hull 2000a
trial –the knee
replacement data
has been included.
Effect size
Thrombocytopen Int: 5/1091
ia
[0.46%(CI, 0.15% to
1.07%)]
Cont: 3/862 [0.34%
(CI, 0.07% - 1.01%)]
p value: 1.000
Comments
DRAFT FOR CONSULTATION
Heparin – extended duration
Bibliographic
reference
Bergqvist et
42
al, 2002
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Type of surgery:
Abdominal (curative
surgery for
abdominal/pelvic
Interventio cancer)
n: n = 165
Control: n Patients excluded
from randomisation
= 167
if had objectively
confirmed VTE or
major bleeding.
501
randomised
Duration of
Int: 253
surgery:
Control:
Int: Median: 3hr
248
3min (range 23 min
– 9hr 35min).
Outcome
Cont: Median: 3hr 5
not
obtained/no min (range 45 min –
11hr).
t
interpretabl
e for 88 int. Age and gender:
Intervention:
and 81
Median age: 66,
cont.
range 40-90
patients
M/F: 96/69
Control: Median
age: 65, range 30-87
M/F: 104/63
Total:
Results for
332
Intervention
Comparison
Type: Extended (4 wk) Type: LMWH
LMWH (Enoxaparin)
(1wk)
Dose: 40 mg
(Enoxaparin) then
placebo Dose:
40mg
Timing: begun 10-14
hrs pre-op then once
daily for 25-31 days
Additional noncomparative
prophylaxis:
Not reported
Timing: begun
10-14 hrs pre-op
then once daily for
6-10 days.
Placebo for further
19-21 days.
Both
groups: 3
months ±
10 days
Outcome
measures
Effect size
Int: 8/165
DVT Confirmed
Control: 20/167
by: bilateral
venography within p value: 0.02
3 days of final
injection (days 2531 post-op).
Int: 1/165
Proximal DVT
Control: 3/167
Confirmed by:
p value: 0.6228
bilateral
venography within
3 days of final
injection (days 2531 post-op).
Symptomatic PE Int: 0/165
Confirmed by: V/Q Control: 1/167
scan or angiogram p value: 1.000
Patient with PE also
had distal DVT
Fatal PE
Confirmed by:
autopsy
Int: 0/165
Control: 1/167
p value: 1.000
Fatal PE occurred
during 3 mo. FU
period
Pre-existing risk
factors: All patients
had malignant
cancer. Patients with
history of VTE within
previous 3 mo.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
370 of 648
Major
haemorrhage (at
3 mo FU)*
Int: 3/253
Control: 1/248
p value: 0.62
Minor
haemorrhage (at
3 mo FU)*
Int: 12/253
Control: 9/248
p value: 0.66
Total
haemorrhage (at
3 mo FU)*
Int: 11/253
Control: 18/248
p value: 0.20
Comments
Comments:
Patients
randomised after
initial treatment with
LMWH for 6-10
days. Multi-centre
trial at 37 centres
across 8 European
countries.
Randomisation
stratified by country
where institution
located. Between
site differences not
considered. At 3
mo. FU a further 4
DVTs (1 int. 3
cont.) were
clinically suspected.
Results also
reported for
haemorrhage
during double-blind
and FU periods
separately. No
significant
difference between
groups for any
outcome.
* denominator is
total no of patients
randomised
Not reported: QoL,
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
excluded.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
Outcome
measures
Survival
371 of 648
Effect size
Int: 250/253
Control: 249/248
p value: Not
reported
Comments
LoS
Funding:
Sponsored by
Aventis
pharmaceuticals.
Two company
representatives
were involved in
statistical analysis
and writing of
manuscript.
DRAFT FOR CONSULTATION
Heparin – extended duration
Bibliographic
reference
Manganelli et
340
al, 1998
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 79
randomised
Interventio
n: n = 33
Control: n
= 28
18
withdrawals
(8
intervention
, 10
control).
Patients
characteristics
Intervention
Comparison
Type:unfractionat
Type: Extended
duration unfractionated ed heparin
heparin
Dose: 5000 IU
Dose: 5000 IU
Timing: 5000 IU
Timing: 5000 IU from from 1 day pre-op,
every 8hrs until
Intervention: Mean 1 day pre-op, every
discharge.
8hrs for 30 days
age: 65±8.2 yrs
M/F:10/23
Additional noncomparative
prophylaxis:
Not reported
Type of surgery:
Elective total hip
replacement
Length of
follow up
Both
groups: 45
days postop
Outcome
measures
DVT Confirmed
by: unilateral
ascending
venography on
th
45 day post-op
(earlier if
symptomatic)
Int: 4/33
Control: 6/28
p value: 0.48
Proximal DVT
Confirmed by:
unilateral
ascending
venography on
th
45 day post-op
(earlier if
symptomatic)
Int: 1/33
Control: 5/28
p value: 0.08
Pre-existing risk
factors: Obesity (no
significant
differences between
groups)
Length of
Hospital Stay
372 of 648
Comments
Comments:
Patients
randomised at
discharge. 2
patients had
objectively
confirmed PE, but
the paper does not
report the study
group these
patients were in.
Not reported: PE,
PTS, QoL, Survival,
funding
Int: 0/33
Major
Control: 0/33
haemorrhage
clinically overt and p value: N/A
associated with a
decrease in
haemoglobin
values of 2g/dl or
more, compared
with the last postop vaue, or a
need for blood
transfusion, or if it
was
retroperitoneal or
intrcranial
Control: Mean age:
66.2±11.5
M/F:15/23
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Effect size
Int: 12±2 dys
Control: 12±3 dys
p value: Not
significant
DRAFT FOR CONSULTATION
Heparin – extended duration
Bibliographic
reference
Kolb et al,
293
2003
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 310
randomised
Intervention
: n = 146
Control: n =
127
15
withdrawn
from int.
and 22
from cont.
groups.
Patients
characteristics
Type of surgery:
Hip arthroplasty,
knee arthroplasty,
hip fracture surgery
Intervention
Type: Extended (6wk)
LWMH (certoparin)
Dose: 3000 U
Intervention: Mean Timing: begun
perioperatively and
age: 78.1±8.4 yrs
repeated daily until
M/F:25/136
nd
42 day post-op
Additional noncomparative
prophylaxis:
Not reported
Comparison
Type: LMWH
(certoparin) +
placebo
Dose: 3000 U
Timing: begun
perioperatively
and repeated daily
until 14th day
post-op. Then
placebo for 28
days.
Length of
follow up
Outcome
measures
Both
groups: 42
days postop
DVT Confirmed
by: Duplex US
performed weekly
between days 14
and 42 post-op.
PVT Confirmed
by: Duplex US
performed weekly
between days 14
and 42 post-op.
Effect size
Comments
Int: 7/146
Control: 17/127
p value: 0.0172
Comments:
Coagulation
parameters (fibrin
monomers, Ddimers) also
measured. MultiIntention-to-treat:
centre trial across
Int: 7/161
13 centres in
Control: 17/149
Germany and
p value: 0.0316
Czech Republic.
Int: 2/146
Control: 17/147 (11 Patients were
of which also had a randomised after
the initial, 14 day,
distal VT)
open-label period.
p value: 0.0005
25 patients (6.9%)
excluded prior to
Per-protocol
randomisation due
analysis
to thromboembolic
p value:
complications.
(Significant/Not
significant)
ITT analysis
P value:
Control: Mean age:
75.8±8.4
M/F:29/120
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
373 of 648
PE
Confirmed
by: Not routinely
assessed. Clinical
suspicion
investigated with
angiography,
spiral CT or V/Q
scan
Int: 0/147
Control: 2/127
p value: 0.2139
Not reported:
Bleeding, QoL, LoS
Fatal PE
Confirmed by:
autopsy
Int: 0/161
Control: 0/149
p value: N/A
Funding: Study
partly sponsored by
Novartis.
DRAFT FOR CONSULTATION
Heparin – extended duration
Bibliographic
reference
Lausen et al,
316
1998
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 176
randomised
(data for
118)
Intervention
: n = 58
Control: n =
60
(58
excluded,
29 from
each
group)
Patients
characteristics
Type of surgery:
Major general
surgery (major
elective abdominal
or noncardiothoracic
operations)
Intervention
Comparison
Length of
follow up
Outcome
measures
Effect size
Type: Extended
duration LMWH
(tinzaparin) Dose:
3500 IU
Type: LMWH
DVT Confirmed
Int: 3/58
Both
(tinzaparin) Dose: groups: 28 by: Bilateral
Control: 6/60
3500 IU
ascending
p value: 0.49
days
th
venography of 28
post-op day
Timing: : Begun preop and repeated once
daily for 4 weeks
Timing: Begun
pre-op and
repeated once
th
daily until 7 postop day
Proximal DVT
Int: 0/58
Confirmed by:
Control: 0/60
Bilateral
p value: N/A
ascending
th
venography of 28
post-op day
Additional noncomparative
prophylaxis:
Thigh-length
stockings during
st
1 week post-op
Intraoperative
blood loss
Int: Mean 900 ml
(range 0-900)
Control: 600 ml
(range 0-3500
p value: not
reported
Intraoperative
transfusion
requirements
Int: Mean 1.4 units
(range 0-12)
Control: Mean 0.9
units (range 0-9)
p value: not
reported
Post-operative
transfusion
requirements
Int: Mean 1.2
(range 0-8)
Control: Mean (0-8)
p value: Not
reported
Length of
Hospital Stay
Int: Median 15 dys
Control: 14 days
p value: Not
reported
Duration of
surgery:
Intervention: Median
3hr (range 0.5-8.5),
control: Median 3.25 Additional noncomparative
hr (range 0.75-6)
prophylaxis: Thighlength stockings during
Age and gender:
1st week post-op
Intervention:
Median age: 68 yrs
(range 37-84)
M/F:31/27
Control: Median
age: 68.6 yrs
(range29-87)
M/F:33/27
Pre-existing risk
factors: varicose
veins, HRT (no
significant
differences between
groups), malignancy.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
374 of 648
Comments
Comments:
Patients
randomised 7days
post-op. Clinical
suspicion of PE in
two patients (but
not verified by
objective methods).
Not reported: PE,
PTS, QoL
Funding:
Supported by
grants from
Bispebjerg
University Hospital,
the Beckett
Foundation, Novo
Nordisk A/S, Bruel
and Kjaer DK,
Schering Denmark.
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Length of
follow up
Outcome
measures
Survival
(Denominator is
no. of patients
randomised).
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
375 of 648
Effect size
Int: 81/87
Control: 84/89
p value: 0.7651
Comments
DRAFT FOR CONSULTATION
Evidence Table 50: LMWH vs UFH
Bibliographic
reference
Koch 1997
(11 studies)
66,141,169,199,313,31
4,325,370,409,424,497
Study
Type
Evidenc
e level
Systemat 1+
ic Review
No. of
patients
Total: 3608
Int: 1800
Cont: 1808
Patients
characteristics
Type of surgery:
11 orthopaedic
studies
Intervention
Comparison
LMWH
UFH
Dose: Ranged
between 3100-5000
Anti X-a unitls
Dose: 5000-7500
IU
Timing: Initiated
preoperatively at
diagnosis to
postoperatively 12-24
hours.
Timing: Initiated
preoperatively at
diagnosis to
postoperatively
12-24 hours.
Duration: Ranged
from greater than 6 to
14 days.
Duration: Ranged
from greater than
6 to 14 days
Additional noncomparative
prophylaxis:
GCS (1 study)
Leg bandages (1
study)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Additional noncomparative
prophylaxis:
GCS (1 study)
Leg bandages (1
study
376 of 648
Length of
follow up
NR
Outcome
measures
Effect size
Comments
DVT confirmed by
radiofbrinogen
update test or
phlebography.
Int: 250/1761
Cont: 284/1765
p value: 0.1212
Funding: grant
from Deutsche
Forschungsgemein
schaft.
Proximal DVT
Int: 84/1430
Cont: 120/1432
p value: 0.0017
Not reported: QoL,
LoS, PTS.
PE (observed)
Int: 18/1570
Cont: 33/1570
p value: 0.0471
Major bleeding:
Int: 69/1604
Cont: 79/1619
p value: 0.4497
DRAFT FOR CONSULTATION
LMWH vs UFH
Bibliographic
reference
Mismetti
364
2001
48 studies
8,30,35,46,47,59,70,71
,76,86,91,110,115,117,
139,148,170,181,184,1
87,189,202,213,223225,233,234,266,269271,274,275,294,295,2
97,322,328,383,389,39
6,441,445448,455,457,458,521,5
25,543
Study
Type
Evidenc
e level
Systemat 1+
ic review
No. of
patients
Total:
15349
Patients
characteristics
Intervention
Type: LMWH
Type of surgery:
General (36 studies)
Comparison
UFH
Additional noncomparative
Timing:
Postoperative (1 study) prophylaxis:
none
Preoperative (47
T (thoracic? 1 study) studies)
Gynecology (5
studies)
Mixed (6 studies)
Duration:
3-10 days
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
377 of 648
Length of
follow up
7 days – 3
months
Outcome
measures
Effect size
DVT FUT, FUT +
veno,
Thermography,
IPG, Doppler.
Int: 310/8100
Cont: 350/7319
p value: 0.0036
PE
Int: 13/3895
Cont: 20/3857
p value: 0.2264
Major bleeding
Int: 219/7473
Cont: 245/6986
p value: 0.0528
Proximal DVT
Int: 6/1466
Cont: 20/1437
p value: 0.0053
Comments
Not reported:
LoS, QoL, PTS
Funding: SanofiSynthelabo grant
DRAFT FOR CONSULTATION
LMWH vs UFH
Bibliographic
reference
Study
Type
Avikainen et al RCT
24
1995
Evidenc
e level
1+
No. of
patients
Total: 167
Intervention
: n = 83
(DVT
assessed in
79)
Control: n =
84 (DVT
assessed in
79)
Patients
characteristics
Type of surgery:
Hip replacement
(& Duration of
surgery)
Intervention
Type: LMWH
(Enoxaparin)
40mg/0.4 ml
Dose:
Intervention: Mean Timing: Begun 12hrs
pre-op and repeated
age: 65 (range 2786) yrs M/F:30/53 daily for 10 days
Control: Mean age:
66 (range 34-86)
M/F:25/59
Pre-existing risk
factors: varicose
veins
Comparison
Type: UFH
Dose: 5000 IU
Timing: Begun
2hrs pre-op and
repeated twice
daily for 10 days
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
378 of 648
Length of
follow up
Both
groups:
Until
discharge
th
(10 postop - ).
Outcome
measures
Effect size
DVT Confirmed
th
by: US on 10-14
post-op day.
US results for 158
patients
Int: 1/79
Control: 4/79
p value: >0.05
PVT Confirmed
th
by: US on 10-14
post-op day.
Int: 1/79
Control: 4/79
p value: >0.05
PE
Confirmed
by: Not routinely
assessed.
Symptomatic
confirmed by V/Q
scan
All patients:
Int: 0/84
Control: 1/83
p value: 0.4970
Comments
Also reported:
perioperative and
postoperative
blood loss,
transfusion
requirements
Not reported: PTS,
QoL, survival, LoS,
funding
DRAFT FOR CONSULTATION
LMWH vs UFH
Bibliographic
reference
Beghi et al
37
1993
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Type of surgery:
Total: 39
Intervention Open heart surgery
: n = 20
Control: n =
19
Duration of
surgery:
Intervention:
209±11.82 min
Control: 224±13.37
min
Intervention
Length of
follow up
Comparison
Type: LMWH (Fluxum) Type: LDUH
Dose: 3200 IU
Dose: 5000 IU
Timing: Begun 1st day
post-op and repeated
three times daily until
th
4 post-op day
Timing: Begun 1
day post-op and
repeated daily
th
until 4 post-op
day
Both
DVT Confirmed
groups: 11 by: Doppler US
th
days
(on 7 post-op
day?)
st
Effect size
Int: 0/20
Control: 0/19
p value: N/A
Comments
Comments:
Patients with
cardiac disease
requiring postoperative oral
anticoagulation
were not included
in the study.
Not reported:
Proximal DVT, PE,
PTS, QoL, survival,
LoS
Additional noncomparative
Age & Gender:
prophylaxis:
Intervention: Mean Not reported
age: 60.2±1.94 yrs
M/F:15/5
Also reported:
units of transfused
blood per patient;
volume of bleeding;
haemoglobin
g/100cc; platelets
n/mm3
Control: Mean age:
60.5±2.39 yrs M/F:
16/3
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Outcome
measures
379 of 648
DRAFT FOR CONSULTATION
LMWH vs UFH
Bibliographic
reference
Colwell et al,
109
1995
Study
Type
Multicent
re RCT
involving
25
centres.
Evidenc
e level
1+
No. of
patients
Total:
453
Patients
characteristics
Type of surgery:
Elective knee
arthroplasty
Intervention
:
Intervention: Mean
n = 228
age: 67.5± 9.5 yrs
Control:
M/F:107/121
n = 225
Control: Mean age:
68.6± 8.8 yrs
M/F:91/134
Intervention
Comparison
Type:
Enoxaparin 30mg
every 12 hours
Type:
Unfractionated
heparin 5000 units
every 8 hours
Timing:
started day of surgery
(within 8hours of
surgical closure) and
continued for a
minimum of 4 days
and maximum of 14
days.
Timing:
started day of
surgery (within
8hours of surgical
closure) and
continued for a
minimum of 4
days and
maximum of 14
days.
Additional noncomparative
prophylaxis:
none reported
Additional noncomparative
prophylaxis:
none reported
Length of
follow up
Treatment
period up to
14 days,
follow up
approx 3
weeks after
last dose
Outcome
measures
Effect size
DVT Confirmed
by: US or
venography
Int: 54/145
Control: 74/143
p value: 0.02
PE
Confirmed
by: ventilation
perfusion scan or
pulmonary
angiography
Int: 0/145
Control: 1/143
p value: 0.4965
Total
hemorrhage
episodes
Int: 46/228
Control: 52/225
p value: 0.2470
Major
hemorrhage
episodes (major
not defined)
Int: 3/228
Control: 3/225
p value: 1.000
Minor
hemorrhage
episodes (minor
not defined)
Int: 43/228
Control: 49/225
p value: 0.4840
Int: 7±2 days
Length of
range: 1-14 days
Hospital Stay
(Mean±SD, range) Control: 7.1±2 days
range: 2-15 days
p value: not
significant
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
380 of 648
Comments
Comments:
Only 63.6% of
patients evaluated.
Multicentre study,
not all centres used
a valid diagnostic
technique (same
numbers in each
group). An intention
to treat analysis
was followed.
Results are
available for
patients diagnosed
by valid test alone
as well as all
patients.
Also reported:
incidence of DVTs
diagnosed from all
means including
symptomatic,
broken down into
distal and proximal.
Not reported:
PTS, QoL, length of
hospital stay,
survival.
Funding:
not reported
DRAFT FOR CONSULTATION
LMWH vs UFH
Bibliographic
reference
Farkas et al
151
1993
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 233
Intervention
: n = 122
Control: n =
111
Type of surgery:
Vascular surgery –
aortic or aortoiliac
and
aneurysmectomy;
aorto-femoral
bypass for
269
atherosclerotic
patients
randomised disease; and
femoropopliteal or
, 36
femorodistal bypass.
excluded
Mean duration of
surgery:
Intervention: 4.2±1.4
h Control: 4.2±1.5h
Intervention
Comparison
Length of
follow up
Outcome
measures
Effect size
Type: LMWH
(Enoxaparin) Dose:
2100 IU pre-op, then
4200 IU
1 month
Type:
Unfractionated
heparin Dose:
5000 units pre-op,
7500 units post-op
DVT Confirmed
by: Duplex US,
confirmed by
venography on
7th-10th day postop. Earlier if
clinical suspicion
Int: 10/122
Control: 4/111
p value: Not
significant)
Timing: Begun day
pre-op and repeatedly
th
daily until 7 day postop
Timing: Begun
day pre-op and
repeated twice
th
daily until 7 day
post-op
PE
Confirmed
by: Clinical
suspicion
investigated by
angiogram
Int: 0/122
Control: 0/111
p value: N/A
Additional noncomparative
prophylaxis:
Intraoperative use
of UH (97.4%) or
protamine (9.4%)
was authorised in
both groups
Peoperative red
blood cell units
Int: 3.91±2.79 units
Control: 3.61±1.91
p value: Not
significant
Post-operative
suction drain
volume
Int: 423±438ml
Control:
408±455ml
p
value: Not
significant
Survival
Int: 120 /122
Control: 111/111
p value: not
reported
Intervention: Mean Additional noncomparative
age: 65±11 yrs
prophylaxis:
M/F:101/25
Intraoperative use of
Control: Mean age: UH (94.4%) or
protamine (7.9%) was
64±11 yrs
authorised in both
M/F:99/18
groups
Pre-existing risk
factors: Past history
of VTE, age, obesity,
varicose veins,
COPD (no
significantdiffs
between groups
apart from COPD –
more in LMWH
group, p=0.02).
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
381 of 648
Comments
Comments:
Numbers in each
group for baseline
data do not tally
with text. Arterial
patency also
assessed by duplex
US scanning. No
significant
differences
observed between
groups in terms of
development of
post-op arterial
thrombosis.
Thrombocytopeni
a (which resolved
spontaneously
within 3 days)
reported in 2
LMWH patients.
Not reported: PVT,
PTS, QoL, LoS,
Funding: Trial
supported by grant
from Labaratoires
Pharmuka, France.
DRAFT FOR CONSULTATION
LMWH vs UFH
Bibliographic
reference
Faunø et al
153
1994
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 185
Intervention
: n = 92
Control: n =
93
Patients
characteristics
Type of surgery:
Unilateral knee
replacement
Duration of
operation:
Intervention: 102±24
224
min
patients
randomised Control: 104±20
. 39
Intervention: Mean
excluded
age: 70±10 yrs
(16 LMWH, M/F:38/55
23 UH)
Control: Mean age:
71±11 M/F:35/57
Pre-existing risk
factors: Not
reported
Intervention
Comparison
Type: LMWH
(Enoxaparin) Dose:
40 mg
Type: UH Dose:
5000 IU
Timing: Begun
evening pre-op and
repeated daily until 7th
10 day post-op.
Additional noncomparative
prophylaxis: Short
compression stocking
on involved limb and
long compression
stocking on uninvolved
limb.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
2 months
Outcome
measures
Effect size
DVT Confirmed
by: bilateral
ascending
venography on 7th
9 day post-op
Int: 21/92
Control: 25/93
p value: 0.6 Not
significant
Timing: Begun
evening pre-op
and repeated 3
times daily until 7th
9 day post-op.
PVT Confirmed
by:
bilateral
ascending
venography on 7th
9 day post-op
Int: 3/92
Control: 5/93
p value: Not
reported
Additional noncomparative
prophylaxis:
Short
compression
stocking on
involved limb and
long compression
stocking on
uninvolved limb.
PE
Confirmed
by: Not routinely
assessed. Clinical
suspicion
investigated with
V/Q scan
Int: 0/92
Control: 0/93
TotaI blood loss
Int: 1450 (450-3660)
ml
Control: 1540 (1503750) ml
p value: 0.8 Not
significant
Mean decrease
in haemoglobin
levels
Int: 1.0 millimole/L
Control: 1.1
millimole/L
p value: 0.8 Not
significant
382 of 648
Comments
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
383 of 648
Length of
follow up
Outcome
measures
Effect size
Transfusion
requirements
Int: 497 (0-2500) ml
Control: 480 (02500) ml p value:
0.7
Wound
haematoma
Int: 8/92
Control: 12/93
p value: 0.5
Comments
DRAFT FOR CONSULTATION
LMWH vs UFH
Bibliographic
reference
Horbach et al,
238
1996
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 305
Intervention
n: 152
Control n:
153
Type of surgery:
Patients undergoing
elective hip
replacement
surgery.
Intervention
Type, dose and
timing: One dose daily
of subcutaneous
LMWH (3000 IU of
Certoparin) plus 0.5mg
DHE injections.
Intervention: Mean Prophylaxis started 2
hours before surgery
age: 64.2 ± 10.0
and continued for at
years M/F:72/80
least 14 post operative
Control: Mean age: days or longer if
patient was still
64.9 ± 9.8 years
institutionalised.
M/F:70/83
Pre-existing risk
factors:
Additional noncomparative
Previous
thrombosis: Int: n = prophylaxis:
Not reported
13 Contol: n = 16
Previous PE: Int: n
= 3 Control: n = 6
Varices: Int: n = 69
Control: n = 79
Diabetes mellitus:
Int: n = 10 Control:
n = 8; p=0.498
obesity: Int: n = 5
Control: n = 26
obstructive
pulmonary disease:
Int: n = 3 Control:
n=2
Cardiac
insufficiency: Int: n =
0 Control: n = 1
Malignancy: Int: n =
1 Control: n = 1
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Type, dose and
timing: starting
dose of 15000
IU/day was
increased to a
plateau value of
28,800 ± 7150 IU/
day to maintain
the activated
partial
thromboplastin
time in the
prescribed range
injected
subcutaneously
daily. Prophylaxis
started 2 hours
before surgery
and continued for
at least 14 post
operative days or
longer if patient
was still
institutionalised.
384 of 648
Length of
follow up
14 days
Outcome
measures
VTE total
DVT confirmed by
bilateral
ascending
venography.
Proximal DVT:
Distal DVT:
Effect size
Comments
Study on fixed dose
Int:17/142 (12.0%)
Cont: 14/147 (9.5%) combination of
LMWH with
p=0.50
Dihyroergotamine
Int:17/142
vs adjusted dose
Cont: 13/147;
UFH (starting with
p=0.76
15,000 IU/day and
increased to 28,800
IU/day ±7,150
Int:0/142
IU/day) in
Cont: 0/147
prevention of DVT
Int:15/142
after total hip
Cont: 8/147; p=2.59 replacement.
Proximal and
Distal DVT:
Int:2/142
Cont: 5/147; p=1.21
PE Confirmed by
pulmonal
szintigraphy.
Int:0/142
Cont: 1/147; p=0.87
Also reported:
intraoperative and
postoperative blood
loss, postoperative
transfusions,
revieion of vound,
reoperation due to
bleed ing
complications,
hematoma at
injection site,
patechlal,
DRAFT FOR CONSULTATION
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
385 of 648
DRAFT FOR CONSULTATION
LMWH vs UFH
Bibliographic
reference
Kakkar et al,
273
2000
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 298
Intervention
n: 149
Control n:
149
Patients
characteristics
Intervention
Type, dose and
timing: One dose daily
of subcutaneous
LMWH (3500 IU of
Bemiparin) plus a
placebo injections of
0.9% saline.
Duration of
Prophylaxis started 2
surgery: Int:
hours before surgery
110±55.1
Control: 100±58.7; and continued for at
least 8 post operative
p=0.207
days or longer if
patient was still
Age and gender:
Intervention: Mean institutionalised.
age: 70.4 ± 10.9
years M/F:49/100
Additional nonControl: Mean age: comparative
prophylaxis:
70.5 ± 9.2 years
Not reported
M/F:45/104
Type of surgery:
Patients scheduled
for elective hip
replacement
surgery.
Comparison
4 weeks
Type, dose and
timing: 5000 units
of Calcium
heparin injected
subcutaneously
twice daily.
Prophylaxis
started 2 hours
before surgery
and continued for
at least 8 post
operative days or
longer if patient
was still
institutionalised.
Pre-existing risk
factors:
Previous DVT: Int: n
= 4 Control: n = 12;
p=0.070
Previous PE: Int: n
= 1 Control: n = 3;
p=0.615
Varicose veins: Int:
n = 44 Control: n =
46; p=0.900
Varicose ulcer: Int: n
= 3 Control: n = 6;
p=0.498
obesity: Int: n = 23
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
386 of 648
Outcome
measures
Effect size
VTE total
Int: 9/125 (7.2%)
Cont: 25/134
(18.7%)
p=0.01
DVT confirmed by
bilateral elective
venography.
Int: 9/101 (8.9%)
Cont: 24/116
(20.7%)
p=0.03
Proximal DVT:
Int: 3/101 (3.0%)
Cont: 5/116 (4.3%)
p=0.73
Distal DVT:
Int: 4/101 (4.0%)
Cont: 13/116
(11.2%)
p=0.08
Proximal and
Distal DVT:
Int: 2/101 (2.0%)
Cont: 6/116 (5.2%)
p=0.23
PE Confirmed by
ventilation
perfusion lung
scan.
Int: 1/125 (0.8%)
Cont: 2/134 (1.5%)
p=1.00
Operative blood
loss (median)
Int: 500.0
Control: 610.0;
p= 0.77
PO drain loss
(median)
Int: 350.0
Control: 380.0;
p= 0.97
Patient
transfused
Int: n = 74/149
Control: n =
66/149; p=0.42
Comments
Financially
supported by
Laboratories
Farmaceuticos Rovi
S.A.; (Madrid,
Spain) Who also
provided supply of
LMWH and std
UFH sodium
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Control: n = 27;
p=0.640
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
Outcome
measures
Wound
hematomas
387 of 648
Effect size
Int: n = 8/149
Control: n = 7/149;
p=1.00
Comments
DRAFT FOR CONSULTATION
LMWH vs UFH
Bibliographic
reference
Legnani et al,
321
1990
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 50
Type of surgery:
Gynaecological
Intervention laparotomy patients
(& Duration of
: n = 24
Control: n = surgery)
26
Intervention: Mean
age: 55.6±7.6 yrs
M/F: not reported
Control: Mean age:
55.7±10.5
M/F: not reported
Pre-existing risk
factors:
No previous history
of DVT
Intervention
Type:
4000iu LMWH (Alfa
LMW1-OP 2123)
subcutaneously once
per day
Patients with
malignancy (11/24
patients) and/or
undergoing WertheimMeigs laparotomy
(2/24 patients)
received 4000iu
LMWH subcutaneously
twice daily
Comparison
Type:
5000iu calcium
heparin
(Italfarmaco)
subcutaneously
twice daily
Patients with
malignancy (12/26
patients) and/or
undergoing
Wertheim-Meigs
laparotomy (2/26
patients) received
5000iu calcium
heparin
subcutaneously
three times daily
Timing:
started 2 hours
preoperatively and
continued until
postoperative day 7
Timing:
started 2 hours
preoperatively and
continued until
postoperative day
7
Additional noncomparative
prophylaxis:
none reported
Additional noncomparative
prophylaxis:
none reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
388 of 648
Length of
follow up
8 days
postoperatively
Outcome
measures
Effect size
DVT Confirmed
by:
125
I FUT
Int: 5/24
Contol: 5/26
p value: 1.0000
Fatal PE (see
comments):
Int: 0/24
Control: 0/26
p value: N/A
Survival (see
comments)
Int: 24/24
Control: 26/26
p value: N/A
Comments
Comments:
PE and survival not
reported but it
appears all patients
completed the
study as none lost
to follow-up prior to
discharge.
Not reported:
PE
PTS
bleeding
QoL
Funding:
not reported
DRAFT FOR CONSULTATION
LMWH vs UFH
Bibliographic
reference
McLeod et al,
357
2001
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Type of surgery:
Total: 936
Intervention Patients undergoing
colorectal surgery.
n: 468
Control n:
468
Intervention
Type, dose and
timing: One dose daily
of subcutaneous
LMWH (40 mg of
Enoxaparin) plus 2
placebo injections of
0.9% saline every 8
hours for up to 10 days
after surgery.
Prophylaxis started 2
hours before surgery.
Comparison
10 days
Type, dose and
timing: 5000 units
of Calcium
heparin injected
subcutaneously
every 8 hours for
10 days.
Prophylaxis
started 2 hours
before surgery.
Intervention: Mean
Additional nonage: 52 ± 18 years
comparative
M/F:376/298
prophylaxis:
Control: Mean age: Not reported
50 ± 17 years
M/F:355/320
Outcome
measures
Effect size
VTE rate was the
same in both
groups
44/468 (9.4%) (95%
CI of the difference,
0 ±3.7%)
DVT confirmed by
bilateral duplex
compression US
or venography.
PE Confirmed by
lung scan or
pulmonary
angiogram
Proximal DVT:
Int: 2.8%
Control: 2.6%
Int: n = 1
Control: 0
Bleeding
complications:
Pre-existing risk
factors:
History of prior
thromboembolism:
Int: n = 14 Control:
n = 19
Malignancy: Int: n =
164 Control: n =
160
Inflammatory bowel
disease: Int: n = 202
Control: n = 211
Rectal procedure:
Int: n = 241
Control: n = 246
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
389 of 648
Major bleeding
Int: n = 18/653
Control: n = 10/643
Minor bleeding
Int: n = 52/653
Control: n = 32/643
Comments
Screening tests
used are not
consistent
through out study.
DRAFT FOR CONSULTATION
LMWH vs UFH
Bibliographic
reference
von
Tempelhoff et
527
al, 2000
Study
Type
RCT
Evidenc
e level
+
No. of
patients
Total: 324
Intervention
n: 160
Control n:
164
Patients
characteristics
Intervention
Type, dose and
timing:
3000 anti-Xa units of
Certoparin injected sub
cutaneously into
Intervention: Mean abdomen once daily
and 2 placebo
age: 60.6 years
injections twice daily.
Control: Mean age: The first active dose
62.6 years
was given 2 hrs
preoperatively and at 8
Pre-existing risk
hour intervals until 7th
factors:
postoperative day.
All oncology patients
Additional noncomparative
prophylaxis:
Not reported
Type of surgery:
Patients scheduled
for primary cancer
surgery.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Length of
follow up
Type, dose and
3-6
timing: 5000 IU
months?
UF Heparin
injected sub
cutaneously into
abdomen thrice
daily.
The first active
dose was given 2
hrs preoperatively
and at 8 hour
intervals until 7th
postoperative day.
390 of 648
Outcome
measures
DVT confirmed by
?
Effect size
Comments
Methods used for
Int: n = 10/160
Control: n = 10/164 screening DVT are
not mentioned.
(37%)
Mortality
Patients who died
post operatively
due to cancer
Int: n = 7/140
Control: n = 3/147
Other than cancer
deaths
Int: n = 1/140
Control: n = 2/147
DRAFT FOR CONSULTATION
LMWH vs UFH
Bibliographic
reference
Ward and
Pradhan,
533
1998
Study
Type
RCT
Evidenc
e level
+
No. of
patients
Patients
characteristics
Total: 552
Intervention
n:271
Control n:
281
Type of surgery:
Women undergoing
major
gynaecological
surgery.
Intervention
Type, dose and
timing: One dose daily
of subcutaneous 5000
LMWH Reviparin
(Fragmin) injection at a
site distant from the
Intervention: Mean surgical site.
Treatment was begun
age: 55 ± 17 years
12 hrs prior to surgery
Control: Mean age: and continued for 5
55 ± 16 years
days or until full activity
was resumed
Pre-existing risk
whichever was longer.
factors:
Previous VTE:
presence indicated
but no figures are
given
Additional noncomparative
prophylaxis: The use
of compression
stockings and
intermittent calf
Malignant disease:
compression devices
Int: n = 222
used by small number
Control: n = 239
of women with
Radical surgery: Int: previous history of
n = 208 Control: n DVT or PE.
= 222
Non radical surgery:
Int: n = 63 Control:
n = 59
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Length of
follow up
6 Weeks
Type, dose and
timing: Twice
daily
subcutaneous
dose of 5000 U
Sodium Heparin.
Injection at a site
distant from the
surgical site.
Treatment was
begun 12 hrs prior
to surgery and
continued for 5
days or until full
activity was
resumed
whichever was
longer.
Additional noncomparative
prophylaxis: The
use of
compression
stockings and
intermittent calf
compression
devices used by
small number of
women with
previous history of
DVT or PE.
391 of 648
Outcome
measures
Effect size
DVT confirmed by
Doppler US or
Venography
Int: n = 0; Control:
n=1
PE Confirmed by
V/Q lung scan.
Int: n = 5; Control:
n=1
Blood
transfusion
Int: n = 57; Control:
n = 39
Comments
DRAFT FOR CONSULTATION
LMWH vs UFH
Bibliographic
reference
Lastoria et al,
315
2006
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 75
M/F: 59/16
Int: 41
Cont: 34
Patients
characteristics
Type of surgery:
Vascular: Major
lower extremity
amputation (30
above-knee and 45
below-knee)
Inclusion criteria:
Patients over 18
years, undergoing
elective or
emergency lowerlimb amputation for
critical-limb
ischemia.
Excluded if had
previous venous
thrombo-embolism,
and patients with
contra-indication for
anticoagulant
prophylaxis.
Intervention
Comparison
LMWH (enoxaparin)
UFH
Dose: 40mg/day
Dose: 5000 IU
(subcutaneously)
Timing: 12 hours
before surgery or in
emergency cases in
the first postoperative
day.
Timing: 12 hours
before surgery or
in emergency
cases in the first
postoperative day.
Duration: During
hospitalisation
Duration: During
hospitalisation
Additional noncomparative
prophylaxis:
Not reported
Additional noncomparative
prophylaxis: Not
reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
392 of 648
Length of
follow up
NR
Outcome
measures
DVT confirmed by
duplex scanning
(5-8 days after
surgery)
Effect size
Int: 4 (9.7%)
Cont: 4 (11.7%)
P=0.92
Comments
Funding: Paulista
State University.
Not reported:
Proximal DVT’s,
PEs, duration of
hospital stay, QoL
or post-thrombotic
syndrome.
Notes:
DVT: 1 bilateral
thrombosis in each
group.
No significant
difference between
interventions in
DVTs in level of
amputation or sex
of patient.
DRAFT FOR CONSULTATION
Evidence Table 51: Patient views on heparin
Bibliographic
reference
Colwell et al,
106
2005
Study
Type
Case
series
Evidenc
e level
3
No. of
patients
Patients
characteristics
Intervention
Type: Self injection of
Type of surgery:
low molecular weight
Primary or revision
elective total hip and heparin (Enoxaparin)
11
knee surgery.
excluded
Dose:
Discharged
Age: 40 to 70 years 30mg per day at 9am
to nursing
and 9pm for
facility: 5
postoperative days 1
Surgery
to 7
cancelled:
40mg per day at 9am
2
for postoperative days
Using
8 to 21
anticoagula
nt: 1
Staff nurses gave first
Retinal
injections and
hemorrhag
explained purpose of
e before
heparin, discussed
surgery: 1
patient's
Withdrew
responsibilities
consent: 2
following discharge.
Patients (or family
member)
demonstrated their
technique.
Total: 61
Comparison
not applicable
Outcome
measures
21 days
postoperati
vely
Concordance
with self
injection
Effect size
22/40 fully
coconcordant:(all
doses within one
hour of scheduled
time)
15/40 partially
coconcordant: (at
least 6 days of 30mg
every 12 hours then
at least 13 days of
40mg once per day.
All doses within 2
hours of scheduled
time)
3/40 non concordant
Comments
Comments:
Funding: not
reported but
manufacturers
supplied a video for
each participant on
injection technique.
Also reported:
No. of patients
understanding the
importance of self
injection
No. of patient
comfortable giving
injection
Mild burning and
stinging at injection
site
Mild bruising at
injection site
Patients also given a
take home self
injection kit that
included and
instructional video
developed by the
manufacturer and
written instructional
materials outlining
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
Not reported:
393 of 648
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
injection technique and
potential side effects.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
394 of 648
Length of
follow up
Outcome
measures
Effect size
Comments
DRAFT FOR CONSULTATION
Patient views on heparin
Bibliographic
reference
Spahn et al,
477
2002
Study
Type
Case
series
Evidenc
e level
3
No. of
patients
Total:
207
Age:
<20 yrs: 26
20-40 yrs:
82
40-60 yrs:
51
>60 yrs: 48
300
patients
included in
the study,
220
returned
the
questionnai
re, 13 were
incomplete.
Patients
characteristics
Type of surgery:
Knee arthroplasty
Intervention
Type:
Injection of low
molecular weight
heparin (Fraxiparin)
Comparison
not applicable
Injection by:
Self: n = 160
Family member or
friends: n = 31
Nursing service: 16
10 days
postoperatively
Outcome
measures
Effect size
Problems with
None: 107/191
self /family
(56%)
member injection Initially: 72/191
(37.7%)
All the time: 12/191
(6.3%)
Perception of
injection 'very
unpleasant'
Injection by:
Self: 18/160 (11%)
Family: 9/31 (29%)
Nurses: 5/16 (31%)
No. self/family
54/191 (28.3%)
member
infection patients
with unsure
prophylaxis
Dose:
Depended on body
weight and further risk
factors.
Instructions were given
by a physician or
qualified nurse.
Patients carried out
first and last injection
in the presence of the
instructor and got a
pack containing 10
syringes, disinfection
swabs and an
information brochure.
34/191 (17.8%)
No. self/family
member
infection patients
who forgot
prophylaxis
25/191 (13.1%)
No. self/family
member
infection patients
discontinued
injections early
Assessment of patient
use by anonymous
questionnaire.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
395 of 648
Comments
Comments:
Not reported
Funding:
Not reported
Also reported:
Not reported:
Not reported
DRAFT FOR CONSULTATION
Evidence Table 52: Fondaparinux vs LMWH
Bibliographic
reference
Agnelli et al,
9
2005
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total:
Interventio
n: n = 1433
Control: n
=1425
Type of surgery:
High risk abdominal
surgery
Duration of surgery:
Int: 2hr 30 (range
23min - 11 hr)
Cont: 2hr 30 (range
16 min - 15 hr
27min)
Intervention:
Median age: 66 (3192) yrs
M/F:788/645
Control: Median
age: 65 (17-93 yrs)
M/F:92/77
Intervention
Type: Fondaparinux
Dose: 2.5 mg once
daily
Timing: Begun 6 hrs
post-op and repeated
daily for 5-9 days.
Placebo injections
given to match LMWH
schedule.
Additional noncomparative
prophylaxis: Use of
GCS permitted. Early
mobilisation strongly
recommended
Pre-existing risk
Factors: Patients
were >60 or >40
with the presence of
an additional risk
factor
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Type: LMWH
(Dalteparin)
Dose: 2500 IU
given 2 hours
before
preoperatively
then 2500 IU
given 12 hours
later.
5000 units given
once daily
thereafter
Timing: Begun
2hrs pre-op and
repeated for 5-9
days.
Placebo injections
given to match
fondaparinux
schedule.
Additional noncomparative
396 of 648
Length of
follow up
Outcome
measures
Venograph
y up until
day 10
postoperati
vely.
DVT Confirmed
by: Bilateral
venography on 5th
10 post-op day
(but no more than
1 day after last
injection).
Int: 4/1024
Control: 59/1018
p value: 0.1 Not
significant
Proximal DVT
Confirmed by: As
above
Int: 5/1076
Control: 5/1077
p value: 1 Not
significant
Bleeding related
complications
Major bleeding:
fatal,
retroperitoneal,
intracranial,
intraspinal, or
involved any other
critical organ,
bleeding leading
to reoperation or
intervention, or a
bleeding index of
2.0 or more.
Int: 49/1433
Control: 34/1425
p value: 0.122 Not
significant
Effect size
Comments
Comments:
Multicentre trial in
131 hospitals in 22
countries. Lower
age limits of patient
groups do not
correspond to
inclusion criteria.
Clinical PE in 5
Fondaparinux and
3 LMWH patients
(of which 3 in each
group were fatal).
LMWH begun postop in some patients
(who received
epidural
anaesthesia)
Not reported:
Objectively
confirmed PE. PTS,
QoL, LoS
Funding:
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
prophylaxis: Use
of GCS permitted.
Early mobilisation
strongly
recommended
Length of
follow up
Outcome
measures
All cause
mortality:
Effect size
On 10th day
Int: 15/1433
Control: 34/1425
p value: 0.0060
Day 32
Int: 32/1433
Control: 55/1425
p value: 0.0122
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
397 of 648
Comments
Sponsored by drug
company (SanofiSynthlabo and NV
organon). 2
company reps on
steering committee.
Data collection and
statistical analysis
performed by
sponsor.
DRAFT FOR CONSULTATION
Fondaparinux vs LMWH
Bibliographic
reference
Bauer et al,
34
2001
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 1049
Interventio
n n: 526
Control n:
523
Patients
characteristics
Intervention
2.5 mg of
Fondaparinux sodium
postoperatively once
daily and a placebo
once daily
subcutaneously till day
5 to 9. Day of surgery
Intervention: Mean is day 1.
age: 67.5, SD:
±10.7; M/F:204/313 Additional noncomparative
Control: Mean age: prophylaxis: The use
of graduated
67.5, SD: ±10.2;
compression stockings
M/F:223/294
and physiotherapy was
recommended
Pre-existing risk
Factors:
History of VTE:
Intervention: 23%
Control: 28%.
Orthopaedic surgery
within the previous
12 months:
Intervention: :87%
Control:: 27%
Type of surgery:
Patients undergoing
elective major knee
surgery.
Duration of surgery:
128 mins, SD: ±42
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
30 mg of
Enoxaparin twice
daily
postoperatively
until day 5 to 9.
Day of surgery is
day 1.
Additional noncomparative
prophylaxis: The
use of graduated
compression
stockings and
physiotherapy was
recommended
398 of 648
Length of
follow up
49 days
Outcome
measures
Effect size
DVT Confirmed
by: systematic
bilateral
ascending
venography
(number of
events/ total
number)
Int: 45/361
Control: 98/361
p value: 0.001; RR:
54.1% (95% CI)
VTE
Int: 45/361
Control: 101/363
p value: <0.001
Reduction in risk
(95% CI) 55.2 (36.2
to 70.2)
Symptomatic
DVT
Int: 3/517
Control: 4/517
p value: 1.000
Non-fatal PE
Confirmed by:
lung scan,
pulmonary
angiography or
helical computed
tomography or at
autopsy
Int: 1/517
Control: 4/517
p value: 0.3738
Fatal PE
Confirmed by:
Int: 0/517
Control: 0/517
p value: N/A
Bleeding leading
to re-operation
Int: 2/517
Control: 1/517
p value: 1.000
Other bleeding –
number (%)
Int: 14/517
Control: 19/517
p value: 0.4797
Postoperative
Int: 222/517
Comments
Funding: The
authors have
served as
consultants to NV
Organon and
Sanofi-Synthelabo
and the study
supported by NVO
& SS.
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
399 of 648
Length of
follow up
Outcome
measures
Effect size
transfusions –
number (%)
Control: 197/517
p value: 0.1284
Death from any
cause - number
(%) Up to day 11
Int: 1/517
Control: 2/517
p value: 1.0000
Death from any
cause - number
(%) Up to day 49
Int: 2/517
Control: 3/517
p value: 1.0000
Comments
DRAFT FOR CONSULTATION
Fondaparinux vs LMWH
Bibliographic
reference
Eriksson et al,
142
2001
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Intervention
Total: 1711
Intervention
n: 849
Control n:
862
Type of surgery:
Patients scheduled
to undergo standard
surgery for fracture
of the upper third of
femur, including
femoral head and
neck within 48 hours
of admission.
Duration of surgery:
104 mins, SD: ±44
2.5 mg of
Fondaparinux sodium
and a placebo. The
first active dose was
given 6±2 hrs
postoperatively and
the second 12 or more
after the first.
Treatment was
scheduled to continue
until day 5 to 9. Day of
surgery is day 1.
Intervention: Mean
Additional nonage: 76.8, SD:
±12.3; M/F:187/644 comparative
prophylaxis: The use
Control: Mean age: of graduated
compression stockings
77.3, SD: ±12.6;
and physiotherapy was
M/F:224/698
recommended
Pre-existing risk
factors:
History of VTE:
Intervention: 29
(3.5%)
Control: 32 (3.8%).
Orthopaedic surgery
within the previous
12 months:
Intervention: 33
(4.0%)
Control:: 26 (3.1%)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Length of
follow up
49 days
40 mg of
Enoxaparin and
placebo.
The first active
dose was given
12±2 hrs
preoperatively and
the second 12 to
24 hours
postoperatively.
Treatment was
scheduled to
continue until day
5 to 9. Day of
surgery is day 1.
Additional noncomparative
prophylaxis: The
use of graduated
compression
stockings and
physiotherapy was
recommended
400 of 648
Outcome
measures
Effect size
DVT Confirmed
by: systematic
bilateral
ascending
venography
(number of
events/ total
number)
Int: 49/624
Control: 117/623
p value: <0.001;
RR: 58.2% (95% CI)
VTE
Int: 52/626
Control: 119/624
p value: < 0.001
Reduction in risk
(95 % CI) 56.4 (39.0
to 70.3)
Symptomatic
DVT
Int: 1/831
Control: 1/840
p value: 1.000
Non fatal PE
Confirmed by:
lung scan,
pulmonary
angiography or
helical computed
tomography or at
autopsy
Int: 1/831
Control: 1/840
p value: 1.000
Fatal PE
Confirmed by:
Int: 2/831
Control: 2/840
p value: 1.000
Fatal bleeding
Int: 0/831
Control: 1/842
p value: 1.000
Bleeding leading
to re-operation
Int: 3/831
Control: 2/842
p value: 0.6851
Minor bleeding –
Int: 34/831
Comments
Funding: The
authors have
served as
consultants to NV
Organon and
Sanofi-Synthelabo
and the study
supported by NVO
& SS.
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
401 of 648
Length of
follow up
Outcome
measures
Effect size
number (%)
Control: 18/842
p value: 0.0240
Postoperative
transfusions –
number (%)
Int: 421/831
Control: 422/842
p value: 0.8450
Death from any
cause - number
(%) Up to day 11
Int: 11/831
Control: 16/842
p value: 0.4386
Death from any
cause - number
(%) Up to day 49
Int: 38/831
Control: 42/842
p value: 0.7317
Comments
DRAFT FOR CONSULTATION
Fondaparinux vs LMWH
Bibliographic
reference
Lassen et al,
310
2002
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Intervention
Total: 2309
Interventio
n n: 1155
Control n:
1154
Type of surgery:
Patients scheduled
for primary elective
total hipreplacement surgery
or revision of at least
one component of a
previously implanted
total hip prosthesis.
Duration of surgery:
2.4 hours, SD: ±0.83
2.5 mg of
Fondaparinux sodium
and a placebo. The
first active dose was
given 6±2 hrs
postoperatively and
the second 12 or more
after the first.
Treatment was
scheduled to continue
until day 5 to 9. Day of
surgery is day 1.
Intervention: Mean
Additional nonage: 67, range: 30comparative
90; M/F:396/512
prophylaxis: The use
Control: Mean age: of graduated
compression stockings
67, range: 24-97;
and physiotherapy was
M/F:402/517
recommended
Pre-existing risk
factors:
History of VTE:
Intervention: 35
(4%) Control: 40
(4%).
Orthopaedic surgery
within the previous
12 months:
Intervention: 85
(9%) Control: 84
(9%)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Length of
follow up
49 days
40 mg of
Enoxaparin and
placebo.
The first active
dose was given
12±2 hrs
preoperatively and
the second 12 to
24 hours
postoperatively.
Treatment was
scheduled to
continue until day
5 to 9. Day of
surgery is day 1.
Additional noncomparative
prophylaxis: The
use of graduated
compression
stockings and
physiotherapy was
recommended
402 of 648
Outcome
measures
Effect size
DVT Confirmed
by: systematic
bilateral
ascending
venography
(number of
events/ total
number)
Int: 36/908
Control: 83/918
p value: <0.0001;
RRR:- 56.1% (95%
CI)
VTE
Int: 37/908
Control: 85/919
p value: < 0.0001
RRR (95 % CI) -55.9
(-72.8 to -33.1)
Symptomatic
DVT
Int: 3/1129
Control: 1/1123
p value: 0.6247
Non fatal PE
Confirmed by:
lung scan,
pulmonary
angiography or
helical computed
tomography or at
autopsy
Int: 2/1129
Control: 2/1123
p value: 1.000
Fatal PE
Confirmed by:
Int: 0/1129
Control: 0/1123
p value: N/A
Fatal bleeding
Int: 0/1140
Control: 0/1133
p value: N/A
Bleeding leading
to re-operation
Int: 5/1140
Control: 3/1133
p value: 0.7261
other bleeding –
number (%)
Int: 44/1140
Control: 38/1133
Comments
Funding: study
supported by NV
Organon and
Sanofi-Synthelabo.
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Length of
follow up
Outcome
measures
Effect size
p value: 0.5743
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
403 of 648
Postoperative
transfusions –
number (%)
Int: 714/1140
Control: 690/1133
p value:
Death from any
cause - number
(%) Up to day 11
Int: 0/1140
Control: 2/1133
p value: 0.4122
Death from any
cause - number
(%) Up to day 49
Int: 2/1140
Control: 4/1133
p value: 0.4122
Comments
DRAFT FOR CONSULTATION
Fondaparinux vs LMWH
Bibliographic
reference
Turpie et al,
512
2002
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 2275
Interventio
n n: 1138
Control n:
1137
Type of surgery:
Patients scheduled
for primary elective
total hipreplacement surgery
or revision of at least
one component of a
previously implanted
total hip prosthesis.
Duration of surgery:
2.42 hours, SD:
±0.98
Intervention
2.5 mg of
Fondaparinux sodium
and a placebo. The
first active dose was
given 4-8 hrs after
surgery and the
second 12 or more
after the first.
Treatment was
scheduled to continue
until day 5 to 9. Day of
surgery is day 1.
Additional nonIntervention: Mean comparative
prophylaxis: The use
age: 67, range: 26of graduated
92; M/F:386/401
compression stockings
Control: Mean age: and physiotherapy was
recommended
67, range: 19-91;
M/F:375/422
Comparison
Outcome
measures
Effect size
49 days
30 mg of
Enoxaparin twice
daily. The first
active dose was
given 4-8 hrs after
surgery and the
second 12 or
more after the
first. Treatment
was scheduled to
continue until day
5 to 9. Day of
surgery is day 1.
DVT Confirmed
by: systematic
bilateral
ascending
venography
(number of
events/ total
number)
Int: 44/784
Control: 65/796
p value: <0.047;
RRR:- 31.3% (95%
CI)
VTE
Int: 48/787
Control: 66/797
p value: 0.099
RRR (95 % CI) -26.3
(-52.8 to -10.8)
Additional noncomparative
prophylaxis: The
use of graduated
compression
stockings and
physiotherapy was
recommended
Symptomatic
DVT
Int: 5/1126
Control: 0/1128
p value: 0.0310
Non fatal PE
Confirmed by:
lung scan,
pulmonary
angiography or
helical computed
tomography or at
autopsy
Int: 5/1126
Control: 0/1128
p value: 0.0310
Fatal PE
Confirmed by:
Int: 0/1126
Control: 1/1128
p value: 1.0000
Fatal bleeding
Int: 0/1128
Control: 0/1129
p value: 1.0000
Bleeding leading
to re-operation
Int: 2/1128
Control: 2/1129
p value: 1.0000
Other bleeding –
number (%)
Int: 17/1128
Control: 24/1129
Pre-existing risk
factors:
History of VTE:
Intervention: 40
(5%) Control: 50
(6%).
Orthopaedic surgery
within the previous
12 months:
Intervention: 99
(13%)
Control: 84 (11%)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
404 of 648
Comments
Funding: study
supported by NV
Organon and
Sanofi-Synthelabo.
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Length of
follow up
Outcome
measures
Effect size
p value: 0.3447
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
405 of 648
Postoperative
transfusions –
number (%)
Int: 593/1128
Control: 555/1128
p value: 0.1192
Death from any
cause - number
(%) Up to day 11
Int: 3/1128
Control: 1/1129
p value: 0.3744
Death from any
cause - number
(%) Up to day 49
Int: 6/1128
Control: 3/1129
p value: 0.3427
Comments
DRAFT FOR CONSULTATION
Evidence Table 53: Fondaparinux extended duration
Bibliographic
reference
Eriksson and
Lassen,
143
2003
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 656
Interventio
n n: 326
Control n:
330
Patients
characteristics
Type of surgery:
Patients undergoing
standard surgery for
fracture of the upper
third of femur,
including femoral
Treatment head & neck were
compliance included if surgery
was planned within
verified:
Interventio 48 hours after
n: 307/326 admission.
Control:
Intervention:
305/330
Median age: 79
(range, 23-94 years;
I patient
M/F:92/235
from
placebo
group
Control: Median
received
Fondaparin age: 79 (range, 2896 years;
ux by
M/F:98/231
mistake.
Intervention
2.5 mg of
Fondaparinux sodium
in 0.5ml water once
daily subcutaneously
till day 6 to 8. Day of
surgery is day 1.
After this open label
period pts were
randomised to receive
either 2.5 mg of
Fondaparinux sodium
or placebo once daily
subcutaneously till day
25 to 31. The first dose
was given less than 2
hours after
randomisation.
Additional noncomparative
prophylaxis: The use
of graduated elastic
stockings was
permitted and early
mobilisation was
strongly
recommended.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Length of
follow up
31 days or
2.5 mg of
32 days?
Fondaparinux
sodium in 0.5ml
water once daily
subcutaneously till
day 6 to 8. Day of
surgery is day 1.
After this open
label period pts
were randomised
to receive either
2.5 mg of
Fondaparinux
sodium or placebo
0.5ml of isotonic
sodium chloride
solution once daily
subcutaneously till
day 25 to 31. The
first dose was
given less than 2
hours after
randomisation.
Additional noncomparative
prophylaxis: The
use of graduated
elastic stockings
was permitted and
early mobilisation
was strongly
recommended.
406 of 648
Outcome
measures
Effect size
DVT Confirmed
by: systematic
ascending
bilateral contrast
venography
Int: 3/208
Control: 74/218
p value: < 0.001
Proximal DVT*
Confirmed by:
systematic
ascending
bilateral contrast
venography
Int: 2/221
Control: 35/222
p value: < 0.001
Symptomatic PE
Confirmed by:
high – probability
lung scanning,
pulmonary
angiography,
spiral computed
tomography or at
autopsy
Int: 1/326
Control: 9/330
p value: 0.02
VTE
Comments
No. of patients
available for
Proximal DVT
analysis was more
than DVT as the
patient was
considered if both
proximal veins were
visualised
regardless of
whether the distal
vein was visualised
or not.
Around a third of
patients in each
arm (int: 118/326,
control: 110/330)
were not included
in the analysis
because they had
no VTE
Int: 3/208 (1.4%)
assessment or
Control: 77/220
(35%)
p value: inadequate VTE
assessment.
< 0.001
Bleeding leading
to reopertion
Int: 2/327
Control: 2/329
p value: 1.0000
Overt bleeding
Int: 6/327
Control: 0/329
p value: 0.0150
Funding: Grant
from Sanofisynthelabo, Paris,
France and NV
Organon, Oss, The
Netherlands.
Minor bleeding
Int: 5
Control: 2/329
Not reported:
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Length of
follow up
Outcome
measures
Effect size
p value:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
407 of 648
Transfusion
Int: 29
Control: 20/329
p value:
Death from any
cause
Int: 6
Control: 8
p value:
Comments
DRAFT FOR CONSULTATION
Evidence Table 54: Antiplatelet therapy vs no prophylaxis
Bibliographic
reference
Antiplatelet
Trialists'
Collaboration,
21
1994
Study
Type
Evidenc
e level
Systemat 1+
ic review
No. of
patients
Patients
characteristics
Type of surgery:
Surgical and high
risk medical
patients:
51 trials from
50 papers
General surgery
patients: 24 trials
4 studies with
heparin as
background
prophylaxis
reported
below in next
table.
Traumatic
orthopaedic surgery
patients: 11 trials
Intervention
Antiplatelet therapy:
Comparison
No intervention
Drugs included in
review:
Aspirin
Aspirin & dipyridamole
Ticlopidine
Sulphinpyrazone
Sulocidil
Hydroxychloroquine
Flurbiprofen
unmarketed drugs
Outcome
measures
Majority 1, DVT Confirmed
2 or 3 week by: fibrinogen
studies
uptake test or
venography
Effect size
Int: 604/2551
Control: 711/2286
p value: <0.0001
Int: 65/641
Proximal DVT
Control: 92/556
Confirmed by:
fibrinogen uptake p value: 0.0008
test or venography
Elective orthopaedic
surgery patients: 16
trials
Major bleed
9 studies in
high risk
medical
patients
excluded from
our analysis
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
408 of 648
Int: 22/3264
Control: 11/2781
p value: 0.44
Comments
Trials did not
always what was
considered a major
bleed
Reported
pulmonary emboli
but did not state
how if they were
confirmed.
Not reported:
QoL, survival, LoS,
PTS, funding
DRAFT FOR CONSULTATION
Evidence Table 55: Aspirin adjuvant
Bibliographic
reference
Antiplatelet
Trialists'
Collaboration,
21
1994
3 out of 55
trials
158,331,565
One study
reviewed
separately in
aspirin vs UFH
524
tables below
Study
Type
Evidenc
e level
Systemat 1+
ic review
No. of
patients
273
Patients
characteristics
Type of surgery:
Intervention
Comparison
Aspirin
No intervention
Additional noncomparative
prophylaxis:
Additional noncomparative
prophylaxis:
heparin
heparin
General surgery
patients: 3 trials
Elective orthopaedic
surgery patients: 1
trials
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
409 of 648
Length of
follow up
Outcome
measures
Majority 1, DVT Confirmed
2 or 3 week by: fibrinogen
studies
uptake test or
venography
Effect size
Int: 21/132
Control: 31/131
p value: 0.11
Int: 5/132
Proximal DVT
Control: 11/131
Confirmed by:
fibrinogen uptake p value: 0.15
test or venography
Major bleed
Int: 5/132
Control: 1/131
p value: 0.16
Comments
Trials did not
always what was
considered a major
bleed
Reported
pulmonary emboli
but did not state
how if they were
confirmed.
Not reported:
QoL, survival, LoS,
PTS, funding
DRAFT FOR CONSULTATION
Aspirin adjuvant
Bibliographic
reference
Monreal et al,
371
1995
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Intervention
Type of surgery:
Type: Aspirin
Hip fracture and
Dose: 200mg 3 times
elective hip
daily with meals
replacement patients
Int: 151
Timing:
Control:
Intervention:
Elective hip
154
Mean +SD age: 75
replacement patients
started evening before
also group +14 yrs
operation, hip fracture
of
M/F:53/98
patients started
154receivin
immediately after
g triflusal,
Control:
operation. Both
data not
Mean +SD age: 72
continued until 9th
extracted.
+15 yrs
M/F:67/87
postoperative day
No. of
patients
Pre-existing risk
Additional nonreceiving
factors:
comparative
correct
Previous DVT: 10
prophylaxis:
prophylaxis intervention, 6
Unfractionated
:
control
heparin 7500IU
Int: 148
Leg varicosities: 48 subcutaneously started
Cont: 153
intervention, 45
2 hours before surgery
control
and continued at 12
hour intervals for 10
days.
Total: 459
Comparison
Type: placebo 3
times daily with
meals
Timing:
Elective hip
replacement
patients started
evening before
operation, hip
fracture patients
started
immediately after
operation. Both
continued until 9th
postoperative day
Additional noncomparative
prophylaxis:
Unfractionated
heparin 7500IU
subcutaneously
started 2 hours
before surgery
and continued at
12 hour intervals
for 10 days.
Length of
follow up
th
8
postoperati
ve day for
scans
followed up
for 31
postoperati
ve days
Outcome
measures
Effect size
DVT Confirmed
by: US scanning
or venography
Int: 27/151
Control: 27/154
p value: 1.0000
Proximal DVT
Confirmed by: US
scanning or
venography
Int: 14/151
Control: 13/154
p value: 1.0000
Distal DVT
Confirmed by: US
scanning or
venography
Int: 11/151
Control: 14/154
p value: 0.6775
Symptomatic PE
Confirmed by:
ventilation
perfusion lung
scan
Int: 8/151
Control: 8/154
p value: 1.000
Fatal PE
Confirmed by:
necropsy,
ventilation
perfusion lung
scan before death
or venographic
documentation of
DVT in lower
limbs
Int: 2/151
Control: 1/154
p value: 0.6201
Number of
patients
receiving
transfusion
Int: 58/151
Control: 47/154
p value: 0.1507
Int: 3/151
Number of
people with overt Control: 5/154
p value: 0.7230
bleeding
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
410 of 648
Comments
Comments:
Not reported:
PTS, QoL, length of
hospital stay
Also reported:
Mean red cell units
transfused
preoperatively and
postoperatively
Funding:
not reported
DRAFT FOR CONSULTATION
Aspirin adjuvant
Bibliographic
reference
PE Prevention
(PEP) Trial
Collaborative
418
Group
Hip fracture
patients
Study
Type
Evidenc
e level
1+
Multicentre
RCT
covering
5
countries
No. of
patients
Total:
13,356
Intervention
:
6679
Control:
6677
PEP trial
also
included
elective
arthroplasty
patients.
Total no. of
patients in
both parts
of trail:
17,444
Intervention
:
n = 8726
Control:
n = 8718
Patients
characteristics
Type of surgery:
Hip fracture patients
Participants with a
clear indication or
contraindication to
aspirin were
excluded.
Mean age: 79 years
79% women
Pre-existing risk
factors:
none stated
Intervention
Type: Aspirin
Dose: 160mg daily
Timing:
35 days started as
soon as possible after
admission and prior to
surgery
Additional noncomparative
prophylaxis:
UFH =1207
LMWH =1761
Stockings = 2026
Regional
anaesthesia =2290
Comparison
Length of
follow up
35 days for
mortality or
up to end of
hospital
stay for
Timing:
35 days started as morbidity
soon as possible
after admission
and prior to
surgery
Type: Placebo
matching aspirin
in appearance
Additional noncomparative
prophylaxis:
UFH =1225
LMWH =1663
Stockings = 1969
Regional
Aspirin or non-steriodal anaesthesia
=2313
anti-inflammatory
drugs within 48 hours
Aspirin or nonbefore randomisation
by 9% (figure for both steriodal antiinflammatory
groups, aspirin and
drugs within 48
placebo)
hours before
randomisation by
9% (figure for both
groups, aspirin
and placebo)
Outcome
measures
PE
Confirmed
by (see
comments)
Effect size
Int: 46/6679
Control: 81/6677
p value: 0.02
Int: 18/6679
Fatal PE
Confirmed by (see Control: 43/6677
p value: 0.0013
comments)
result significant
Int: 69/6679
Symptomatic*
DVT Confirmed by Control: 97/6677
p value: 0.0289
venography or
"other objective
test"
Int: 105/6679
Any venous
thromboembolis Control: 165/6677
p value: 0.0002
m PE or
symptomatic DVT
confirmed by (see
comments)
Fatal bleeding
Int: 13/6679
Control: 15/6677
p value: 0.7107
Bleeding,
requiring
transfusion
Int: 198/6679
Control: 161/6677
p value: 0.0540
Evacuation of
haematoma
Int: 24/6679
Control: 33/6677
p value:(0.2
Postoperative
wound bleed >4
days not
requiring
transfusion
Int: 171/6679
Control: 141/6677
p value: 0.09
Haematemesis or Int: 182/6679
melaena not
Control: 122/6677
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
411 of 648
Comments
Comments:
* DVT data not
routinely screened
for, confirmed by
venography or
"other objective
test". All PEs
confirmed by:
pulmonary
angiogram, high
probabliity
ventilationperfusion scan,
intermediate
probability scan
with venographic
evidence of DVT; or
evidence of PE and
necropsy.
Not reported:
PTS, QoL,
screened DVT;
length of hospital
stay
Also reported:
Results for all
venous
thromboembolism
by additional
prophylaxis
received.
No spinal
haematomas in
patients receiving
regional
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
412 of 648
Length of
follow up
Outcome
measures
Effect size
Comments
requiring
transfusion
p value: 0.0005
anaesthesia
Survival at day
35
Int: 6232/6679
Control: 6216/6677
p value: Not
significant
Mortality day 36
to day 365
Int: 271/6679
Control: 291/6677
p value: 0.3891
Funding:
Bayer AG and
Sterling Winthrop
donated calendarpacked aspirin and
placebo
DRAFT FOR CONSULTATION
Aspirin adjuvant
Bibliographic
reference
Study
Type
PE Prevention Multicent
re RCT
(PEP) Trial
Collaborative
418
Group
Elective hip or
knee
arthroplasty
Evidenc
e level
1+
No. of
patients
Total:
4088
Intervention
:
2047
Control:
2041
PEP trial
also
included
elective
arthroplasty
patients.
Total no. of
patients in
both parts
of trail:
17,444
Intervention
:
n = 8726
Control:
n = 8718
Patients
characteristics
Intervention
Type: Aspirin
Type of surgery:
Elective hip or knee Dose: 160mg daily
arthroplasty patients.
Participants with a
clear indication or
contraindication to
aspirin were
excluded.
Timing:
35 days started as
soon as possible after
admission and prior to
surgery
Mean age: 67 years
53% women
Additional noncomparative
prophylaxis:
Pre-existing risk
factors:
none stated
Aspirin or non-steriodal
anti-inflammatory
drugs within 48 hours
before randomisation
=501
Proportion of
participants taking
additional prophylaxis
across both arms:
Non-study aspirin 27%
Non-steriodal antiinflammatory drugs
27%
Unfractionated heparin
2%
Low molecular weight
heparin 35%
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Length of
follow up
35 days for
mortality or
up to end of
hospital
Timing:
stay for
35 days started as morbidity
soon as possible
after admission
and prior to
surgery
Type: Placebo
matching aspirin
in appearance
Additional noncomparative
prophylaxis:
Aspirin or nonsteriodal antiinflammatory
drugs within 48
hours before
randomisation
=520
Proportion of
participants taking
additional
prophylaxis across
both arms:
Non-study aspirin
27%
Non-steriodal antiinflammatory
drugs 27%
Unfractionated
heparin 2%
Low molecular
weight heparin
413 of 648
Outcome
measures
PE Confirmed by
(see comments)
Effect size
Comments
Int: 9/2047
Control: 10/2041
p value: 0.8232
Comments:
* DVT data not
routinely screened
for, confirmed by
Fatal PE
Int: 1/2047
venography or
Confirmed by (see Control: 2/2041
"other objective
comments)
Hazard ratio (95%
CI): 0.50 (0.04-5.49) test". All PEs
confirmed by:
Symptomatic*
Int: 15/2047
pulmonary
DVT Confirmed by Control: 19/2041
angiogram, high
venography or
Hazard ratio (95%
probabliity
"other objective
CI): 0.78 (0.40-1.53) ventilationtest"
perfusion scan,
intermediate
Bleeding,
Int: 64/2047
probability scan
requiring
Control: 75/2041
with venographic
transfusion
p value: not
evidence of DVT; or
significant
evidence of PE and
Evacuation of
Int: 16/2047
necropsy.
haematoma
Control: 8/2041
p value: 0.10
Not reported:
Survival at day
35
Int: 2038/2047
Control: 2030/2041
p value: not
significant
PTS, QoL,
screened DVT;
length of hospital
stay
Funding:
Bayer AG and
Sterling Winthrop
donated calendarpacked aspirin and
placebo
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
35%
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
414 of 648
Length of
follow up
Outcome
measures
Effect size
Comments
DRAFT FOR CONSULTATION
Aspirin adjuvant
Bibliographic
reference
Study
Type
Woolson et al, RCT
558
1991
Evidenc
e level
1+
No. of
patients
Total:
196
patients
217
operations
Int 1:
69 patients
and
operations
Int 2:
73 patients
and 76
operations
Cont:
70 patients
72
operations
(see
comments
)
Patients
characteristics
Type of surgery:
Total hip
replacement
(primary or revision)
Intervention 1
average age: 67.9
M/F 31/38
Intervention 1
average age: 66.3
M/F 27/66
Control
average age: 62.3
M/F 35/35
Pre-existing risk
factors:
Intervention:history
of DVT 10/69,
varicose veins 9/69
Control: history of
DVT 4/72, varicose
veins 5/72
Intervention
Intervention 1:
Type: Warfarin + IPCD
+ GCS
Dose: 7.5 or 10mg on
evening before
surgery, then adjusted
to maintain
prothrombin time
between 14 and 16
seconds.
Intervention 2:
Type: Thigh-length
Intermittent pneumatic
compression and
graduated elastic
stockings.
Comparison
Type:Aspirin +
IPCD + GCS
Dose: 650mg
twice per day
Timing:
Started evening
before surgery
and until
discharge .
Intervention
until
discharge,
followed up
for 3
months
Outcome
measures
Int 1: 6/69
Int 2: 9/76
Control: 7/72
p value: not
significant
Symptomatic PE
Confirmed by
ventilation
perfusion scan*
Int 1: 0/69
Int 2: 0/76
Control: 1/72
p value: not
significant
Total blood loss
(ml)
Int 1: 1564 (n = 69)
Int 2: 1539 (n = 76)
Control: 1595 (n =
72)
p value: not
significant
LoS (days)
Additional noncomparative
prophylaxis:
Not reported
Effect size
Proximal DVT
Confirmed by
venography or
ultrasonograpy
Total blood
replacement
(units)
Timing:
Warfarin started
evening before
surgery, IPCD and
stockings started at
surgery, both
continued until
discharge .
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
Int: 2.8 (n = 69)
Int 2: 2.7 (n = 76)
Control: 2.9 (n =
72)
p value: not
significant
Int: 9 (n = 69)
Int 2: 10 (n = 76)
Control: 9 (n = 72)
p value: not
significant
Comments
Out of 196 patients,
20 had bilateral hip
replacement, 1 had
both procedures in
the same operation,
18 had at least one
week between
procedures, 1 had
bilateral procedure
and a revision at a
later date. All of
these are included
in the total to make
217 operations
*DVT screened
whilst in hospital,
symptomatic PE
followed for 3
months.
Not reported:
All DVTs, QoL,
PTS, survival
Also reported:
Symptomatic DVTs
by operation,
prothrombin time
Funding:
reports: no
commercial funding
415 of 648
DRAFT FOR CONSULTATION
Evidence Table 56: Aspirin dose
Bibliographic
reference
Antiplatelet
Trialists'
Collaboration,
21
1994
3 out of 55
trials
11,209,355
Study
Type
Evidenc
e level
Systemat 1+
ic review
No. of
patients
184
Patients
characteristics
Type of surgery:
Elective orthopaedic
Intervention
Comparison
Higher dose aspirin
Lower dose
aspirin
Additional noncomparative
prophylaxis:
Additional noncomparative
prophylaxis:
None reported
None reported
Length of
follow up
Majority 1
or 2 week
studies
Outcome
measures
Effect size
DVT Confirmed
by: fibrinogen
uptake test or
venography
Int: 32/93
Control: 34/91
p value: 0.65
(3 studies)
Major bleed
Int: 0/43
Control: 1/41
p value: 0.43
(2 studies)
Comments
Not stated what
was considered a
major bleed
Reported
pulmonary emboli
but did not state
how if they were
confirmed.
Not reported:
QoL, survival, LoS,
PTS, funding
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
416 of 648
DRAFT FOR CONSULTATION
Evidence Table 57: Aspirin vs unfractionated heparin
Bibliographic
reference
Dechavanne
127
et al, 1975
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 60
Type of surgery:
Hip replacement for
Intervention patients with
osteoarthritis
:
n = 20
Intervention:
Control:
Average age: 67 yrs
n = 20
M/F:9/11
rd
(3 arm of
study for no Control:
intervention Average age: 62 yrs
M/F:9/11
n = 20)
Pre-existing risk
factors:
Obesity: Int: 4/20
Control: 1/20
Previous DVT: Int:
1/20 Control: 1/20
Previous PE: Int:
1/20 Control: 1/20
Varicose veins: Int:
6/20, Control: 8/20
Intervention
Type: aspirin
Dose: 1.5g/day and
dipyridamole
150mg/day
Timing:
Started day before
surgery and continued
until postoperative day
10
Additional noncomparative
prophylaxis:
none stated
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Length of
follow up
15 days
Type:
postunfractionated
operatively
heparin
Dose: 5000 IU
every 12 hours for
first 48 hours
post-operatively,
then every 8 hours
until postoperative
day 8,
progressively
decreased until
stopped on postoperative day 15
Timing:
Started 2 hours
preoperatively
continued until
postoperative day
15
Additional noncomparative
prophylaxis:
none stated
417 of 648
Outcome
measures
DVT Confirmed
by 125 I-labelled
fibrinogen test.
Effect size
Int: 10/20
Control: 1/20
p value: 0.01
Comments
Not reported:
PE, PTS, no. of
major bleeding
episodes, QoL,
length of hospital
stay, survival
Also reported:
mean blood loss
from drainage
procedures
Funding not
reported
DRAFT FOR CONSULTATION
Aspirin vs unfractionated heparin
Bibliographic
reference
Josefsson et
264
al, 1987
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total 82
Type of surgery:
Hip replacement
Intervention patients >50 years
of age
:
n = 40
Mean age and
Control:
gender not given
n = 42
Pre-existing risk
factors:
none stated
Intervention
Comparison
Type: aspirin
Dose: 1.5g twice daily
Type:
dyhydroergotamin
e-0.5mg with
heparin 5000 IU
Timing:
started 24 hours
preoperatively,
continued twice daily
for 9 days
Additional noncomparative
prophylaxis:
ted stockings applied
immediately after
surgery and continued
until discharge,
physiotherapy and
weight bearing started
on postoperative day 1
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Timing:
started 2 hours
preoperatively,
continued twice
daily for 9 days
Additional noncomparative
prophylaxis:
ted stockings
applied
immediately after
surgery and
continued until
discharge,
physiotherapy and
weight bearing
started on
postoperative day
1
418 of 648
Length of
follow up
9 days
postoperati
vely
Outcome
measures
Effect size
DVT Confirmed
by: I-125
fibrinogen test
Int: 5/40
Control: 3/42
p value: 0.4772
PE Confirmed
by: lung perfusion
scintigraphy
Int: 4/40
Control: 3/42
p value: 0.7091
Episodes of
major bleeding
Int: 0/40
Control: 0/42
p value: N/A
Comments
Not reported
PTS, QoL, survival,
length of hospital
stay
Also reported
mean preoperative
and postoperative
blood loss and
compensation rates
Funding: not
reported
DRAFT FOR CONSULTATION
Aspirin vs unfractionated heparin
Bibliographic
reference
Loew et al,
331
1977
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total 187
randomised
. 10
excluded.
Intervention
:
n = 63
Control:
n = 57
rd
(3 arm of
57 patients
receiving
aspirin and
heparin not
reported
here)
Patients
characteristics
Intervention
Comparison
Type of surgery:
Elective thoracic or
abdominal surgery
patients >50 years
of age.
Type: aspirin
Dose: acetylsalicylic
acid 500mg + placebo
heparin
Type:
unfractionated
heparin
Dose: 5000 units
+ placebo aspirin
Intervention:
Mean +SD age: 62.8
+11.8 yrs
M/F:18/45
Timing:
started the evening
prior to surgery,
continued for 1 week
Timing:
started the
evening prior to
surgery, continued
for 1 week
Control:
Mean +SD age: 58.4
+10.8 yrs
M/F:25/32
Additional noncomparative
prophylaxis:
patients made to walk
as early as possible
Pre-existing risk
factors: Listed as a
similar between
groups (numbers not
given): obesity,
diabetes, varicose
veins, previous
history of
thromboembolism,
postthrombotic
syndtrome and
malignancy
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Additional noncomparative
prophylaxis:
patients made to
walk as early as
possible
Length of
follow up
1 week
postoperati
vely
Outcome
measures
Effect size
DVT Confirmed
by: I-125
fibrinogen test
Int: 19/63
Control: 11/57
p value: 0.2076
Fatal PE
Confirmed by:
autopsy
Int: 0/63
Control: 2/57
p value: 0.2235
Major bleeding
Int: 0/63
Control: 0/57
p value: N/A
Comments
Comments:
not stated in the
paper that
everyone was
screened for DVT
or PE but a
systematic review
comparing the 3rd
arm with the
intervention and
control implies that
alll patients were
screened
Not reported
PE, PTS, QoL,
survival, length of
hospital stay
Funding: not
reported
419 of 648
DRAFT FOR CONSULTATION
Aspirin vs unfractionated heparin
Bibliographic
reference
Plante et al,
410
1979
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total 146
Type of surgery:
Abdominal surgery
Intervention patients
:
Intervention:
n = 38
Average age: 45.1
Control:
yrs
n = 42
M/F:52.6%/47.4%
rd
Average duration of
(3 arm of
62 patients surgery: 146.4 mins
(Aspirin group
receiving
significantly younger
no
intervention than heparin group)
not
Control:
reported
Average age: 58.8
here)
yrs
M/F:40.5%/59.5%
Average duration of
surgery: 159.04
mins
Pre-existing risk
factors:
Obesity:
Int 26.3%
Control 31%
Varicose veins:
Int: 10.5%
Control 19%
Previous phlebitis:
Int: 0%
Control: 4.8%
Intervention
Type: Aspirin &
dipyridamole:
Dose: 600mg lysine
acetylsalicylate
(equivalent to 300mg
aspirin) + 30mg
dipyridamole in an
intravenous infusion
from 2 hours before
surgery then 3 times
daily up to 2.3
postoperative days
THEN 300mg aspirin +
50mg dipyridamole
orally 3 times daily for
a further 8
postoperative days.
Timing:
started 2 hours
preoperatively and
continued for at least 8
days
Comparison
Type:
Unfractionated
heparin:
Dose: 5000IU hog
mucosae calcium
heparinate twice
daily
Timing:
started 2 hours
preoperatively and
continued for at
least 8 days
Additional noncomparative
prophylaxis:
intensive
physiotherapy
from first day of
operation
Additional noncomparative
prophylaxis:
intensive
physiotherapy from
first day of operation
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
420 of 648
Length of
follow up
8
postoperati
ve days
Outcome
measures
DVT Confirmed
by: I-125
fibrinogen test
Effect size
Int: 3/38
Control: 3/42
p value: 1.000
Comments
Comments:
Not reported
PE, PTS, QoL,
survival, length of
hospital stay
Funding: grant
from I.NOT
SIGNIFICANTE.R.
M.
DRAFT FOR CONSULTATION
Aspirin vs unfractionated heparin
Bibliographic
reference
Study
Type
Vinazzer et al, RCT
524
1980
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total 1210 Type of surgery:
Elective abdominal,
Intervention thoracic or vascular
surgery patients >40
:1
years old
n = 404
Intervention
Intervention:
2:
Mean +SD age: 62.0
n = 404
Intervention +11.5 yrs
3:
M/F:202/202
n = 402
Control:
Mean +SD age: 61.4
+10.9 yrs
M/F:212/192
Pre-existing risk
factors:
Obesity:
Int: 35/404
Contol: 39/404
Varicose veins:
Int: 20/404
Control 12/404
Previous
thromboembolism
Int: 7/404
Control 4/404
Intervention
Intervention 1
Type: aspirin +
placebo heparin:
Dose: acetylsalicylic
lysine salt 900mg
(equivalent to 500mg
aspirin) given
intravenously up to
postoperative day
three THEN 500mg
acetylsalicylic acid +
placebo heparin
Comparison
Intervention 2
Type:
unfractionated
heparin + placebo
aspirin:
Dose: beef lung
heparin 5000 units
+ placebo aspirin
Timing:
started on evening
before surgery
and continued
until patients were
Timing:
completely
started on evening
mobilised.
before surgery and
continued until patients Intervention
applied for a
were completely
mobilised. Intervention minimum of 1
applied for a minimum week.
of 1 week.
Additional noncomparative
Intervention 3
prophylaxis:
aspirin plus
unfractionated heparin early ambulation
encouraged but
no physiotherapy
Additional nonand no other
comparative
antithrombotic
prophylaxis:
prophylaxis
early ambulation
encouraged but no
physiotherapy and no
other antithrombotic
prophylaxis
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
421 of 648
Length of
follow up
1 week
Outcome
measures
Effect size
Proximal DVT
Confirmed by:
ultrasonic doppler
Int 1: 14/365
Int 2: 9/378
Int 3: 1/350
p value: not
significant
Fatal PE
Confirmed by
autopsy
Int1: 1/365
Int 2: 1/378
Int 3: 0/402
p value: not
significant
Major bleeds
(Number of bleeds
that lead to a
discontinuation of
prophylaxis)
Int1: 3/404
Int 2: 3/404
p value: not
significant Int 3:
11/350
p value: <0.05
Mean +SD length Int 1:14.0 +7.4 days
of Hospital Stay: Int 2: 14.7 +6.6 days
Int 3: 14.4 +7.2 days
p value: not
significant
Death prior to
day 7 (i.e. within
study period)
Int 1: 17/404
Int 2: 7/404
Int 3: 17/402
p value: <0.05 Int 2
compared to Int 1 &
Int 3
Total no.
dropouts from
study
Int 1: 39/404
Int 2: 26/404
Int 3: 52/402
p value: <0.05
(each intervention
compared to the
others
Comments
Comments:
Diagnosis of DVT
by ultrasonic
doppler detectors in
this study only
permitted analysis
of DVTs above the
knee
Not reported
All DVTs, PEs
confirmed by
suitable diagnostic
test, PTS, QoL.
Funding: not
reported
DRAFT FOR CONSULTATION
Aspirin vs unfractionated heparin
Bibliographic
reference
Zanasi et al,
562
1988
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total 63
Patients
characteristics
Type of surgery:
Orthopaedic surgery
Intervention (majority hip
surgery)
:
n = 19
Intervention:
Control:
Mean +SEM age:
n = 25
69.7 +3.7 yrs
rd
(3 arm of
M/F: 5/14
19 patients
receiving
Control:
defibrotide Mean +SEM age:
not
71.9 +2.2 yrs
reported
M/F:4/21
here)
Pre-existing risk
factors:
none stated
Intervention
Type: aspirin:
Dose: acetylsalicylic
acid 100mg
administered on
alternate days
Timing:
started day before
surgery and continued
for 7 postoperative
days.
Additional noncomparative
prophylaxis:
none stated
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Length of
follow up
7
Type:
postoperati
unfractionated
ve days
heparin:
Dose: beef lung
heparin 5000 units
+ placebo aspirin
Timing:
started day before
surgery and
continued for 7
postoperative
days
Additional noncomparative
prophylaxis:
none stated
422 of 648
Outcome
measures
Effect size
DVT Confirmed
by: FUT
Int: 7/12
Control: 10/25
p value: 0.4821
PE Not stated
how confirmed
Int: 2/12
Control: 1/25
p value: 0.2407
Fatal PE Not
stated how
confirmed
Int: 1/12
Control: 1/25
p value: 0.5495
Comments
Comments:
Diagnosis of DVT
by ultrasonic
doppler detectors in
this study only
permitted analysis
of DVTs above the
knee
Not reported
PTS, QoL, bleeding
complications,
length of hospital
stay
Funding: not
reported
DRAFT FOR CONSULTATION
Evidence Table 58: Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Bailey et al,
26
1991
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total 95
Int: 50
Cont: 45
Patients
characteristics
Intervention
Comparison
Length of
follow up
Control: 5
to 7 days
(also day
Dose: 10mg
diagnostic
before surgery
(7.5mg for women test done
for DVT)
over 70 and
Timing: Applied after
Intervention: Mean surgery in the recovery patients with
Int: 5 to 7
minor
ward and wonr
age: 65.3 (range:
days (also
abnormalitites of
continuously for the
41-88) yrs
day
remainder of the study liver function
M/F:24/26
diagnostic
(except during bathing tests).
test done
Control: Mean age: and physical therapy).
for DVT)
Timing: Evening
64.4 (range: 45-50)
before surgery
Additional nonM/F:22/23
and doses given
comparative
after surgery
prophylaxis: graded
adjusted to
elastic compression
maintain a
stockings applied on
prothrombin time
admission and
at 14-16 seconds.
continued until after
Prothrombin times
discharge.
routinely obtained
by postoperative
day 2 or 3.
Additional noncomparative
prophylaxis:
graded elastic
compression
stockings applied
before and after
surgery
Type of surgery:
total hip replacement
Mean operating time
Int: 184.5 min Cont:
208.5 min
sequential pneumatic
compression device
covering legs and
thighs
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
low dose warfarin
423 of 648
Outcome
measures
DVT Confirmed
by: venography
(see comments)
Effect size
Int: 3/50
Control: 12/45
p value: <0.006
(significant)
Int: 0/50
Major bleeding
Control: 0/45
(defined in the
paper as "clinically p value: N/A
important
bleeding")
Comments
Weight was
significantly greater
in the warfarin
group to the
sequential
compression group.
There was no
significant diference
in weight between
groups for those
who developed
DVT.
Diagnosis of DVT
for those where
there was a lack of
venous access: Bmode Doppler US
and techneciumpyrophosphate redcell labelled nuclear
venogram with
impedance
plethysmography.
Funding: Kendall
Inc supplied the
stockings (not
under
investigation).
Unclear whether
they provided any
other
support/materials
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Blanchard et
64
al, 1999
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 130
Type of surgery:
elective knee
Interventio replacement.
n: 63
Control: 67 Intervention
M/F: 11/52
Mean age: 72
Control
M/F: 20/47
Mean age: 74
Intervention
Comparison
Intermittent pneumatic
plantar compression
(AVIS (Novomedix))
Started 12 hours
preoperatively,
discontinued for
surgery, reapplied after
surgery. Used at all
times except during
walking and
physiotherapy
LMWH
(calcium
nadroparin)
injected
subcutaneously
12 hours
preoperatively the
12 hours
postoperatively
then once per day
for 12 days.
Doses adjusted to
patient's body
weight.
Additional
prophylaxis:
none
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Additional
prophylaxis:
none
424 of 648
Length of
follow up
2 to 3
months
Diagnostic
tests
carried out
8 to 10
days after
surgery.
After
screening
for DVT, all
patients
received
acenocoumarol
for 6 to 8
weeks.
Outcome
measures
Effect size
DVT confirmed by
phlebography or
venous
compression US
Int: 34/63
Cont: 16/.67
p value: <0.01
Proximal DVT
confirmed by
phlebography or
venous
compression US
Int: 4/63
Cont: 2/.67
p value: 0.4
Distal DVT
confirmed by
phlebography or
venous
compression US
Int: 30/63
Cont: 14/.67
p value: <0.005
Symptomatic PE
Int: 0/63
Cont: 0/.67
p value: N/A
Major bleeds
Int: 0/63
Cont: 1/67
p value: not
significant
Comments
At 2 to 3 month
follow up no
patients had
symptomatic DVT
or PE and none
died.
Also reported
Median
intraoperative and
postoperative blood
loss, total blood
transfused.
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Chandhoke et
93
al, 1992
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: n =
100
Intervention
: n = 47
Control: n =
53
Type of surgery:
Patients undergoing
urological surgery
Intervention
Intermetent pneumatic
calf compression (also
refered to as calf
pumps). IPC was
Intervention: Mean instituted
intraoperatively and
age: 67.5±7.1
continued post-op for
M/F:46/1
5days or until patient
became fully ambulant
Intervention: Mean
age: 66.1±6.4
M/F:53/0
Comparison
Low Dose
Warfarin begun
on the night of the
operation
Pre-existing risk
factors:
malignancy
Int: 98%
control:100%. $% of
patients who
received IPC had
DVT
ClarkePearson et al,
101
1993
RCT
1+
Total: 218
gynaecologic
oncology
Intermittent pneumatic
calf compression
Int: 101
Cont: 107
Timing: initiated at
Intervention:
Median age: 57 (22- induction of
anaesthesia and
89) years
continued to 5 days
postoperatively or the
Control:
Median age: 55 (27- patient was
ambulatory.
84) years
Additional noncomparative
prophylaxis: none
reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
Outcome
measures
1 to 2
weeks. The
goal was to
acheivea
prothrombi
n time of
approx
1.5times
the pre-op
value by 3
or 4 days
post-op
DVT (overall)
Confirmed
by:venography
and US
Int: 4/47
Control: 0/53
p value: Not
significant
PE
Confirmed
by:venography
and US
Int: 2/47
Control: 0/53
p value: Not
significant
Bleeding related
complications
Int: 0
Control: 2
p value: Not
significant
Death
Int: 0
Control: 0
p value: Not
significant
diagnostic DVT Confirmed
by: Iodine 125
tests until
Dose and timing: discharge, labelled fibrinogen
followed up
5000 units on
clinically for
admission and
every 8 hours until 30 days
postoperati
surgery, 5000
vely
units
postoperatively
every 8 hours for
7 days.
Low dose heparin
Additional noncomparative
prophylaxis:
none reported
425 of 648
Effect size
Int: 3/101
Control: 6/107
p value: Not
significant
Comments
Not reported:PTS,
QoL, Survival
(total DVTs Int=4
and Cont=7 but one
in each group
clinically detected
after discharge then
confirmed by
venograph
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Coe et al,
103
1978
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 84
in entire
study, 59
for this
comparison
Type of surgery:
Urological (open)
Breakdown of
surgery type given.
Majority were simple
prostatectomies.
Intervention Duration of surgery
: n = 31 (2 not stated.
subsequent
ly dropped Intervention: Mean
age: 55±11 yrs
out)
Compariso M/F:not reported
n: n = 28
Comparison: Mean
age: 63±16
M/F:Not reported
Intervention
Comparison
Type: bilateral calf IPC
device
Dose: 35 - 40 mm
Hg
Type: LDUH
Dose: 5,000
units
subcutaneously
Timing: from
anaesthetic. Mean no
of days treatment 3.2 ±
2.2
Timing: begun
2hr prior to
operation and
continued every
12 hrs. Mean no
of days treatment
8.3 ± 6.4
Additional noncomparative
prophylaxis:
Not reported
Additional noncomparative
prophylaxis:
none
Pre-existing risk
factors: 36%
malignant disease,
30% varicose veins
(numbers distributed
evenly between
study groups)
Length of
follow up
Outcome
measures
Both
groups:
daily from
day 1 postop until
discharge
DVT Confirmed
by: I 125 fibrogen
scanning of both
legs, with positive
venogram
confirmation
Effect size
Comments
HTA report the IPC
vs no prophylaxis. 2
patients excluded
from IPC group as
they had received
oral anticoagulants.
Patients in the
PE
Confirmed Int: 1/28
heparin group were
Control: 1/24
by: Not routinely
treated significantly
p value: 1.000
assessed in all
longer than IPC,
Neither patient had
patients, but
been diagnosed with primarily because
investigated
of discontinuance
DVT
where suspicion
of IPC due to
by chest X-ray,
discomfort. 1
lung scan or
patient from each
pulmonary
study group with a
angiogram
postive FUT test
Bleeding related Int: 9/29
refused venogram.
complications
Control: 14/24
If these patients are
number of patients p value: 0.4424
analysed as having
requiring
DVT the difference
transfusion
between IPC and
heparin is no longer
significant
Int: 6/28
Comparison: 5/24
p value: Not
significant
Not reported:
Proximal DVT,
PTS, QoL,
Bleeding, LoS
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
426 of 648
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Fasting et al,
152
1985
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Intervention
Comparison
Type:
Type: Thigh-length
Unfractionated
graduated
compression stockings heparin Dose:
5000IU
Timing: Begun eve
Timing: Begun
before surgery and
eve pre-surgery
worn for at least five
112
and repeated
randomised Intervention: Mean days and stopped
twice daily for at
when patient mobile
age: 60 yrs (range
15
least 5 days until
excluded (9 39-7) M/F:29/23
mobile. All
Additional nonGCS, 6
patients received
Control: Mean age: comparative
UFH)
a dose 2-3hrs
60 yrs (range 39-80) prophylaxis:
before surgery
Not reported
M/F:20/25
Total: 97
Intervention
: n = 52
Control: n =
45
Type of surgery:
General surgery
under general
anaesthesia and
>1hr
(&
Duration of surgery)
Pre-existing risk
factors: Malignancy,
obesity, previous
DVT or varices
Length of
follow up
Outcome
measures
Both
treatments
were
continued
for at least
five days
after
operation
and were
only
stopped
when
patients
were
mobile.
DVT Confirmed
99m
by:
Tc plasmin
th
test on 5 post-op
day
Int: 3/52
Control: 3/45
p value: Not
significant
Fatal PE
Confirmed by:
Autopsy
Int: 0/52
Control: 1/45
p value: Not
significant
Bleeding related
complications
Plasmin
test
performed
five days
after
surgery.
Major postperative
haemorrhagic
complications:
Not defined
Major post-op
haemorrhagic
complications
Int: 0/52
Control: 0/45
p value: Not
significant
Peroperative
bleeding: Not
defined
Effect size
Peroperative
bleeding (ml)
Int: 505 (50 – 3250)
Control: 554 (50
3500)
p value:
Not significant
Patients
transfused:
Int: 26/52
Control: 29/45
p value: Not
significant
Mean no of
transfusions:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
427 of 648
Comments
Not reported:
PROXIMAL DVT,
PTS, QoL, survival,
LoS, funding
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Length of
follow up
Outcome
measures
Effect size
Int: 1.5 (range 0-9)
Control: 2.3 (range
0-11)
p value: Not
significant
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
428 of 648
Comments
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Francis et al,
162
1992
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total:
Intervention
: n = 98
Control: n =
103
Patients
characteristics
Type of surgery:
Orthapaedic Total
hip replacement
Duration of surgery
not reported
Intervention
Type: bilateral thighcalf IPC Dose: 3555 mm Hg
Timing: applied
immediately prior to
surgery. Continued
Intervention: Mean until venography (6-8
day post-op).
age: 64±12 yrs
M/F:43/55
Additional nonControl: Mean age: comparative
prophylaxis:
64±5 M/F:52/51
bilateral thigh-high
GCS. Patients moved
Pre-existing risk
factors: 13 patients from bed to chair on
(Int 7, control 6 - Not 2nd day post-op,
began ambulation and
significant
difference) had prior physical therapy on
3rd day post-op
history of VTE
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Type: Warfarin
Dose: low
intensity regimen,
adjusted to
achieve INR of 1.5
on day of surgery,
and 2.5 postoperatively
Timing: Begun 10
-14 days preoperatively.
Continued until
venography (6-8
day post-op).
Additional noncomparative
prophylaxis:
bilateral thigh-high
GCS. Patients
moved from bed
to chair on 2nd
day post-op,
began ambulation
and physical
therapy on 3rd
day post-op
429 of 648
Length of
follow up
Intervention
until
venography
(on
average
around day
9)
Outcome
measures
Effect size
Int: 26/98
DVT Confirmed
by: Venography 6- Control: 32/103
p value: 0.5346
8 days post-op.
Bilateral: Int. 87,
control. 84.
Operated-on leg
only: int.11,
control 19
Proximal DVT
Confirmed by:
venography (as
above).
Int: 12/98
Control: 3/103
p value: <0.012
Length of
Hospital Stay
Mean LoS 9 days
(s.d. not reported).
LoS not reported
seperately for each
group
Comments
Comments: Of the
initial 232 patients
randomised, 220
received
prophylaxis (all
assessed for
bleeding/arterial
thrombotic
complications), 201
were assessed for
DVT with
venography.
Overall incidence of
deep calf vein
(distal) thrombi
significantly lower
in IPC group.
Not reported: PE,
Fatal PE, PTS,
QoL:
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Haas et al,
201
1990
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 128
Type of surgery:
Orthapaedic
Unilateral (unilateral or
Intervention bilateral total knee
arthroplasty)
: n = 36
Control: n = Duration of surgery
not reported
36
Bilateral
Intervention
: n = 22
Control: n =
25
Intervention
Comparison
Type: IPC thigh
(Kendall)
Dose: 35 - 55 mm Hg
Type: aspirin
Dose: 650mg 2x
per day
Timing: Applied to
uninvolved leg pre-op
and to involved leg
immediately post-op.
Worn continously.
Removed morning
after post-op V/Q lung
scan
Timing: started
day before
surgery and
continued until
discharge
Intervention:
Unilateral Mean
age: 70.2 yrs (s.d.
not reported)
M/F:11/25
Bilateral Mean age: Additional noncomparative
71.1 yrs (s.d. not
reported) M/F:7/15 prophylaxis:
All patients received
standard physicalControl:
therapy protocol which
Unilateral Mean
included initiation of
age: 67.7 yrs (s.d.
continuous passive
not reported)
motion in the recovery
M/F:10/26
room and walking on
Bilateral Mean age:
the second post-op
69.0 yrs (s.d. not
day
reported)
M/F:12/13
Additional noncomparative
prophylaxis:
All patients
received standard
physical-therapy
protocol which
included initiation
of continuous
passive motion in
the recovery room
and walking on
the second postop day
Control: 57 days
post-op
Int: 5-7
days postop
Outcome
measures
430 of 648
Effect size
DVT Confirmed
by: bilateral
venography 4-6
days post-op
Unilateral:
Int: 8/36
Control: 17/36
p value: < 0.03
Bilateral:
Int: 12/25
Control: 15/22
p value: <0.2
Proximal DVT
Confirmed by:
bilateral
venography 4-6
days post-op
Unilateral
Int: 0/36
Control: 0/36
p value: N/A
Bilateral
Int: 2/25
Control: 1/22
p value: Not
significant
PE
Confirmed
by: V/Q lung scan
5-7 days post-op
(No symptomatic
PE reported in any
patients)
Unilateral
Int: 2/36
Control: 1/36
p value: Not
significant
Bilateral:
Int: 1/25
Control: 0/22
p value: Not
significant
Fatal PE
Pre-existing risk
factors:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
Int: 0
Control: 0
Comments
Comments: 9
patients dropped
out (5 from
intervention, 4
control). Reported
which leg DVT
developed in
(un/involved in
surgery) for
unilateral patients.
Classified thrombus
as small, medium,
large. In unilateral
group no thrombi
developed in
uninvolved leg of
IPC patients (p <
0.01) and
significantly less
large thrombi (p<
0.01)
Not reported: QoL,
PTS, Bleeding,
LoS. Survival
Funding:
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Hansberry et
208
al, 1991
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: n =
74
Patients
characteristics
Intervention
Intervention 1:
External sequential
pneumatic
compression stockings
Int 1: n =
Duration: started
24
during induction of
Interventions &
Int 2: n =
25 Control: control: Age range: anaesthesia and
continued for 48 hours
45 - 75years
n = 25
Type of surgery:
Patients undergoing
total urological
operation
Pre-existing risk
factors: Malignancy,
Anaethesia
>90mins, one
person in Int 2 had a
history of a previous
DVT
Intervention 2:
Thromboembolic
stockings worn preand postoperatively
until full ambulatory.
Comparison
Length of
follow up
Outcome
measures
Type: Heparin
(5000 units) +
dihydroergotamine
mesylate (0.5mg)
every 12 hours.
6 days
postoperati
vely or
discharge if
sooner.
DVT (overall)
Confirmed
by:venography
and In-labelled
platelet scans
Duration: started
2 hours
preoperatively and
continued for 48
hours
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
431 of 648
Int1: 3/24
Int2: 5/25
Control: 2/25
Int 1: 1/24
PE Confirmed
Int 2: 1/25
by:ventillation
perfusion scans, Control: 1/25
platelet
scintigraphy and
lung scan - all
patients here had
DVT
Wound related
complications
Additional noncomparative
prophylaxis:
Not reported
Effect size
Int 1: 2/24
Int 2:2/25
Control: 1/25
Comments
The paper did not
report any
dropouts
Not reported:PTS,
Fatal PE, QoL,
Survival
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Kaempffe et
267
al, 1991
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total:
149
Int: 48
Cont: 52
49 patients
excluded
after
ransomisati
on:
Protocol
broken: 24
Surgery
cancelled:
14
Refused to
participate:
8
Death: 3
Patients
characteristics
Type of surgery:
Elective total hip or
knee replacement
Intervention
Intermittent pneumatic
compression (Kendall)
(calf and thigh
segments)
Intervention
average age
(range): 60 (40-80)
years; M/F 47/1
Timing:
Started at surgery, not
stated when stopped.
Control
average age
(range): 45 (18-77)
years; M/F 51/1
Additional noncomparative
prophylaxis:
none reported
Pre-existing risk
factors:
Average number 2.4
(0 to 6)
Previous DVT/PE,
varicose veins, heart
disease, obesity,
hypertension,
malignancy,
smoking history,
previous
cerebrovascular
accident or
diabetes).
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Length of
follow up
Coumadin: 10mg Not stated
the evening before
surgery, 5mg the
evening of
surgery, then dose
adjusted to
maintain the
prothrombin time
level at 15
seconds with a
control of 11 to 12
seconds.
Timing:
Started evening
before surgery,
not stated when
stopped
Outcome
measures
Effect size
DVT Confirmed by Int: 12/48
venography*
Control: 13/52
p value: 1.0000
Proximal DVT
Confirmed by
venography*
Mortality
Int: 8/48
Control: 6/52
p value: 0.5681
Int: 1/48
Control: 2/52
p value: 1.0000
Additional noncomparative
prophylaxis:
none reported
*Venography
performed on
operated leg only.
Other leg scanned
if operated leg had
a positive scan.
Performed on
average at
postoperative day
10
2 deaths (1 in each
group) suspected
as a result of PE.
Not confirmed by
autopsy.
Not reported:
PE, LoS, QoL, PTS
Funding:
not reported
Average (range)
number of units
of packed red
blood cells
transfused per
patient during
the perioperative
period
432 of 648
Comments
Int: 1.4 (0 to 6)
Control: 2.0 (0 to 6)
p value: not
reported
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Study
Type
Killewich et al, RCT
290
2002
Evidenc
e level
1+
No. of
patients
Total :45
Int1: 13
Int2: 15
Cont: 16
Patients
characteristics
Patients undergoing
major abdominal
surgery (35 bowel &
10 aortic
reconstructions).
Intervention
Intervention 1:
IPCD (thigh-length) +
Heparin (5000 units)
subcutaneously twice
a day
Comparison
Heparin (5000
units)
subcutaneously
twice a day
Intervention 2:
Mean age:67
IPCD (thigh-length)
Gender ratio
(M/F):44:1 (98%:2%) during surgery and for
the first 48 hrs after.
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
5 days or
until day of
discharge
Outcome
measures
Effect size
Int 1: 0/13
Proximal DVT
Int 2: 0/15
Confirmed by
venous duplex US Control: 0/16
scan
Comments
It appears that the
treatment was
different to pts with
aortic
reconstructions.DV
T prophylaxis was
initiated in the
operating room
after induction of
anesthesia and
continued until post
op day 5 or
discharge
Not reported:
PE, PTS, Bleeding
related
complications, QoL,
Survival
433 of 648
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Kosir et al,
299
1998
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total :136
Int: n = 68
Cont: n =
68
Patients
characteristics
Patients for general
surgeries lasting at
least 1 hr and
general or spinal
anesthesia.
Intervention
Sequential pneumatic
compression devices
applied before
induction of anesthesia
and for 48 hrs post-op.
Intervention:
MeanAge:62.4
Control:
MeanAge:62.5
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Unfractionated
heparin (5000
units)
subcutaneously
every 12 hrs
starting 1 hr
before surgery
until 48 hrs
postop.
434 of 648
Length of
follow up
30 days
Outcome
measures
Effect size
DVT Confirmed
by Duplex venous
studies of the
lower extremities
Int: 1/68
Cont: 1/68
p value: not
significant
PE Confirmed by
Duplex venous
studies of the
lower extremities
Int: 1/68
Cont: 1/68
p value: not
significant
Fatal PE:
Confirmed by not
stated
Int: 0/68
Cont: 1/68
p value: not
significant
Survival:
10 deaths within 30
days, one due to PE.
Not stated from
which groups.
Comments
Mortality not clearly
explained
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Maxwell et al,
349
2001
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 228
Type of surgery:
"Major" procedure
Interventio for gynaecological
n: n = 106 malignancy
Control: n
Intervention:
= 105
Median age: 62 (3585) yrs Gender not
reported Mean
duration of surgery:
not reported
Control: Median
age: 60 (41-87)
years Gender not
reported Mean
duration of surgery:
not reported
Intervention
Comparison
Type: Low
molecular weight
heparin
(Dalteparin)
Dose: 2500 units
Timing: Started with
induction of anesthesia subcutaneously 1and continued for first 2 hours before
5 days postoperatively. surgery and 2500
Device stopped when units 12 hours
after first dose.
patient was walking
Then from
and restarted when
postoperative day
back in bed.
1 5000 units per
day up to post
Additional nonoperative day 5. If
comparative
the patient was
prophylaxis:
confined to bed
Not reported
after day 5,
continued
prophylaxis until
day of discharge
or ambulatory.
Type: External
pneumatic
compression sleeves
Length of
follow up
Outcome
measures
Control: 5
days
DVT Confirmed
by: real-time US
compression
technique with
duplex and colour
Doppler imaging.
Int: 1/106
Control: 2/105
p value: 0.6214
Proximal DVT
Confirmed by:
Doppler flow US
at postoperative
day 3
Int: 1/106
Control: 2/105
p value: 0.6214
PE
Int: 0/106
Control: 0/105
p value: N/A
Bleeding related
complications
Median external
blood loss: Int:
350mL Control:
350mL
p value: 0.81
Int: 5 days
(patients
also
telephoned
30 days
postoperati
vely and
questioned
for signs
and
symptoms
of delayed
VTE)
Effect size
Thrombocytopen Int: 4/106
ia
Control: 2/105
p value: 0.68
Comments
Comments:
Screened everyone
for DVTs, only
reported proximal.
Outcomes
measured at
postoperative days
3 to 5, only followed
up by telephone
call 30 days after
surgery. Trial
designed to detect
differences in
complications.
Discrepancy with
randomisation:
claimed to have
carried out an
intention to treat
analysis but 17
patients that were
randomised were
not included in
results. These
patients dropped
out for various
reasons, not stated
to which group they
were randomised.
Funding: not
reported
Not reported:
All DVTs, PE,
postthrombotic leg,
QoL, survival,
length of hospital
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
435 of 648
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Length of
follow up
Outcome
measures
Effect size
Comments
stay
Also reported:
number of
transfusions,
wound separation,
ecchymosis,
hematoma - none
significant
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
436 of 648
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
McKenna et
355
al, 1980
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 46
Patients
characteristics
Type of surgery:
Elective total knee
replacement
IPCD: 10
Placebo: 12
Low dose
Intervention:
aspirin: 9
Gender M/F: 3/7
High dose
aspirin: 12
Controls:
2 low dose Low dose aspirin:
and 1 high Gender M/F: 0/9
High dose aspirin:
dose
Gender M/F: 1/11
aspirin
participants Placebo: 3/9
were
Pre-existing risk
excluded
factors:
from the
none reported
analysis
because
valuation
incomplete
or aspirin
administere
d
incorrectly
Intervention
Comparison
Type:
IPCD
thigh and calf cuffs
Type:
Aspirin low dose:
325mg 3x per day
Timing:
started at beginning of
surgery for unoperated
leg and at the end of
surgery for operated
leg. Both continued
until discharge
Aspirin high dose:
1300mg 3x per
day
Additional noncomparative
prophylaxis:
none reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Timing:
started
immediately after
admission and
continued until
discharge
Additional noncomparative
prophylaxis:
none reported
437 of 648
Length of
follow up
Studied
until
discharge.
Median
hospital
stay after
operation
was 16
days
Outcome
measures
DVT Confirmed
by phlebography
or fibrinogen test
Effect size
IPCD: 1/10
Low dose aspirin:
7/9
p value: <0.005
Comments
Comments:
High dose aspirin:
1/12 Not significant
Proximal DVT
Confirmed by
phlebography or
fibrinogen test
IPCD: 0/10
Low dose aspirin:
3/9
High dose aspirin:
0/12
p value: not
reported
PE
Confirmed
by V/Q lung scan
IPCD: 1/10
Low dose aspirin:
2/9
High dose aspirin:
1/12
p values not
reported
Major Bleeds
IPCD: 0/10
Low dose aspirin:
0/9
High dose aspirin:
1/12
p values not
reported
Mortality
IPCD: 0/10
Low dose aspirin:
0/9
High dose aspirin:
0/12
p values not
reported
Not reported:
QoL, postthrombotic
syndrome, LoS
Funding
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Mellbring and
Palmer,
359
1986
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 114
Intervention
: n = 54
Control: n =
54
Type of surgery:
Major abdominal
(cholecystectomy or
more advanced)
Intervention
Type: calf-length IPC
Dose: up to 40 mm
Hg
Comparison
Length of
follow up
Both
Type:
Dihydroergotamin groups: 9
days
e + LDUH
Dose: 0.5 mg +
5000 IU
Timing: from
anaesthetic until end of
Timing: Begun
surgery
2hrs pre-surgery
and continued
2x/day until
Additional nonpatient fully
Intervention: Mean comparative
mobilised
prophylaxis:
age: 67.8±7.8 yrs
Thigh-length GCS
M/F:22/32
Additional nonapplied to one leg
comparative
Control: Mean age: (allocated randomly)
prophylaxis: Not
64.2±7.8 M/F:29/25
reported
Median operating
time: Int: 135 min
(25 - 420) Control:
48 min (45 - 360)
Pre-existing risk
factors: Not
reported
Outcome
measures
Effect size
Comments
Comments: 6
patients excluded
(4 intervention, 2
control). Both
patients excluded
from contol due to
post-operative
bleeding requiring
re-operation and
dextran
Bleeding related Int: mean 580,
administration. All
med 300, range
complications
patients
minor - 3900
perioperative
Control: mean 690, randomised to
bleeding (ml)
receive stocking on
med 450, range
calculated from:
one leg. Subgroup
amount of blood in minor - 2800
analysis (heparin
suction draingage; p value: Not
group only, or IPC
significant
and estimated
group only) to
content of blood in
consider adjuvant
swabs
effect of GCS not
Survival (specify) Int: 54/54
possible as results
Control: 54/54
not amenable to
p value: Not
analysis. Incidence
significant
of thrombosis did
not differ
significantly
between stockinged
and non-stockinged
leg.
Int: 10/54
DVT Confirmed
Control: 2/54
by: I 125 FUT,
started pre-op and p value: <0.05 (
then on days
1,3,5,7,9 post-op
(daily if a positive
reading found). Or
until discharge if <
9 days
Not reported:
Proximal DVT, PE,
QoL, LoS, PTS
Funding:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
438 of 648
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Norgren et al,
387
1998
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: n =
40
Patients
characteristics
Type of surgery:
Patients sheduled
for elective knee
Interventio replacement. Overall
M/F: 13/27
n: n = 21
Control: n Mean age: 72years
Intervention
= 19
M/F: 4/11
11 patients
Control
dropped
M/F: 7/7
out so
results
based on
29 patients:
Int:15 &
cont:14
Intervention
Type: foot pump
(ActOne) mechanical
compression
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Type: LMWH
Additional noncomparative
prophylaxis:
Not reported
Length of
follow up
Control:
3mths
Int: 3mths
Outcome
measures
Effect size
DVT (overall)
Confirmed by:
venography
performed on day
7-10.
Int: 4/15
Control: 0/14
p value: <0.05
Fatal PE
Confirmed by
autopsy:
Int: 1/15
Control: 0/14
p value: Not
significant
Comments
Comments: 11
patients dropped
out from the study,
5 in the LMWH
group and 6 in the
foot pump group
There were no
signs of proximal
thrombosis
Not reported:
PTS, Bleeding
related
complications, QoL,
Survival
439 of 648
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Paiement et
400
al, 1987
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Intervention
Comparison
Length of
follow up
10 days
Type: Warfarin
(low-dose)
Dose: 10 mg
pre-op, 5 mg postop, thereafter
Timing: Started eve
before operation. Worn adjusted to
Interventio
maintain PTT at
Intervention: Mean continously
n:
15 secs for control
age: Not reported
n = 66
at 11 - 12 secs
Additional nonM/F:70/68 in the
(17 left
comparative
study.
study)
Timing: Started
prophylaxis:
Control:
eve before
Control: Mean age: Not reported
n = 72 (8
operation,
Not reported
left study)
discontinued 2
M/F:70/68 in the
days post
study.
phlebography if
negative resul
Total: 165
(138
completed
study)
Type of surgery:
Total hip
replacement
Duration of surgery
not reported
Type: Bilateral thighlength IPC device
Dose: 45-55 mmHg
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
440 of 648
Outcome
measures
Effect size
DVT Confirmed
by: Venography
10th day post-op.
Performed on
operated limb first.
If negative,
contralateral limb
also assessed
Int: 11/66
Control: 12/72
p value: Not
significant
Proximal DVT
Confirmed by:
Venography
Int: 9/66
Control: 4/72
p value: < 0.057
PE Not routinely
screened for.
Symptomatic PE
investigated by
V/Q and
angiogram if high
probability
Int: 0
ontrol: 0
p value: not
reported
Bleeding related
complications
Major bleeding
(overt and
associated with
decrease in
haemoglobin level
of ≥ 2g/dl;
required
transfusion of 2 or
more units;
retroperitoneal or
occurred in major
prosthetic joint;
intracranial);
Intraoperative and
post-operative
Major bleeding:
Int: 0/66
Control: 0/72
p value: N/A
Overall blood loss
for primary
procedures: Int:
1821 ± 721 ml
Control: 1861 ±
648 ml Not
significant
Revision cases
Int: 3122 ± 1700 ml
Control: 3218 ±
2076 ml Not
significant
Comments
Comments:
Patients strafied by
sex and previous
history of VTE prior
to randomisation. 4
of 17 patients who
withdrew from IPC
group did so due to
intolerance of IPC
device. None of
DVTs occurred in
patients with
previous history of
VTE
Not reported:
PTS, LoS, QoL,
Survival, Funding
info
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Length of
follow up
Outcome
measures
blood loss (weight
of sponges;
suction drainage
blood loss;
estimates of blood
on wound drapes)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
441 of 648
Effect size
Comments
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Pitto et al,
407
2004
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 216
Type of surgery:
Total hip
Interventio replacement in
n: n = 100 patients with
Control: n osteoarthritis
= 100
Intervention:
Mean age: 57.3±12
yrs M/F:30/70
Mean duration of
surgery: 69+10
minutes
Control:
Mean age: 58.1±11
M/F:32/68
Mean duration of
surgery: 65+11
minutes
Intervention
Comparison
Type: A-V Impulse
System foot pump
(slippers) and patient
in Trendelenburg
position (head-high,
feet-low)
Type: Low
molecular weight
heparin
(Fraxiparin)
continued after
surgery
Cycle: 130 mmHg for
one second every 20
seconds
Dose: adjusted
to body weight,
0.2 to 0.6ml; 0.1ml
= 950IU of anti
Xa.
Timing: (duration)
started after surgery,
not stated when
stopped - could be
used until discharge
Additional noncomparative
prophylaxis: Bilateral
thigh-high antithromboembolic
stockings.
Physiotherapy and
mobilisation with
partial weight bearing
usually started on
postoperative day 2.
Low molecular weight
heparin (Fraxiparin)
administered
subcutaneously 12
hours preoperatively
(dose adjusted to body
weight, 0.2 to 0.6ml;
0.1ml = 950IU of anti
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Timing: started
postoperatively,
not stated when
stopped but could
be until discharge.
Additional noncomparative
prophylaxis:
Bilateral thigh-high
antithromboembolic
stockings.
Physiotherapy and
mobilisation with
partial weight
bearing usually
started on
postoperative day
2. Low molecular
weight heparin
(Fraxiparin)
administered
442 of 648
Length of
follow up
Outcome
measures
Control: 45 DVT Confirmed
days
by: serial bilateral
duplex
Int: 45
Proximal DVT
days
Confirmed by:
serial bilateral
duplex
Distal DVT
Confirmed by:
serial bilateral
duplex
Effect size
Int: 3/97
Control: 6/94
p value: <0.05
Int: 0/97
Control: 2/94
p value: <0.05
Int: 3/97
Control: 4/94
p value: <0.11
Not significant
Int: 1/100
Symptomatic
Control: 1/100
DVT Confirmed
by: serial bilateral Not significant
duplex
PE
by:
Confirmed
Int: 0/100
Control: 0/100
Fatal PE
Confirmed by:
Int: 0/100
Control: 0/100
Major bleeding
from wound
Int: 0/100
Control: 0/100
Major bleeding
not related to
wound
Int: 0/100
Control: 0/100
Heparin-induced Int: 0/100
thrombocytopeni Control: 1/100
p value not reported
a
QoL - no. hips
with no bruising
at day 3
Int: 59
Control: 42
p value: <0.05
QoL - no. hips
with no bruising
at day 10
Int: 78
Control: 50
p value: <0.05
Comments
Comments:
Discrepancy with
randomisation:
computer
generated numbers
lead to 100 in each
group but 216 were
randomised. 16
dopped out of
mechanical group
because did not
tolerate foot pump.
Dropouts occurred
between
postoperative days
3 and 10.
Not reported:
PE, LoS,
postthrombotic leg
Also repoted:
Distal DVT, minor
bleeding from
wound
DVT detection at
day 3: Int 2 Cont: 4,
DVT detection at
day 10 Int: 1 Cont:
2)
Funding: stated
that authors have
or will receive
benefits from a
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Xa).
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
subcutaneously
12 hours
preoperatively
(dose adjusted to
body weight, 0.2
to 0.6ml; 0.1ml =
950IU of anti Xa).
443 of 648
Length of
follow up
Outcome
measures
Effect size
QoL - no. hips
Int: 40 Control:
with no oozing at 23 p value: <0.05
day 3:
QoL - no. hips
Int: 95
with no oozing at Control: 75
day 10
p value: <0.05
Survival
Int: 100/100
Control: 100/100
Comments
commercial party
directly related to
the subject of this
study. Does not
state who the
commercial party is
nor what the
benefits are.
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Study
Type
Rasmussen et RCT
422
al, 1988
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 249
in study,
159 in this
comparison
Type of surgery:
Major abdominal
(included urological
and gynaelogical
patients)
Intervention
: n = 74
Control: n =
85
Duration of
surgery: mean int:
2.75 hrs control: 2.5
hrs
Intervention
Comparison
Type: Bilateral kneehigh GCS
Type: LDUH
Dose: 5000 IU
Timing: from evening
prior to operation until
complete mobilisation,
or for not less than five
days post-op
Timing: every 12
hours from
evening prior to
operation until
complete
mobilisation, or for
not less than five
days post-op
Additional noncomparative
Intervention: Mean prophylaxis:
none reported
age: 63 yrs (range
41-87) M/F:33/41
Control: Mean age:
62 yrs (range 40-90)
M/F:40/45
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Additional noncomparative
prophylaxis:
none reported
Length of
follow up
Both
groups:
until
discharge
Outcome
measures
Effect size
DVT Confirmed
by: 99m Tclabeled plasmin
test on 4/5 post-op
day
Int:
22/74
Control: 25/85
p value: Not
significant
PE
Confirmed
by: Not routinely
screened for.
Int: 0
Control: 0
p value: None
were clinically
diagnosed during
the study
Survival
Int: 74/74
Control: 85/85
p value: Not
significant
Comments
Comments: HTA
report GCS +
LDUH vs LDUH
comparison. 1
patient excluded
after randomisation.
Paper does not
report from which
group. No DVTs
systematic.
Not reported:
Proximal DVT,
PTS, Bleeding,
QoL, LoS
Funding:
plasmin test
provided by Novo
Ltd and Novo
diagnostics
444 of 648
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Rokito et al,
432
1996
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total:
110
Patients
characteristics
Type of surgery:
Reconstructive
spinal surgery
Intervention
Pneumatic
compression boots
Int: 35
Cont: 33
Timing:
Intervention
Average age (range) Started at surgery and
continued until duplex
44 (22-70) years
Also 42
dopplers were
patients
obtained.
randomised Control
average age 45 (18to a TED
Mean + SD duration of
77) years
stocking
only group.
surgery: 286 +127
Results for
mins
Pre-existing risk
this group
(range: 97-750 mins)
factors:
are not
none reported
presented
Additional nonhere.
comparative
prophylaxis:
Thigh high TED
stockings
Comparison
Coumadin: 10mg
the evening before
surgery the dose
adjusted to
maintain the
prothrombin time
level at 1.3 to 1.5
times the control.
Timing:
Started evening
before surgery
and continued
until duplex
dopplers were
obtained.
Mean + SD
duration of
surgery: 232 +89
mins
(range: 95-575
mins)
Additional noncomparative
prophylaxis:
Thigh high TED
stockings
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
445 of 648
Length of
follow up
Outcome
measures
Intervention DVT Confirmed by
carried out duplex doppler
until duplex
doppler
scan.
Average of PE (symptomatic)
5.3 days
Patients
followed for Mean + SD
(range)
1 year
intraoperative
blood loss
Effect size
Int: 0/35
Control: 0/33
p value: not
significant
Int: 0/35
Control: 0/33
p value: not
significant
Int: 783 +631 (1002800) ml
Control: 930 +443
(200-2250) ml
p value: (not
reported)
Comments
Not reported:
proximal DVT, LoS,
QoL, PTS, survival
Funding:
TED stockings and
pneumatic
compression boots
provided by Kendall
Healthcare
Products
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Santori et al,
450
1994
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: n =
132
Intervention
: n = 67
Control: n =
65
Type of surgery:
Patients undergoing
total hip
replacement. All
patients had
compression
stockings after
operation
Intervention
Intermetent plantar
foot pump (aka
impulse group) on both
feet immediately after
the operation and used
for 7 to 10 days. When
patients started
walking at
postoperative day 4 or
5 the foot pump was
only used when the
patient was in bed.
Comparison
Intervention
for 8 to 10
5000 Units 3x per days,
follow-up 6
day for 10 days
starting on the day weeks
before the
operation
Calcium heparin.
Additional
Excluded:
prophylaxis:
history of VTE,
Graduated
varicose veins,
compression
venous
stockings on both
insufficiencey in the Additional
legs after
prophylaxis:
legs, malignant
operation. Neither
Graduated
neoplasm
the length nor for
compression stockings how long they
Intervention: Mean on both legs after
were worn was
operation. Neither the stated.
age: 72.4±6.65
length nor for how long
M/F:19/48
Control Mean age: they were worn was
Physiotherapy
stated.
69.8±6.22
with mobilisation
started on 2nd
M/F:15/50
Physiotherapy with
postoperative day.
mobilisation started on Walking began on
Pre-existing risk
nd
2 postoperative day. 4th or 5th
factors: Not
th
reported
Walking began on 4
postoperative day
th
or 5 postoperative
day
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
446 of 648
Outcome
measures
DVT (overall)
Confirmed
by:thermography
and doppler US
followed by
phlebography
Effect size
Int: 9/67
Control: 23/65
p value: <0.005
"Major" proximal Int: 2/67
DVTs
Control: 11/65
p value: : 0.0083
"Major" proximal Int: 0/67
& distal DVTs
Control: 2/65
p value: : 0.2406
Mean +SD total
blood loss (ml)
Int: 490 +195.27 (n
= 67)
Control: 520
+189.16 (n = 65)
P value: not
reported
Mean +SD
volume of blood
transfused (ml)
Int: 308 +289.15 (n
= 67)
Control: 300 +267.7
(n = 65)
P value: not
reported
Comments
The paper did not
report any dropouts
2 PEs (1 fatal) in
the heparin group
but not stated how
confirmed
Not reported:PTS,
PE, QoL, Survival
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Smith et al,
473
1978
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
7 Surgical
units
consisiting
of 305
patients.
Only 2
groups will
be inlcuded
in this
analysis,
therefore
Int:n = 96
Control:n =
99
Patients
characteristics
Patients aged over
>40 admitted for an
operation likely to
last more than
30minutes. Mean
age 60±12yrs(SD)
Intervention
Intermetent pneumatic
calf compression (also
referred to as calf
pumps)
Additional noncomparative
Intervention: n = 96 prophylaxis:
Not reported
M/F: 7/7
Control: n = 99
M/F: 4/11
Pre-existing risk
factors:
malignancy without
DVT Int: n = 11,
control: n = 19
malignancy with
DVT Int: n = 9,
control: n = 9
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Length of
follow up
500ml Dextran 70 7 days or
until
in saline over at
discharge
least 30 minutes
beginning with the
induction of
anaesthesia. A
further 500ml
given over 4 hours
within 8 hours of
completing the
operation
Additional noncomparative
prophylaxis:
Not reported
447 of 648
Outcome
measures
Effect size
Int: 36/95 Control:
DVT (overall)
21/97
confirmed byIp value: <0.05 *
fibrinigen uptake
test and leg scans
Bleeding
Complication
Bleeding
Complication
Int: 2/96
Control: 17/99
p value: <0.01
Comments
There were 3
treatment
regimens, however
only the
comparisons not
inlcuded in the HTA
report were
recorded. 12
people were
excluded from the
trial
*In three of the
patients the
scanning was
considered
unsatisfactory.
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Study
Type
Stannard et al, RCT
482
1996
Evidenc
e level
+
No. of
patients
Total: 75
Int 1: 25
Int 2: 25
Control: 25
Patients
characteristics
Intervention
Intervention 1:
Type of surgery:
uncemented total hip Type: Bilateral Foot
pump + LDUH +
arthroplasty
aspirin
Dose: FP 16hrs/day
Duration of
for first 3 days, then
surgery:
Int1:
mean 106 (85 - 128) 12hrs/day; LDUH
5000U; Aspirin 325 mg
mins; Int2: mean
113 (15 - 135) mins;
Cont: mean 111 (87 Intervention 2:
Type: Bilateral Foot
- 140) mins;
pump 16hrs/day for
first 3 days, then
Intervention 1:
12hrs/day
Mean age: 68.7
(range 48-86) yrs
Timing:
M/F:not reported
FP begun immediately
Intervention 2:
Mean age: 65 (range post-surgery and
51-79) yrs M/F:not continued until end of
study; LDUH begun
reported
12hrs pre surgery and
Control:
every 12hrs for first 3
Mean age: 69.7
days post-surgery,
(range 28-86) yrs
then aspirin 3x daily
M/F:not reported
until end of study
Comparison
Type: LDUH +
aspirin
Dose: LDUH
5000U; Aspirin
325 mg
Timing:
LDUH begun
12hrs pre surgery
and every 12hrs
for first 3 days
post-surgery, then
aspirin 3x daily
until end of study
Additional
prophylaxis:
Spinal
anaesthesia:
21/25
Additional
prophylaxis:
Spinal anaesthesia:
22/25
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
448 of 648
Length of
follow up
2 weeks
postoperati
vely
Outcome
measures
Effect size
DVT Confirmed
by: Duplex US.
Positive scans
confirmed by
venography
Int1: 0/25
Int2: 0/25
Cont: 5/25
p value: = 0.009
PE
Confirmed
by: Not routinely
screened for. No
confirmatory tests
reported
Int1: 0/25
Int2: 0/25
Control: 1/25
p value: Not
reported
Bleeding related
complications
Surgical wound
drainage - time
taken for wound to
seal (no of days
post-op)
Int1: 5.9
Int2: 3.8
Control: 6.2
p value: = 0.05
Survival (specify)
Int1: 25/25
Int2: 25/25
Control: 25/25
p value: Not
significant
Comments
3/5 DVTs were
symptomatic. 1 PE
was symptomatic.
4/5 patients who
developed DVT had
spinal anaesthesia.
Two patients
reported as
excluded from
study due to
abnormal pre-op
US findings. Does
not report to which
group(s) they
belonged
Not reported:
LoS, QoL,
postthrombotic leg,
proximal DVT
Funding: Not
reported
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Warwick et al,
536
1998
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: n =
290
Patients
characteristics
Intervention
foot pump for 7days
Type of surgery:
Patients undergoing
total hip replacement
Interventio Intervention: Mean
n: n = 147 age: 68±11
Control: n M/F:94/53
= 143
Pre-existing risk
factors:
Previous
thomboembolism:
Int: n = 2, control:n =
3
Comparison
Enoxaparin
Dose: 40mg/dly
for 7 days
Length of
follow up
Control:
3mths
Int: 3mths
Outcome
measures
DVT (overall)
Confirmed
by:venography on
6th, 7th & 8th day
Int: 24/136
Control: 18/138
(95%CI, -3.9 to
+13.0%)
p value: Not
significant
Proximal vein
thrombosis
Int: 17/136
Control: 12/138
(95%CI, -3.5 to
+11.1%)
p value: Not
significant
Timing: 7days
Additional
prophylaxis:
Not reported
Effect size
Distal vein
thrombosis
Int: 7/136
Control: 6/138
(95%CI, -4.2 to
+5.8%)
p value: Not
significant
Symptomatic PE
Confirmed by
ventilation
perfusion
scanning
Int: 1/136
Control: 0/138
p value: Not
significant
Fatal PE
Confirmed by:
Int: 0/136
Control: 0/138
p value: Not
significant
Int: 1/136
Readmission to
hospital because Control: 1/138
p value: Not
of DVT:
significant
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
449 of 648
Comments
Comments: 136
patients in the
interveniton and
138 in the
comparison group
completed both
venography and the
3 month follow-up
No patient died
during follow-up
Not reported:
PTS, Bleeding
related
complications, QoL,
Survival
Also reported:
Intraoperative blood
loss, postop
drainage, median
no. of units
transfused, oozing
and bruising of
thigh
DRAFT FOR CONSULTATION
Mechanical vs Pharmacological prophylaxis
Bibliographic
reference
Warwick et al,
537
2002
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Total: 229
Intervention
: n = 117
Control: n =
112
Type of surgery:
Patients undergoing
total knee
replacement(TKR).
All patients had
stockings fitted
below the knee
before surgery
Intervention
A- V impulse foot
pump
Comparison
Enoxaparin LMWH
Additional noncomparative
prophylaxis:
Not reported
Intervention: Mean
age:73±9
M/F:43/74
Control: Mean age:
71±10 M/F:37/75
Pre-existing risk
factors:
Previous
thomboembolism:
Int: n = 7, control:n =
4, Smoking, varicose
veins
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
450 of 648
Length of
follow up
3 months
Outcome
measures
Effect size
DVT (overall)
Confirmed by:
Ascending
venography on 6th
& 8th day
Analysis based on
nos of pateints who
completed
venography
Int: 57/99
Control: 48/89
p value: Not
significant
Proximal vein
thrombosis
Int: 4/99
Control: 0/89
p value: Not
significant
Fatal PE
Confirmed by:
Int: 2/99
Control: 0/89
p value: Not
significant
Bleeding related
complications
Int: 0/99
Control: 4/89
p value: Not
significant
Comments
Study concluded
that there neither
method provided
superior
prophylaxis. All
patient completed
follow-up but only
99 in the
intervention and 89
in the control were
available for
venography
4 patients were
said to have PE but
paper did not state
which groups they
belonged
Not reported: PTS,
QoL, Survival
DRAFT FOR CONSULTATION
Evidence Table 59: Patient views on mechanical vs pharmocological
Bibliographic
reference
Maxwell et al,
349
2001
Study
Type
Evidenc
e level
Question 3
naire of
views
and
concorda
nce
carried
on
participa
nts of
RCT
No. of
patients
Total: 228
Patients
characteristics
Type of surgery:
"Major" procedure
Interventio for gynaecological
n: n = 104 malignancy
Control: n
Intervention:
= 103
Median age: 62 (3585) yrs Gender not
Not all
patients in reported Mean
duration of surgery:
trial were
not reported
lost to
follow up or
Control: Median
incapable
age: 60 (41-87)
of
participatin years Gender not
reported Mean
g in
postoperati duration of surgery:
ve survey. not reported
Intervention
Comparison
Type: Low
molecular weight
heparin
(Dalteparin)
Dose: 2500 units
Timing: Started with
induction of anesthesia subcutaneously 1and continued for first 2 hours before
5 days postoperatively. surgery and 2500
Device stopped when units 12 hours
after first dose.
patient was walking
Then from
and restarted when
postoperative day
back in bed.
1 5000 units per
day up to post
Additional nonoperative day 5. If
comparative
the patient was
prophylaxis:
confined to bed
Not reported
after day 5,
continued
prophylaxis until
day of discharge
or ambulatory.
Type: External
pneumatic
compression sleeves
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
451 of 648
Length of
follow up
Outcome
measures
Effect size
Control: 5
days
Overall
comfort/pain
Int: 26%
Cont: 4%
Int: 5 days
Suboptimal
performance or
administration of
prophylaxis
Int: 10/104
Cont: 6/103
p value: not
significant
Postoperative
preference for
the intervention
used
Int: 74%
Cont: 78%
Postoperative
preference for
other
intervention
Int: 3
Cont: 4%
(patients
also
telephoned
30 days
postoperati
vely and
questioned
for signs
and
symptoms
of delayed
VTE)
Comments
Comments:
Screened everyone
for DVTs, only
reported proximal.
Trial designed to
detect differences
in complications.
Funding:not
reported
Also reported:
No significant
difference in
proximal DVTs,
median external
bleeding loss,
thrombocytopenia.
Not reported:
All DVTs, PE,
postthrombotic leg,
QoL, survival,
length of hospital
stay
DRAFT FOR CONSULTATION
Evidence Table 60: Regional vs general anaesthesia
Bibliographic
reference
Study
Type
Evidenc
e level
Roderick et al, Systemat 1+
2005
ic Review
11 RCT
75,123,124,
studies
168,227,228,262,356,3
67,431,552
No. of
patients
Patients
characteristics
Total: 939
Int:367
Cont: 384
Type of surgery:
General (1 study)
Urinology (1 study)
Orthopaedc (9
studies)
Misc: 188
(not
reported
number in
each arm)
Intervention
Comparison
Regional
Anaesthesia
General
Anaesthesia
Timing: Ranged from
73 mins to 3 days
Timing: Ranged
from 79 – 150
mins.
Not addressed in 4
studies
Not addressed in
6 studies.
Additional noncomparative
prophylaxis:
LMWH + GCS (one
study);
GCS (two studies);
Dextran 70 (one
study);
Dextran 40 + 7500 IU
H (one study);
ASA, GCS on no-op
limb (one study).
Additional noncomparative
prophylaxis:
LMWH + GCS
(one study);
GCS (two
studies);
Dextran 70 (one
study);
Dextran 40 + 7500
IU H (one study);
ASA, GCS on noop limb (one
study).
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
452 of 648
Length of
follow up
Outcome
measures
Between 4
to 14 days
postoperati
vely
DVT confirmed by
venograph or
fibrinogen uptake
Int : 130/417
Cont: 198/416
p value: 0.0000
PE confirmed by
scan
Int : 21/281
Cont: 32/264
(reported in 6
studies)
p value: 0.0672
Major bleeds
Int : 0/317
Cont: 5/315
(reported in 7
studies)
p value: 0.0243
Proximal DVTs
Int : 14/268
Cont: 47/253
(reported in 6
studies)
p value: 0.0000
Effect size
Comments
Not reported: LoS,
QoL and PTS.
DRAFT FOR CONSULTATION
Regional vs general anaesthesia
Bibliographic
reference
Mitchell et al,
366
1991
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 72
Intervention
: n = 34
Control: n =
38
Patients
characteristics
Type of surgery:
total knee
arthroplasty
Duration of
surgery:
Intervention : mean
122 min Control:
mean 121 min
Intervention
Type: Epidural
anaesthesia Dose:
Timing: Operative
period
Additional noncomparative
Both study groups: prophylaxis: Males
received 650mg
Mean age: 64
aspirin beginning eve
(range38-84) yrs
pre-surgery, females
M/F:45/27
received adjusted dose
No between-group
warfarin PTT 15-16
differences for age
secs. All patients CPM
or sex
machine daily and
physical therapy
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Type: General
anaesthesia
Dose: sodium
theopental
Timing: Operative
period
Additional noncomparative
prophylaxis:
Males received
650mg aspirin
beginning eve presurgery, females
received adjusted
dose warfarin PTT
15-16 secs. All
patients CPM
machine daily and
physical therapy
453 of 648
Length of
follow up
Scan
performed
up to day 8
after
surgery
Outcome
measures
Effect size
DVT Confirmed
by: bilateral
venography 6,7
th
and 8 post-op
days
Int: 12/34
Control: 10/38
p value: Not
significant
All asymtomatic
Proximal DVT
Confirmed by:
Incidence of
Proximal DVT
reported to be 46%
in epidural and 63%
in general
anaesthesia groups.
(actual numbers
can’t be reliably
calculated from
these figures)
PE
Confirmed
by: V/Q scan on
th
6,7 and 8 postop days
10% of patients
reported as having
positive V/Q scan,
all unsymptomatic.
No information on
group.
Length of
Hospital Stay
Int: Mean 10.4 days
Control: Mean 11.0
days
p value: not
reported
Comments
Comments: Male
patients received
aspirin, female
warfarin. No
differences in sex
between study
groups, and
incidence and
distribution of DVT
not affected by
pharmacological
prophylaxis.
Not reported: PTS,
bleeding, QoL,
survival, funding
DRAFT FOR CONSULTATION
Regional vs general anaesthesia
Bibliographic
reference
Modig et al,
368
1981
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 30
Intervention
: n = 15
Control: n =
15
Type of surgery:
Total hip
replacement (for
severe
osteoarthritis)
Duration of
surgery:
Intervention:
147±27.9min
Control: 161.3±34.5
min
Intervention
Comparison
Type: Continuous
lumbar epidural block
Dose: 0.5%
bupivacaine with
epinephrine (5μg/ml)
Type: General
anaesthesia
Dose:
thiopentone
Post op: 4-6 ml of
0.5% bupivacaine with
epinephrine ever 4
hours for 16 hours
Post-op:
Parenteral
analgesics on
demand
Timing: Prolonged
Intervention: Mean into post-op period for
pain relief
age: 66.5±5.5 yrs
M/F:7/8
Additional nonControl: Mean age: comparative
prophylaxis:
65.4±6.3 M/F:8/7
Physiotherapy
program with early
ambulation
Length of
follow up
Scanning
was
performed
14 days
before
surgery and
14 days
postoperati
vely
Outcome
measures
DVT Confirmed
by: Bilateral
venography on
th
14 post-op day
Int: 5/15
Control: 11/15
p value: 0.0281
Proximal DVT
Confirmed by:
Int: 3/15
Control: 11/15
p value: <0.05
PE
Confirmed
by: all patients
had V/Q scan on
th
14 post-op day
Int: 2/15
Control: 7/15
p value: Not
significant
Timing:
Intraoperatively.
Additional noncomparative
prophylaxis:
Physiotherapy
program with early
ambulation
Only 3 PEs (all in
control group) were
symptomatic
Bleeding related
complications
Intraoperative
blood loss: (no
measurement
criteria)
Post-operative
blood loss: (no
measurement
criteria)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
454 of 648
Effect size
Intraoperative
blood loss:
Int: 1100±316 ml
Control:
1757±426ml
p
value: <0.001
(Significant)
Postoperative
blood loss:
Int: 1200±350 ml
Control: 1800±400
ml
p value:
<0.001 (Significant)
Comments
Not reported: PTS,
QoL, survival, LoS,
funding
DRAFT FOR CONSULTATION
Regional vs general anaesthesia
Bibliographic
reference
Nielsen et al,
386
1990
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Nos
randomise
d:
Total: 36
Intervention
: n = 18
Control: n =
18
Type of surgery:
primary or revision
knee arthroscopy
Duration of
surgery:
Intervention: median
80 (55-100) min
Control: min
7 patients
withdrawn
–5
epidural, 2
general
Intervention:
Median age: 70
(range 46-87) yrs
M/F:5/13
Control: Median
age: 65 (range3885) M/F:6/12
Pre-existing risk
factors: Cardiac
disease, varicose
veins. Higher BMI in
control group
Intervention
Comparison
Type: lumbar epidural
anaesthesia Dose:
2% mepivacain
Type: general
anaesthesia
Dose:
Additional noncomparative
prophylaxis: Thighlength stocking on
contralateral leg pre-op
until full ambulation.
Calf-length stocking on
operated leg
immediately post-op
until ambulation. Quad
excercises on 1st postop day, active knee
mobilisation with full
weight bearing from
nd
2 day.
Additional noncomparative
prophylaxis:
Thigh-length
stocking on
contralateral leg
pre-op until full
ambulation. Calflength stocking on
operated leg
immediately postop until
ambulation. Quad
st
excercises on 1
post-op day,
active knee
mobilisation with
full weight bearing
nd
from 2 day.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
455 of 648
Length of
follow up
Outcome
measures
Both
groups: 911 days
post-op
DVT Confirmed
by: bilateral
ascending
venography on 9th
11 day post-op
Int: 2/13
Control: 10/16
p value: <0.05
Proximal DVT
Confirmed by:
bilateral
ascending
venography on 9th
11 day post-op
Int: 1/13
Control: 3/16
p value: Not
reported
Bleeding related
complications
Suction drain
volume
Median suction
drain volume:
Int: 1060 (340-1940)
ml
Control: 990 (1953275)
p value: >0.4 Not
significant
Effect size
Comments
Not reported:
PTS, PE,QoL,
survival, LoS,
funding
DRAFT FOR CONSULTATION
Regional vs general anaesthesia
Bibliographic
reference
Poikolainen
and Hendolin
411
1983
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 38
Intervention
: n = 17
Control: n =
21
Patients
characteristics
Type of surgery:
Prostatectomy
Duration of
surgery:
Intervention: 71±3
min Control: 74±3
min
Intervention
Type: lumbar epidural
anaesthesia Dose:
Butanilicaine 2%
Comparison
Type: General
anaesthesia
Dose:
Thiopentone
Additional noncomparative
prophylaxis:
Not reported
Intervention: All
male
Mean age: NR. No
differences between
groups for age
Control: All male
Mean age: NR. No
differences between
groups for age
Pre-existing risk
factors: NR. No
differences between
groups
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
456 of 648
Length of
follow up
NR
Outcome
measures
DVT Confirmed
by: 125I FUT test
(timing NR).
Positive result
confirmed by
venography
Effect size
Int: 2/17
Control: 11/21
p value: <0.02
(Significant)
Comments
Comments: Study
measured changes
in flow velocity in
femoral vein.
Induction of
epidural
anaesthesia led to
significant increase
in velocity of blood
flow in femoral vein
(p<0.001), whereas
flow velocity fell
significantly with
general
anaesthesia.
DRAFT FOR CONSULTATION
Evidence Table 61: Regional + general vs general anaesthesia
Bibliographic
reference
Dauphin et al
121
1997
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Total: 37
Patients
characteristics
Type of surgery:
Total hip
Intervention arthroplasty
: n = 20
Duration of
Control: n = surgery:
Intervention
17
2.28±0.27 hr.
(40
randomised Control: 2.5±5.3
– 3 dropIntervention: Mean
outs)
age: 70.9±6.7 yrs
M/F:7/13
Intervention
Comparison
Type: General
anaesthesia plus
lumbar epidural
anaesthesia Dose:
General: Thiopental
sodium. Specific drug
and dose chosen by
anaesthesiologist
Epidural: 10 ml 0.5%
bupivacaine
Type: General
anaesthesia
Dose: Thiopental
sodium. Specific
drug and dose
chosen by
anaesthesiologist
Timing: For the
operative period
Additional noncomparative
prophylaxis:
Coumadin daily
st
from 1 post-op
day until
discharge.
Control: Mean age: Additional non66.2±14.3 M/F:7/10 comparative
prophylaxis:
Coumadin daily from
1st post-op day until
discharge.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Timing: For the
operative period
Length of
follow up
125
Daily I
scan for 3
days,
impedence
plethysmog
raphy on
days 5,7
and 9 and
venography
on the
planned
day of
discharge
Outcome
measures
Comments
DVT Confirmed
125
by: I FUT test
daily for 3 days
post-op.
Venography on
day of discharge
Int: 4/20
Control: 4/17
p value: 0.79
Comments:
Possible error in
standard deviation
of surgery duration
in control group
(5.3hrs!). Paper
reports no
significant
difference between
the two groups in
operation length.
Bleeding related
complications
Intraoperative
blood loss:
sponge weights
and suction bottle
contents
Intraoperative
blood loss:
Int: 663.8±299.0
Control:
1259.2±366.0
p value: <0.001
Not reported:
Proximal DVT, PE,
PTS, QoL, LoS,
survival
Post-operative
blood loss:
measured from
wound drainage
(using the Dalvol
Reliavac 400
system)
457 of 648
Effect size
Post-operative
blood loss:
Int: 444.0±300.8
Control:
600.8±390.8
p
value: 0.18
Total blood loss:
Int: 1107.8±378.6
Control:
1860.0±616.6
p value: <0.001
DRAFT FOR CONSULTATION
Evidence Table 62: Foot elevation
Bibliographic
reference
Study
Type
RCT
Rosengarten
and Laird
1971(ROSEN
GARTEN1971
A}
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 25
Intervention
:n=
Control: n =
Type of surgery:
Elective surgery
(operations on leg
below groin
excluded)
(&
Duration of surgery)
Intervention
Comparison
Nil prophylaxis
Type: Leg elevation
Dose: Both legs
elevated at 15 degrees
Timing: From
premedication
(including during
Intervention: Mean surgery) until 1 week
post-op. Ambulation
age: 58.6±11.1 yrs
allowed but patients
M/F:6/6
discouraged from
Control: Mean age: sitting.
58.0±12.4 yrs
Additional nonM/F:6/7
comparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Length of
follow up
NR
Outcome
measures
Effect size
DVT Confirmed
125
by: Bilateral I
FUT daily (for 3
weeks?)
Int: 4/12
Control: 4/12
p value: 0.9
3/8 DVTs were
symptomatic
Proximal DVT
Confirmed by:
Int: 1/12
Control: 1/12
p value: N/A
Comments
Comments: Mean
duration of
increased activity in
legs denoting
presence of
thrombosis was
5.0±2.5 days in
intervention and
10.8±4.1 in the
control group
Not reported: PE,
PTS, QoL, LoS,
survival, bleeding
458 of 648
DRAFT FOR CONSULTATION
Evidence Table 63: Hydration
Bibliographic
reference
Janvin 1980
257
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Total: 60
Type of surgery:
Routine abdominal
Interventio surgery (any patient
requiring blood
n: 30
transfusions
Control: 30 perioperatively was
withdrawn from the
Dropouts: trial).
3
Intervention: Mean
age: 57±10 yrs
M/F:15/15
Control: Mean age:
58.0±12 yrs M/F:
12/18.;
Intervention
Type: Intravenous
Hartmann’s solution/
Dextose-saline
Dose and timing: 1
litre of per hour of
operation. 2-3 litres of
dextrose saline 24hs
for 2 days.
Additional noncomparative
prophylaxis:
Not reported
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comparison
Type: No IV fluids
during or
postoperatively.
Water by mouth.
Dose: “Small,
increasing
amounts of water
were taken by
mouth from the
first day onwards”.
Timing:
Not reported
Additional noncomparative
prophylaxis:
Not reported
459 of 648
Length of
follow up
7 days
Outcome
measures
Effect size
DVT measured by Int: 9/30
Cont: 2/30
FUT. Bilateral
p value: <0.03
daily then
alternate days.
Comments
Comments:
Three dropouts, but
analysis by
denominators of 30,
i.e. presumably
analysed by
intention to treat.
Also measured risk
factors (varicose
veins, smoker, etc),
impendance
clotting time and
packed cell volume.
Not reported: PE,
PTS, QoL, LoS,
survival, bleeding,
proximal DVT.
DRAFT FOR CONSULTATION
Evidence Table 64: Vena caval filters vs no filters
Bibliographic
reference
Decousus et
128
al 1998
Long term
follow up at 8
years
published by
The PREPIC
Study Group
498
(see next
entry)
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Intervention
Comparison
Type: Permanent vena No filter
Caval filter 4 types:
Vena Tech LGM,
Additional nontitanium Greenfield,
Cardial and Bird's nest comparative
prophylaxis: All
patients received
Control: n = Intervention: Mean Timing: Inserted
OAC from 4th day
through femoral or
age: 73±11 yrs
200
and for at least 3
jugular vein
M/F:92/108
months. Patients
immediately after
randomised to
Control: Mean age: randomisation
receive either
72±11.5 M/F:98/102
UFH or LMWH for
Additional non8-12 days
comparative
Pre-existing risk
prophylaxis: All
factors: History of
patients received OAC
VTE, Chronic
from 4th day and for at
cardiac or
least 3 months.
respiratory
Patients randomised to
insufficiency,
receive either UFH or
Surgery in past 60
LMWH for 8-12 days
days, cancer,
symptomatic initial
PE
Total: 400
Hospitalised
patients: with
proximal DVT
Intervention considered to be at
high risk for PE
: n = 200
Length of
follow up
Both
groups:
visits at 4
months and
1 year.
Telephone
follow up at
2 yrs
Outcome
measures
Symptomatic &
asymptomatic
PE
on 8-12th
day
460 of 648
Int: 2/200
Control: 9/200
p value: 0.05
Symptomatic PE Int: 6/200
Control: 12/200
at 2 yrs
Confirmed by: V/Q p value: 0.16
scan
Additional
Fatal PE Based
follow-up at
on clinical
8 years
diagnosis
Int: 1/200
Control: 5/200
p value: 0.14
Recurrent DVT at Int: 37/200
Control: 21/200
2 years: Clinical
p value: 0.03
suspicion
investigated with
venography
Major bleeding at Int: 9/200
12 days: *
Control: 6/200
p value: 0.17
Major bleeding at Int: 17/200
2 years: *
Control: 22/200
p value: 0.40
All cause
mortality: At 12
days
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Effect size
Int: 5/200
Cont: 5/200
P value 1.00
Comments
Comments: 2x2
factorial design.
Patients also
randomised to
receive either UFH
or LMWH.
Denominators used
for analysis of
primary outcomes
unclear.
Thrombosis at filter
site was found in 16
patients.
At 2 years there
were no significant
differences
between groups in
all principal endpoints symptomatic PE,
recurrent DVT,
major bleeding,
death.
* Major bleeding
described as Overt
haemorrhage that
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Evidenc
e level
No. of
patients
Patients
characteristics
Intervention
Comparison
Length of
follow up
Outcome
measures
All cause
mortality: At 2
years
Effect size
Int: 43/200
Cont: 40/200
P value 0.71
Comments
was fatal or
required transfusion
of at least 2 units of
red cells, surgical
intervention, or
cessation of
treatment
Not reported: QoL,
PTS, funding
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
461 of 648
DRAFT FOR CONSULTATION
Vena caval filters vs no filters
Bibliographic
reference
The PREPIC
Study
498
Group
This study is
the long term
follow up at 8
years of the
RCT
published by
Decousus et
128
al, 1998
Study
Type
RCT
Evidenc
e level
1+
No. of
patients
Patients
characteristics
Intervention
Comparison
Type: Permanent vena No filter
Caval filter 4 types:
Vena Tech LGM,
Additional nontitanium Greenfield,
Cardial and Bird's nest comparative
prophylaxis: All
patients received
Control: n = Intervention: Mean Timing: Inserted
OAC from 4th day
through femoral or
age: 73±11 yrs
200
and for at least 3
jugular vein
M/F:92/108
months. Patients
immediately after
randomised to
Control: Mean age: randomisation
receive either
72±11.5 M/F:98/102
UFH or LMWH for
Additional non8-12 days
comparative
Pre-existing risk
prophylaxis: All
factors: History of
patients received OAC
VTE, Chronic
from 4th day and for at
cardiac or
least 3 months.
respiratory
Patients randomised to
insufficiency,
receive either UFH or
Surgery in past 60
LMWH for 8-12 days
days, cancer,
symptomatic initial
PE
Total: 400
Hospitalised
patients: with
proximal DVT
Intervention considered to be at
high risk for PE
: n = 200
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
462 of 648
Length of
follow up
8 years
Outcome
measures
Effect size
Symptomatic PE Int: 9/200
Control: 24/200
at 8 yrs
Confirmed by: V/Q p value: 0.009
scan
Fatal PE at 8 yrs
Based on clinical
diagnosis
Int: 2/200
Control: 5/200
p value: 0.27
Int: 57/200
Symptomatic
venous thrombo- Control: 41/200
p value: 0.74
embolism at 8
yrs
Post-thrombotic
syndrome at 8
years:
Int: 109/200
Control: 107/200
p value: 0.84
Major bleeding at Int: 26/200
8 years: *
Control: 31/200
p value: 0.48
Mortality at 8
years
Int: 26/200
Cont: 31/200
P value 0.62
Comments
* Major bleeding
described as Overt
haemorrhage that
was fatal or
required transfusion
of at least 2 units of
red cells, surgical
intervention, or
cessation of
treatment
Not reported: QoL,
funding
DRAFT FOR CONSULTATION
Evidence Table 65: Economic evidence tables
Bibliographic
reference
Study Type
Abdool-Carrim
3
et al, 1997
Economic
analysis:
Costeffectiveness
analysis
South Africa
Study
design:
Decision
analysis
based on
literature
review and
postal survey
of 12
surgeons
Patients
characteristic
s
Type of
surgery:
Elective hip
replacement
(Duration of
surgery=NR)
Mean age: NR
M/F:NR
Pre-existing
risk-factors:
NR
Interventions
Outcome measures
Effect size
Comments
1: Venogram surveilance
Details: NR Timing: Day 7
DVT
1: 50% 2: 26% 3: 21% 4: 29% 5: 24%
6: 35% 7: 50%
2: LMWH Dose: 40mg/day
Timing: 10 days
Bleeding related
complications Serious
haemorrhage
Death
1: 0% 2: 2% 3: 2% 4: 4% 5: 4% 6:
0.7% 7: 0%
Funding: Rhone-Poulenc
Rorer - J Henderson, L
Moekoena
3: LMWH+GECS Dose:
40mg/day / above-knee
Timing: 10 days
4: LDUH Dose: 5000U 3x
daily Timing: 10 days
5: LDUH+GECS Dose:
5000U 3x daily / above-knee
Timing: 10 days
Time
horizon: NR:
<12 months
6: Aspirin+GECS Dose:
300mg/day / above-knee
Timing: 10 days
Discount
rates:
NA
7: NIL
Additional non-comparative
prophylaxis:
NR
Mean cost (S.A. Rand;
prophylaxis, DVT
treatment/diagnosis, PE
treatment/diagnosis,
bleed treatment)
Cost-effectiveness:
1: 0.7% 2: 1.1% 3: 0.9% 4: 1.2% 5:
1.0% 6: 1.5% 7: 2.1%
1: 3017 2: 1223 3: 1311 4: 1264 5:
1351 6: 777 7: 875
Lives saved
2, 4, 5 and 7 are dominated
3 vs 6: R89,000 per life saved
1 vs 3: R1,706,000 per life saved
DVTs averted
1, 2, 4, 5 and 7 are dominated
3 vs 6: R3814 per DVT averted
Sensitivity analysis:
(selective one-way
analysis)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
463 of 648
LMWH (and Warfarin) become more
cost-effective when one focuses on
proximal DVTs
Outcomes not included:
PTS, HRQL, LE
Other comments: Since
this is a model, p-values, etc
are NA
DRAFT FOR CONSULTATION
Bibliographic
reference
Alho et al,
12
1984
Norway
Study Type
Economic
analysis:
Cost
consequence
s
Study
design:
Cohort
Time
horizon:
90 days
Discount
rates:
NA
Patients
characteristics
Type of
surgery:
Hip fracture
Mean age: NR
M/F:NR
Pre-existing
risk-factors:
Age>40
Interventions
1: Heparin Dose:
5000 U s.c. Timing:
14 days or longer, until
independent mobility
2: Aspirin Dose:
500mg twice daily
Timing: 14 days or
longer, until
independent mobility
Outcome measures
Effect size
Comments
DVT Confirmed by:
phlebography
1: 4.2% 2. 3.0% 3. 2.5%
Funding: NR
PE
Confirmed by: chest x-ray
followed by ventilation/perfusion
scanning in negative and
equivocal cases
1: 2.1% 2. 0.5% 3. 0.5%
Outcomes not included:
FPE, PTS, Bleeding,
HRQL, Survival, LE
Mean cost (1981 Norwegian
Crowns (NOK), Direct medical
costs of prophylaxis and
diagnosis/treatment of VTEs)
1: 968 2. 345 3. 457
3: Warfarin Dose:
Cost-effectiveness:
5000 U s.c. Timing:
14 days or longer, until
independent mobility
Cost per PE
1 and 3 were dominated by 2
Cost per DVT
1 was excluded due to dominance
3 vs 2: 22,400 NOK per extra DVT averted
Additional noncomparative
prophylaxis:
NR
Not conducted
Sensitivity analysis:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
464 of 648
DRAFT FOR CONSULTATION
Bibliographi
c reference
Study Type
Anderson et
16
al, 1993
Economic
analysis:
Cost & Cost
Effectiveness
Analysis
Canada
Patients
characteristic
s
Type of
surgery:
Total Hip
Arthroplasty
Interventions
Outcome measures
Effect size
Comments
Int: LMWH Enoxaparin
Dose: 30mg twice daily
subcutaneous
Timing: 14 days
DVT Confirmed by: NR
Reported as a) Distal and b)
Proximal
a)
Int: 5.4%
Control: 12.6%
p value: (sig: OR=0.40, 95%CI=[0.280.59])
Study design:
Meta analysis
of RCTs
Intervention:
Low Molecular
Weight
Heparins
Control: Standard
Heparin Dose: 7500U
twice daily subcutaneous
Timing: 14 days
b)
Int:11.0%
Control:9.2%
p value: (Not sig, OR=1.22,
95%CI=[0.86-1.74])
Funding: Canadian
Heart and Stroke
Foundation, Medical
Research Council of
Canada, University of
Ottawa
Time horizon:
Short term
evaluation
N: NR
Mean age: NR
M/F:NR
Additional noncomparative
prophylaxis:
Total DVT
OR=0.70, 95%CI=[0.53-0.92]
OR=0.22, 95%CI=[0.05-0.88].
Discount
rates:
Costs=Not
Applicable
Effects=Not
Applicable
Control:
Standard
Heparin
N: NR
Mean age: NR
M/F:NR
PE
Confirmed by: NR
LMWH significantly reduces chances of PE
(few cases though)
Bleeding related
complications (Meta
analysis of 6 studies, reported
as a) Major bleeding and b)
Minor bleeding)
Pre-existing
risk-factors:
a)
Int: 1.8%
Control: 2.9%
p value: (Not sig: OR=0.64,
95%CI=[0.34-1.23])
b)
Int:6.8%
Control:7.3%
p value: (Not sig, OR=0.92,
95%CI=[0.61-1.33])
Survival (pooled number of
deaths)
Mean cost (Costs in 1992
US$. Costs included are:
Prophylaxis, Management of
DVT, Management of
Bleeding)
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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Total Bleeding
OR=0.82, 95%CI=[0.58-1.15]
Int: 0.13% (1/735)
Control: 0.43%
(3/685)
p value: NR
Int: $340.206
Control: $388.149
p value: NR
Outcomes not included:
HRQL, Post-thrombotic
leg, LOS, LE
DRAFT FOR CONSULTATION
Cost-effectiveness: (Cost per
DVT averted)
LMWH dominates SH in the base case,
when the Price ratio is estimated to be 2.6
Sensitivity analysis:
ICER is $1020 when the Price Ratio is 5
and $5082 when the Price Ratio is 10.
Break Even Point is Price Ratio=3.7
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
466 of 648
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Annemans et al, Economic
20
analysis:
2004
Cost
consequen
Belgium
ces
analysis
Study
design:
Decision
analysis
(based on
established
489
model
Time
horizon:
5 years
(also one
year and
90 days –
not
reported
here)
Discount
rates:
NR
Patients
characteristics
Type of surgery:
A. Total hip
replacement
B. Total knee
replacement
C. Hip fracture
Mean age: NR
M/F:NR
Interventions
Int: Fondaparinux
Dose: NR
Timing: Postop for 7
days
Control: Enoxaparin
Dose: NR
Timing: Postop for 7
days
Pre-existing risk- Additional noncomparative
factors:
prophylaxis:
NR
NR
Outcome measures
Effect size
DVT Confirmed by: NR
A. Int: 1.8% Control: 2.7%
B. Int: 1.5% Control: 2.7%
C. Int: 3.2% Control: 4.5%
Confirmed by: NR
A. Int: 0.6% Control: 1.1%
B. Int: 0.7% Control: 1.2%
C. Int: 1.0% Control: 1.8%
PE
Fatal PE
Confirmed by: NR
A. Int: 0.1% Control: 0.2%
B. Int: 0.1% Control: 0.2%
C. Int: 0.7% Control: 1.3%
VTE recurrence Confirmed by:
NR
A. Int: 0.2% Control: 0.3%
B. Int: 0.2% Control: 0.4%
C. Int: 0.2% Control: 0.4%
Post thrombotic leg
A. Int: 3.0% Control: 3.6%
B. Int: 3.0% Control: 4.8%
C. Int: 3.1% Control: 4.1%
Bleeding related complications
Major bleed
A. Int: 2.9% Control: 2.7%
B. Int: 2.9% Control: 2.7%
C. Int: 2.9% Control: 2.8%
Cost (Euro; Direct medical costs
for prophylaxis, treatment of PE,
DVT, recurrence, PTS, Major
bleeding, false positives)
A. Int: €324 Control: €330
B. Int: €321 Control: €363
C. Int: €372 Control: €413
Cost-effectiveness:
Fondaparinux was cost saving and reduced
the number of VTEs for all three patient
groups
Sensitivity analysis:
In the long term (5 years), fondaparinux was
cost saving for all scenarios. At 90 days
fondaparinux was adding to cost.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
467 of 648
Comments
Funding: NR
Outcomes not included:
HRQL, LE
Other comments: Since
this is a model, p-values,
etc are NA
DRAFT FOR CONSULTATION
Bibliographic
reference
Bhatia 1998
Canada
58
Study
Type
Economic
analysis:
Cost
analysis
Patients
Patient group:
Patients who had
a vena cava filter
Intervention:
N:15
Study
Mean age: 63
design:
Retrospecti M/F:9/6
ve, before
and after
Control:
N:15
Time
Mean age: 55
horizon:
M/F:8/7
NA
Discount
rates: NA
Interventions
Outcome measures
Effect size
Int: Radiologic
percutaneous
placement of vena
tech LGM filter
PE
Int: 0
Mean Cost (Canadian $, year not
specified, product and
administration costs)
Int:$1580 (£1193) Control: $2282 (£1723)
Control: Surgical
cutdown of 24 Fr
Greenfield filter
Converted to £ using PPPs
NR
Sensitivity analysis:
Additional noncomparative
prophylaxis: NR
Funding: NR
Outcomes not included:
DVT FPE, PTS, Bleeding,
HRQL, Survival, LOS, LE,
Other limitations:
(1) Small patient numbers
(2) Bias associated with
before and after studies
Other comments:
Most of the difference in
cost was due to the cost of
supplies and the cost of the
product itself.
Pre-existing riskfactors: NR
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Control: 0
Comments
468 of 648
DRAFT FOR CONSULTATION
Bibliographi
c reference
Study Type
Patients
characteristic
s
Interventions
Outcome measures
Effect size
Comments
Bergqvist
and
Matzsch,
55
1993
Economic
analysis: Cost
Effectiveness
Analysis
Type of
surgery:
General
surgery or Hip
Arthroplasty
Int: LMWH
Dose: NR
Timing: 7 days (General
Surgery), 10 days (Hip
Arthroplasty)
DVT Confirmed by: NR
General Surgery
Int: 1.0%
Control1: 3.3%
Control2: 11.0%
Funding: NR
Intervention:
Low Molecular
Weight
Heparins
N: 1000
Mean age: NR
M/F:NR
Control1: UFH
Dose: NR
Timing: 7 days (General
Surgery), 10 days (Hip
Arthroplasty)
Sweden
Study design:
Pull of data
from several
studies (Not
proper
Metaanalysis)
Time horizon:
Short term
Discount
rates:
Costs=Not
Applicable
Effects=Not
Applicable
Control1:
Unfractionated
Heparins
Control2: No
prophylaxis,
but treatment
of VTE
Pre-existing
risk-factors:
Fatal PE
Confirmed by:
Control2: No prophylaxis
Dose: Not Applicable
Timing:
Additional noncomparative
prophylaxis:
Mean cost (Costs are in 1992
Swedish Crowns, SEK. Costs
included are: Prophylaxis,
Thromboembolitic
complications, Hemorrhagic
complications)
Outcomes not included:
PVT, PE, HRQL, Postthrombotic leg, Bleeding,
Survival, LOS, LE
Orthopaedic Surgery
Int: 2.3%
Control1: 6.9%
Control2: 23%
General Surgery
Int: 0.05%
Control1: 0.3%
Control2: 0.8%
Orthopaedic Surgery
Int: 0.1%
Control1: 0.3%
Control2: 2.4%
General Surgery
Int: SEK414
Control1: SEK866
Control2:
SEK2475
Cost-effectiveness: (Cost per
DVT averted)
Orthopaedic Surgery
Int: SEK902
Control1: SEK1727
Control2:
SEK5161
Prophylaxis proves to be cost effective, and
LMWH are better than UFH
Sensitivity analysis:
Poor, deterministic, to confirm the results
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
469 of 648
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Economic
Bergqvist and
52
analysis:
Jonsson, 1999
Costeffectivene
Sweden
ss
Study
design:
Decision
analysis
based on a
49
RCT
Time
horizon:
Lifetime
Discount
rates:
NR
Patients
Interventions
Type of surgery:
Total hip
replacement
Int: Continuous
prophylaxis with
enoxaparin Dose:
40mg/daily Timing:
Study start after an
average of 9 days on
enoxaparin. Study end
19 to 23 days after
discharge
DVT
(Venographic)
Int: 16% Control: 33%
Symptomatic DVT
Int: 2% Control: 5%
PE (non-fatal)
Int: 0% Control: 2%
Fatal PE
Int: 0% Control: 0%
Bleeding related complications
No increased incidence in bleeding reported
in trial
Control: Placebo
Timing: Average of 9
days on enoxaparin,
then placebo until 19
to 23 days after
discharge.
Length of Hospital Stay (days)
for patients treated for DVT or
PE
Int (n=10): 7.8 Control (n=35): 7.49
Mean Cost (SEK, year not
specified, cost of enoxaparin,
administration and treatment of
DVT only)
Cost of initial enoxaparin:
Int: 324 Control: 324
Cost of extended enoxaparin
Int: 585 Control: 0
Cost of hospitalisation:
Int: 2439 Control: 6447
Cost of administration of enoxaparin
(assuming 0% patients can administer
injection at home)
Int: 6510 Control: 0
Cost-effectiveness:
Life year gained calculated under
the following assumptions:
1. 0.003 life-years gained per
patient (assumptions related to
association between PE and
survival)
2. 0.006 life-years gained per
patient
Assuming 75% of patients can self-inject:
Cost per DVT and clinical DVT avoided dominated
All Patients:
N:262
Mean age: 68.5
M/F:43%/57%
Intervention:
N:131
Mean age: NR
M/F:NR
Drop-outs:NR
Control:
N:131
Mean age:NR
M/F:NR
Drop-outs:NR
Additional noncomparative
prophylaxis: All
patients received
Pre-existing risk- prophylaxis with
enoxaparin for an
factors: NR
average of 9 days.
Outcome measures
Effect size
1. 235,000 SEK per life year gained
(£16,204)
2. 120,000 SEK per life year gained (£8,274)
Converted to £ using PPPs
Sensitivity analysis:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Assuming 0% of patient can self-inject:
16,850 SEK per DVT avoided
57,771 SEK per clinical DVT avoided
(no additional analyses were done for life
year gained)
470 of 648
Comments
Funding: Swedish
Medical Research Council
and Rhone-Poulenc Rorer.
Outcomes not included:
PVT, PTS, Bleeding,
HRQL, Survival, LOS.
Other limitations
1. Limited to cost data on
drug, administration and
treatment of DVTs.
2. Data obtained from a
clinical trial therefore
compliance is high and
phlebography is not used in
normal clinical practice to
measure outcome.
3. Cost-effectiveness
estimates highly sensitive
to assumptions made about
no. patients that can selfinject
Other comments:
Since this is a model, pvalues, etc are NA.
DRAFT FOR CONSULTATION
Bibliographic
reference
Bischof et al,
60
2006
Country:
Switzerland
Study
Type
Patients
Interventions
Economic
analysis:
CEA, cost
per life year
gained
Type of surgery:
hip fracture
patients,
(HFS)
Int: Fondaparinux
Dose:
Timing:1
week (duration) (time
started) (time finished)
Study
design:
decision
analysis
Effect size
Incremental Cost-Effectiveness
ratio, 30 days, base case
HFS: CHF 2801 per life year gained
THR: 20,294 per LYG
Sensitivity analysis,
Fondaparinux costs, 30 days
(range: CHF 13-20)
HFS: CHF 1586-3885 per LYG
THR: CHF13964-25938 per LYG
Hip replacement
patients (THR)
Sensitivity analysis, cost DVT
after discharge, 30 days,
(range: CHF 1950-9750)
HFS: CHF 2362-3191 per LYG
Interventions:
Fondaparinux
extended(1
month) versus
Fondaparinux (1
week) THR
Sensitivity analysis, cost of PE
after discharge, 30 days, (
range: CHF 9018 -15372)
HFS: CHF 9018-15372 per LYG
THR: CHF 18974-21291 per LYG
N: 1000
Time
Mean age: 65
horizon:
M/F:NS
30 days
and 5 years
Discount
rates:
Costs=4%
Effects
=4%
Outcome measures
Int: Fondaparinux
Dose:
Timing: 1
month
Additional noncomparative
prophylaxis:
Interventions:
Fondaparinux
extended(1
month) versus
Fondaparinux (1
week) (HFS)
N: 1000
Mean age: 76
M/F:NS
Pre-existing riskfactors:
NR
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
471 of 648
Comments
Funding:
Sanofi-Synthelabo SA
Outcomes not included:
DVT PE, FPE, PTS,
Bleeding, HRQL, Survival,
LOS, LE,
THR: CHF 16555-23618 per LYG
Other comments:
The study report only
incremental results, and not
mean results.. The study
presents also many others
univariate sensitivity
analyses, varying the value
ofunit cost of a particular
condition, however those
reported are the ones that
make the results more
sensitive.
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Bjorvatn and
Kristiansen,
62
2004
Type of surgery:
A. Total hip
replacement
Mean age: 71.6
M/F:28%/72%
B. Total knee
replacement
Mean age: 69.7
Study
M/F:30%/70%
design:
C. Hip fracture
Decision
Mean age: 78.8
analysis
M/F:29%/71%
(based on
established Pre-existing risk489
factors:
model
NR
Time
horizon:
90 days
(also 5
years but
details
were not
reported in
the paper)
Norway
Economic
analysis:
Cost
consequen
ces
analysis
Patients
characteristics
Interventions
Outcome measures
Effect size
Comments
Int: Fondaparinux
Dose: 2.5mg daily
Timing: Postop for 7
days
DVT Confirmed by: NR
A. Int: 1.8% Control: 2.7%
B. Int: 1.5% Control: 2.7%
C. Int: 3.1% Control: 4.5%
Funding: NR
Control: Enoxaparin
Dose: 40mg daily
Timing: Preop for 7
days
Additional noncomparative
prophylaxis:
NR
PE
Confirmed by: NR
Fatal PE
Confirmed by: NR
A. Int: 0.6% Control: 1.1%
B. Int: 0.7% Control: 1.2%
C. Int: 1.0% Control: 1.8%
A. Int: 0.1% Control: 0.2%
B. Int: 0.2% Control: 0.4%
C. Int: 0.5% Control: 0.8%
A. Int: 2369 Control: 2209
Cost (Norwegion Kroner, Direct
B. Int: 2259 Control: 2107
medical costs for prophylaxis,
treatment of PE, DVT, recurrence, C. Int: 2840 Control: 2922
PTS, Major bleeding)
Cost-effectiveness:
A. Fondaparinux cost 200,000Kr per death
averted
B. Fondaparinux cost 89,400Kr per death
averted
C. Fondaparinux was both cost saving and
saved lives
Sensitivity analysis:
Fondaparinux appears to be cost-effective
under a number of different scenarios
Discount
rates:
Costs: 3%
Effects: NR
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
472 of 648
Outcomes not included:
HRQL, LE (the cost of
bleeding and PTS are
included in the model but
the number of such events
are not reported in the
paper)
Other comments: Since
this is a model, p-values,
etc are NA
DRAFT FOR CONSULTATION
Bibliographic reference
Borris et al, 1994
Denmark
69
Study Type
Patients
characteristics
Type of surgery:
Economic
Elective hip
analysis:
surgery
Cost
effectiveness
analysis
Mean age: NR
M/F:NR
Study
design:
MetaPre-existing riskanalysis
factors:
NR
Time
horizon:
NR
Discount
rates:
NR
Interventions
Outcome measures
Effect size
Comments
1: No prophylaxis
DVT (difference in
rates)
4 vs 1: -18.7%
4 vs 2: -15.4%
4 vs 3: -7.4%
Funding: NR
2: Dextran 70 (8
days)
PE (difference in rates)
4 vs 1: -0.5%
4 vs 2: +0.5%
4 vs 3: -1.3%
Bleeding related
complications Major
bleed (difference in
rates)
4 vs 1: +0.0%
4 vs 2: -0.7%
4 vs 3: -0.8%
3: UFH (8 days)
4. LMWH (8 days)
Additional noncomparative
prophylaxis:
NR
4 vs 1: DKK1160 (£105)
Incremental cost
savings (Danish Krona; 4 vs 2: DKK1682 (£153)
4 vs 3: DKK1272 (£115)
prophylaxis costs,
nursing time, treatment
costs for symptomatic
VTEs major bleeding and
transfusions)
Cost-effectiveness:
LMWH dominates no prophylaxis.
Otherwise cost-effectiveness is difficult
to determine since dextran is more
effective at reducing PEs
Sensitivity analysis:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
473 of 648
NR
Outcomes not included: FPE,
PTS, HRQL, Survival, LOS, LE
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Patients
characteristic
s
Interventions
Outcome measures
Botteman et al,
72
2002
Economic
analysis:
Cost
effectivene
ss analysis
Type of
surgery:
Total Hip
Replacement
Int: Enoxaparin Dose: 30mg
BID
Timing: 7 days
DVT Confirmed by: Ultrasound,
Venogram
USA
Study
design:
Decision
Analytic
Model
Time
horizon:
Short term
+ Long
term
evaluation
Discount
rates:
Costs=3%
Effects (all
studied)=3
%
Intervention:
Enoxaparin
N: NR
Mean age: 72
yrs
M/F:35/65
Control:
Warfarin
N: NR
Mean age: 72
yrs
M/F:35/65
Pre-existing
risk-factors:
Control: Warfarin Dose:
5mg QD
Timing: 7 days
Additional non-comparative
prophylaxis:
PE
Confirmed by: NR
Survival (Markov model)
Effect size
Comments
Funding: NR
Int: 136/1000
Control:
213/1000
p value: NR
Int: 2.5%
Control: 2.5%
p
value:
Int: 7/1000
Control: 11/1000
p value: NR
Mean cost (US$, year 2000. Costs
included: 7 days prophylaxis,
Diagnosis of DVT, Extended
Hospitalisation, Physician visits,
Heparin treatment, Angiography)
Fatal PE
Confirmed by: NR
a) Short term scenario (decision tree)
b) Long term scenario (markov model)
a) Int: $286.04
p value: NR
term scenario)
Quality-adjusted life-years (used the
Quality of Well Being Scale.
Measured in terms of QALYs)
a) Short term scenario (decision tree)
b) Long term scenario (markov model)
a) Int: 8.82
value: NR
b) Int: 7.43
value: NR
Cost-effectiveness: (Cost per DVT
avoided, Cost per Death averted,
Cost per QALY saved, Cost
Effectiveness Acceptability curve)
a) Short term scenario (decision tree)
b) Long term scenario (markov model)
Sensitivity analysis: Univariate
deterministic & Probabilistic
Sensitivity Analysis (via Monte Carlo
simulation)
a) Cost per DVT averted: $1728
Cost per Death averted: $34477
Cost per QALY saved: $3733
b) Net lifetime savings of $89 per
patient and 0.16 QALYs (i.e. ~2
quality adjusted life-months) saved
Compared with Warfarin, the use of
Enoxaparin leads to net increases in
QALY & reduction of costs, in the
long run
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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Control: $76.38
(values for Short
a) Int: 7/1000
Control: 11/1000
p value: NR
b) Int: NR
Control: NR
p
value: NR
Control: 8.78
p
Control: 7.27
p
DRAFT FOR CONSULTATION
Bibliographic
reference
Brasel et al,
74
1997
Study
Type
Patients
Economic
analysis:
CEA
Patient group:
High risk trauma
patients
Study
design:
Decision
analysis
Patients: Model
assumes all
patients are high
risk, age > 45
years, pelvic
fracture, lower
extremity fracture
or venous repair,
Injury severity
score ≥ 15, or
spinal cord injury,
LOS ≥ 3 days
US
Time
horizon:
30 days
Discount
rates: NR
Interventions
Outcome measures
1. Duplex ultrasound,
PE (Incidence of PE)
twice weekly screening Mean Cost (US $, year not
specified, product and
2. Inferior vena cava
administration costs)
filters, inserted in
operating room
Converted to £ using PPPs
3. Subcutaneous
unfractionated heparin
(5 days) and warfarin
sodium (6 months)
and/or sequential
compression devices
Effect size
1. 0.02 2. 0.01 3. 0.04
1. $971 (£606) 2. $2856 (£1782) 3. $45
(£28)
Comments
Funding: NR
Outcomes not included:
DVT FPE, PTS, Bleeding,
HRQL, Survival, LOS, LE.
Other limitations:
Short-term time horizon
Cost-effectiveness: (cost per PE
prevented)
1 vs. 3: $46,300 (£28,891)
2 vs. 3: $93,700 (£58,469)
Sensitivity analysis:
Location of placement of vena cava filters
Other comments:
was identified as a sensitive variable. When
Since this is a model, pvena cava filters are placed in the operating
values, etc are NA
room then (1) is always more cost-effective.
When they are placed in radiology then (1)
and (2) have equivalent cost-effectiveness
until LOS > 2 weeks, when radiology
placement of (2) becomes more cost-effective
than (1).
Additional noncomparative
prophylaxis: All
patients were receiving
Pre-existing risk- subcutaneous
factors: High risk unfractionated heparin
and/or sequential
compression devices
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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DRAFT FOR CONSULTATION
Bibliographic
reference
Caprini et al
88
2002a
Study
Type
Patients
characteristics
Economic
analysis:
CEA
Type of surgery:
Elective total hip
replacement
Study
design:
Model
Mean age: NR
M/F: NR
Interventions
Intervention: LMWH
(Enoxaparin)
Control1: Warfarin
USA
Time
horizon:
NR
Discount
rates:
NR
Control2:
Combination of
Warfarin,
Unfractionated
Pre-existing risk- Heparin, Stockings &
Compression devices
factors: NR
Timing:
Mean duration of
prophylaxis:
LMWH: 7 days
Warfarin: 10-14 days
Combo: 10-14 days
Outcome measures
Effect size
Comments
Symptomatic VTE ,
Int: 4.9%
Control1: 2.5%
Control2: 3.08
p value: Not reported
Funding: Aventis and
Tyco
Bleeding related complications
(major bleeding)
Int: 1.2 %
Control1: 0.5%
Control2: 1%
p value: Not reported
Cost (US$, health care costs of
prophylaxius and treatment of
VTEs and major bleeding)
Int: vs control2: -$56
Outcomes not reported:
PVT, FPE, PTS, Bleeding,
HRQL, Survival, LOS, LE,
QALE
Cost-effectiveness: (cost per
VTE averted)
LMWH dominates
Sensitivity analysis: (one-way
sensitivity analyses on the cost of
prophylaxis and the cost of
treating bleeding)
The results were robust to the specific
sensitivity analyses conducted
Additional noncomparative
prophylaxis: NR
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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Other comments:
assumed clinical
outcomes.for the
combination. No measures
of uncertainty & limited
sensitivity analysis.
Results were also
presented in the context of
routine surveilance
DRAFT FOR CONSULTATION
Bibliographic
reference
Chau et al,
94
2003
Study
Type
Patients
Economic
analysis:
CUA
Patient group:
Patients with
malignant brain
tumours and DVT
of the lower
extremities
USA
Study
design:
Markov
model,
probabilitie
s obtained
from 24
patients in
s cancer
center.
Time
horizon:
Lifetime
Discount
rates:
Costs=3%
All patients:
N: 24
Mean age: 50
M/F:NR
Pre-existing riskfactors: DVT
Interventions
Int: Bird’s nest filter
and anticoagulation
(heparin).
Control:
Anticoagulation only
(heparin)
Additional noncomparative
prophylaxis: NR
Outcome measures
Effect size
Comments
PE (PE free months)
Int: 11.6 months Control: 9.4 months
(p=0.24)
Funding: NR
PE (rate of PE – per 100 personmonths at risk)
Int: 0.57 Control: 1.05 (no p value)
Survival (mean)
Int: 12.1 months Control: 9.5 months
(p=0.13)
Outcomes not included:
DVT PTS, Bleeding, HRQL,
LOS, LE.
Mean Cost (US $, 1999, costs
included all hospital costs
associated with a PE)
Int: $7,502 (£4,821) Control: $4,730
(£3,046)
Converted to £ using PPPs
Other limitations:
1. Probability data based
on a small sample size of
nonrandomised, noncontrolled patients, in which
there was a survival
difference between the two
groups.
2. Survival time was short –
filters may be more costeffective for groups of
patients with longer survival
times.
Quality-adjusted life-years
(utility value of 0.7 was assigned
to a PE from Tengs et.al. 2000)
Int: 2.34 Control: 2.33
Cost-effectiveness: (cost per
QALY)
ICER = $198,852 (£128,061)
Sensitivity analysis: Rate of PE,
cost of PE and 5-yr mortality rate
were all varied.
Rate of PE of control would have to exceed
1.51 for ICER < $50,000
Cost of PE would have to exceed $35,000 for Since this is a model, pvalues for costs, etc are NA
the filter to be a cost-effective strategy.
The 5-yr mortality rate was varied using
survival data from patients with lung cancer
and breast cancer. In patients with a longer
LE filters could be cost-effective.
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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DRAFT FOR CONSULTATION
Bibliographic
reference
Study Type
Patients
characteristics
Interventions
Outcome measures
Effect size
Comments
Dahl and Pleil,
119
2003
Economic
analysis: Cost
analysis
Type of surgery:
Total Hip
Replacement
Int: Dalteparin Dose:
5000IU subcutaneous
Timing: daily 7-15 days
post op, with no outpatient continuation
DVT Confirmed by:
Venography
Funding:
Pharmacia
Corp and
Pharmacia UK
Ltd
Study design:
Data selected
from Literature
Review
Intervention:
Dalteparin 7-15 days
post op
N: NR
Mean age: NR
M/F:NR
Int: 8.5% (25%-75% percentiles: 1.3%30.0%)
Control1: 5.5% (25%-75%
percentiles: 0.9%-19.4%)
Control2: 8.3% (25%-75% percentiles:
0.5%-31.8%)
Int: 2.3% (25%-75% percentiles: 0.0%-9.0%)
Control1: 0.5% (25%-75% percentiles:
0.0%-1.8%) NB: Results may be biased by
an outlier
Control2: 0.9% (25%-75% percentiles:
0.0%-3.7%) NB: Only one data point
Int: NR
Control1: NR
Control2:
NR
Norway
Time horizon:
up to 35 days
post op
Discount
rates:
Costs=Not
Applicable
Effects=Not
Applicable
Control1: Dalteparin
28-35 days post op
N: NR
Mean age: NR
M/F:NR
Control2: Warfarin 715 days post op
N: NR
Mean age: NR
M/F:NR
Pre-existing riskfactors:
PE
Confirmed by:
Radiological diagnostics
Control1: Dalteparin
Dose: 5000IU
subcutaneous
Timing: 28-35 days
prophylaxis
Control2: Warfarin
Dose: 5mg
Timing:
7-15 days post op with no
out-patient continuation
Additional noncomparative
prophylaxis:
Fatal PE
NR
Confirmed by:
Bleeding related
complications Major
bleeding defined as "overt
bleeding associated with a
fall in haemoglobin levels
of 2gL^(-1) or more, and
requiring hospitalisation"
Mean cost (In Euros.
Costs included are:
Prophylaxis, Office visit +
Venography, Diagnosis &
Treatment of DVT, PE
treatment, Management of
major bleeding, Autopsy
(50% rate), death
certificates)
Cost-effectiveness: (Cost
per event averted)
Sensitivity analysis:
Deterministic sensitivity
analysis
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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During Hospitalisation
Int: 2.0% Control1: 2.0% Control2:
2.9% Post Discharge
Int: - Control1: 0% Control2: -
Int: €465.151 Control1: €368.013
Control2: €339.397
Long term prophylaxis with Dalteparin averts
about 30 clinical DVTs and 18 PEs, leading
to savings of around €2000 per event
averted.
As compared to Warfarin, Long
term prophylaxis has a ICER of around €900
per event averted (28 DVTs and 4 PEs per
1000 patients)
Varying the prevalence of thromboembolic
events, Long term prophylaxis with
Dalteparin is the best option when upper
Outcomes not
included:
HRQL,
Survival, LOS,
LE
DRAFT FOR CONSULTATION
bound estimations are considered, and is the
worst one, when the lower bound estimations
are used
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
479 of 648
DRAFT FOR CONSULTATION
Bibliographic
reference
Dainty et al,
120
2004
USA
Study Type
Patients
Type of surgery:
Economic
Gynaecological
analysis:
oncological
Costeffectiveness
Model A:
35-year old, stage
Study
1B cervical cancer
design:
Markov
Model B:
model
55-year old, stage
1A endometrial
Time
horizon: NR cancer
Discount
rates:
Costs=3%
Effects (lifeyears)=3%
Model C:
65-year old, stage
3C ovarian cancer
Interventions
Int: Intermittent
pneumatic compression
and enoxaparin Dose:
40mg/day Timing: 5
days
Control: Intermittent
pneumatic compression
only Timing: 5 days
Additional noncomparative
prophylaxis: NR
Outcome measures
Effect size
Comments
Model A:
Int: 2395 Control: 2389
Model B:
Int: 3592 Control: 3583
Model c:
Int: 8380 Control: 7100
Funding: NR
Fatal PEs prevented per
100,000
Model A:
Int: 1806 Control: 1533
Model B:
Int: 2728 Control: 2300
Model c:
Int: 5420 Control: 4600
Other limitations:
1. Results sensitive to the
assumed risk reduction in DVT.
2. There are limited clinical
data on combined prophylaxis.
Mean Cost (US $ 2001
Hospital charges for:
prophylaxis, diagnosis of VTE,
treatment of VTE, post-surgical
treatment of underlying
disease )
Model A:
Int: $1406 control: $1127
Model B:
Int: $1406 control: $1132
Model c:
Int: $39,400 control: $38,900
DVTs prevented per 100,000
Mean Life expectancy (years) Model A:
Int: 21.664 control: 21.637
Model B:
Int: 20.05 control: 20.01
Model c:
Int: 6.754 control: 6.729
Cost-effectiveness:
Converted to £ using PPPs
Sensitivity analysis:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
480 of 648
Model A:
Int vs. control: $10, 091 (£6,287) per
life year gained
Model B:
Int vs. control: $7,150 (£4,454) per
life year gained
Model C:
Int vs. control: $50,181 (£31,263) per
life year gained
Intervention remains cost-effective (i.e.
<$50,000 per life year) f the risk
reduction decreased from 6.4% to at
least 4%.
Outcomes not included:
PTS, mortality due to bleeding
(cost included though), HRQL
Other comments: Markov
model adapted from Maxwell
2000348. See comments on this
study.
Since this is a model, p-values,
etc are NA
DRAFT FOR CONSULTATION
Bibliographic
reference
Davies et al,
122
2000
UK
Study
Type
Patients
Interventions
Economic
analysis:
Costeffectivene
ss
Type of surgery:
Elective hip
replacement
Int: extended
enoxaparin Dose:
40mg/day
Timing: index hospital
admission and 21 days
post-discharge
Study
design:
Decision
analysis
Time
horizon:
Lifetime
Discount
rates:
Costs=1.5
%
Effects
(LYG,
QALY)=1.5
%
Mean age: 70
M/F:NR
Pre-existing risk- Control: standard
enoxaparin Dose:
factors: NR
40mg/day Timing:
index hospital
admission only
Additional noncomparative
prophylaxis: NR
Outcome measures
Effect size
DVT (probability)
Int: 18% Control: 39%
PE (probability)
Int: 0%
Fatal PE 1 hour (probability)
Int: 11%
Survival
Treated and untreated DVT
No DVT
Treated PE
Untreated PE
Int: 99% Control: 99%
Int: 100% Control: 100%
Int: 92% Control: 92%
Int: 70% Control: 70%
Control: 4%
Control: 11%
Mean cost (£ 1997-98, societal
perspective, predominantly NHS
direct costs)
Int: £428.14 Control: £184.24
Life-years (Number of lives
gained multiplied by the average
life expectancy of the cohort. Life
expectancy was estimated to be
81 years)
Int: 10.07 Control: 10.01
Quality-adjusted life-years (age- Int: 7.48 Control: 7.43
specific utility values extracted
from a national survey of healthrelated QOL using EuroQol)
Cost-effectiveness:
Cost/life year gained
Cost/QALY gained
88% of sensitivity analyses estimated
cost/QALY < £7,000.
Results sensitive to:
1. % of patients/carers who could administer
injections at home
2. Rate of PE for both groups
3. Rate of DVT for controls
Highest estimate = £27,000/QALY gained is
rate of PE is assumed to be equal.
Sensitivity analysis:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
£4,257
£5,732
481 of 648
Comments
Funding: Aventis Pharma,
UK
Outcomes not included:
PVT, PTS, Bleeding, LOS
Other limitations:
1. Model used point
estimates from a limited
number of sources.
2. A wide range of
assumptions are used –
authors claim these are
conservative assumptions.
3. Utility values do not
account for difference in
rate of DVT or PE.
Other Comments:
Main clinical data extracted
from Bergqvist 199649.
Since this is a model, pvalues, etc are NA
DRAFT FOR CONSULTATION
Bibliographic
reference
Study Type Patients
characteristics
Dranitsaris et al,
135
2004
Economic
analysis:
Cost
consequenc
es analysis
Canada
Study
design:
Decision
analysis
(based on
established
489
model
Time
horizon:
90 days
Discount
rates:
NA
Type of surgery:
A. Total hip
replacement
Mean age: NR
M/F:NR
B. Total knee
replacement
Mean age: NR
M/F:NR
C. Hip fracture
Mean age: NR
M/F:NR
Pre-existing riskfactors:
NR
Interventions
Outcome measures
Effect size
Comments
Int: Fondaparinux
Dose: NR Timing:
Postop for 7 days
DVTs averted (Intv vs control)
Confirmed by: NR
A. 0.7%
B. 1.3%
C. 1.4%
Funding: Sanofi
Synthelabo Canada Inc
Control: Enoxaparin
Dose: NR Timing:
Postop for 7 days
Additional noncomparative
prophylaxis:
NR
PEs averted (Intv vs control)
Confirmed by: NR
A. 0.4%
B. 0.5%
C. 0.9%
A. Can$40
Mean cost savings (Intv vs
B. Can$58
control)
(2003 Canadian $;
Direct medical costs for prophylaxis, C. Can$81
treatment of PE, DVT, Major
bleeding[sensitivity analysis only])
Cost-effectiveness
Fondaparinux both reduced cost and
prevented VTEs for all three patient
groups
Sensitivity analysis:
Fondaparinux was dominant for all the
alternative scenarios
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
482 of 648
Outcomes not included:
PTS, Bleeding, HRQL,
Survival, LE,
Other comments: Since this
is a model, p-values, etc are
NA
DRAFT FOR CONSULTATION
Bibliographi
c reference
Study Type
Drummond
et al,
136
1994
Economic
analysis: Cost
analysis
UK
Study design:
Simplified
Decision tree
modelling
Time horizon:
short term
(prophylaxis
commenced
before surgery
& continued
until
discharge)
Discount
rates:
Costs=Not
Applicable
Effects=Not
Applicable
Patients
characteristic
s
Type of
surgery:
Elective Hip
Surgery
Intervention:
Enoxaparin
N: NR
Mean age: NR
M/F:NR
Control:
Heparin
N: NR
Mean age: NR
M/F:NR
Interventions
Outcome measures
Effect size
Comments
Int: Enoxaparin
Dose:40mg daily
Timing: Given until
hospital discharge,
starting 12hrs before
surgery
Survival (Expected mortality
per 1000 patients)
Int: 0.5%
Control: 0.9%
p value: NR
Funding: Rhône-Pulenc
Rorer
Control: Heparin
Dose: 5000U at intervals
of 8 hrs
Timing:
Given until hospital
discharge, starting 2hrs
before surgery
Mean cost (1990 £; Costs
included are: Prophylaxis,
Confirming clinical diagnosis,
Additional treatments). Costs
reported as average per
patient over a 1000 patients
population
Int: £104
Control: £124
p value: NR
Additional noncomparative
prophylaxis:
Sensitivity analysis:
Deterministic sensitivity
analysis
Enoxaparin is sensitive only to changes
in cost of administration (could increase
up to £5 per patient)
Outcomes not included:
DVT, PVT, PE, FPE, ,
Post-thrombotic Leg,
Bleeding, HRQL, LOS, LE
Pre-existing
risk-factors:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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DRAFT FOR CONSULTATION
Bibliograp
hic
reference
Study
Type
Eckman et
137
al, 1990
Economic
analysis:
Costeffectivene
ss
USA
Study
design:
Decision
analysis
Time
horizon:
Lifetime
Discount
rates:
Costs=NR
Effects=NR
Patients
Type of
surgery:
Noncardiac
surgery for
patients with
prosthetic
heart valves.
Basecase
analysis:
35 year old
woman
without
substantial
morbidity or
ventricular
dysfunction.
Pre-existing
risk-factors:
NR
Interventions
Intervention: A number of
strategies for treating patients
undergoing surgery to prevent
thromboembolic events were
examined. Costs and events
associated with Incremental use
of heparin therapy and
incremental days required in
hospital for administration of
heparin therapy were modelled.
Outcomes presented:
A: Patients who require
prolongation of
hospitalisation.
Minor ops/values in aortic
position
1. Ball values
2. Bjork-shiley values
3. Lillehei-kaster valves
4. St. Jude
Minor ops/values in mitral
position:
1. Ball values
2. Bjork-shiley values
3. Lillehei-kaster valves
4. St. Jude
B: Patients who require
additional days of heparin,
but not hospitalisation
Major ops/values in aortic
position
1. Ball values
2. Bjork-shiley values
3. Lillehei-kaster valves
4. St. Jude
Major ops/values in mitral
position:
1. Ball values
2. Bjork-shiley values
Outcome measures
Effect size
Comments
Thromboembolism
Events per 100,000 patient-days
Values in aortic position
With anticoagulation 1. 9.2 2. 6.2 3. 6.6 4. 1.3
Without anticoagulation 1. 27.6 2. 18.6 3. 19.8 4.
5.7
Values in mitral position
With anticoagulation 1. 23.8 2. 12.3 3. 11.8 4. 9.9
Without anticoagulation 1. 71.4 2. 36.9 3. 35.4 4.
29.7
Funding:
National
library of
medicine and
John A.
Hartford
Foundation.
Value Thrombosis
Events per 100,000 patient-days
With anticoagulation 1. 0.08 2. 0.90 3. 1.30 4. 0.01
Without anticoagulation 1. 3.62 2. 8.60 3. 9.31 4.
4.49
Values in mitral position
With anticoagulation 1. 1.51 2. 1.92 3. 6.19 4. 0.01
Without anticoagulation 1. 9.59 2. 15.72 3. 28.49
4. 4.49
Survival
Death from embolism %
Values in aortic position
1. 18% 2. 28% 3. 5% 4. 5%
Values in mitral position
1. 13% 2. 18% 3. 24% 4. 5%
Outcomes
not included:
Data on
bleeding,
LOS and LE
are included
in the model
but not
reported
separately for
each strategy.
Mean Cost (US $, year not
reported).Costs included variable costs
only: additional cost of heparin;
additional days required in hospital due
to heparin therapy; additional days
required in hospital due to
thromboembolic events and bleeding
Mean costs were not reported separately for all
strategies.
Ball values in aortic position
0 extra days of hospitalisation – $1428
1 extra days of hospitalisation - $1804
2 extra days of hospitalisation - $2181
3 extra days of hospitalisation - $2558
Quality-adjusted life-years Basecase:
mortality rate=1 per 45 years (0.022/y).
Excess mortality associated with
prosthetic value=0.03/y. Life expectancy
=19.2 years (1/(0.022+0.03).
Adjustments made for each
thromboembolic and bleeding even. LE
multiplied by quality adjustment factors.
QALYs not reported separately for all strategies.
Ball values in aortic position
0 extra days of hospitalisation – 19.1863
1 extra days of hospitalisation – 19.1884
2 extra days of hospitalisation – 19.1894
3 extra days of hospitalisation – 19.1898
Marginal Cost-effectiveness: qualityadjusted life year.
A: Patients who require prolongation of
hospitalisation.
Minor ops/values in aortic position
1. $174,000 (1 extra day), $377,000 (2), $1,130,000
A: For each strategy, data are presented
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
484 of 648
Other
limitations:
Quality
adjustment
factors not
clearly
defined in the
paper.
Other
comments:
Data also
presented for
home
administration
of heparin
therapy –
data not
extracted
here.
DRAFT FOR CONSULTATION
3. Lillehei-kaster valves
4. St. Jude
for the requirement of 1, 2 and 3 extra
days of hospitalisation.
Additional non-comparative
prophylaxis: NR
B: For each strategy, data are presented
for the requirement of 1, 2 and 3 extra
days of heparin therapy.
Cost of thromboembolic events averted
and cost of deaths averted also
presented in paper- data not extracted
here.
To convert to £ multiply by 0.572 (PPP)
Relative risk of thromboembolic events, risk of
severe morbidity and risk of death all varied – costeffectiveness ratios remained high.
Sensitivity analysis:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
(3)
2. $164,000 (1 extra day), $356,000 (2), $1,070,000
(3)
3. $212,000 (1 extra day), $462,000 (2), $1,387,000
(3)
4. $539,000 (1 extra day), $1,169,000 (2),
$3,512,000 (3)
Minor ops/values in mitral position:
1. $75,000 (1 extra day), $162,000 (2), $484,000 (3)
2. $97,000 (1 extra day), $212,000 (2), $635,000 (3)
3. $75,000 (1 extra day), $164,000 (2), $494,000 (3)
4. $227,000 (1 extra day), $494,000 (2), $1,480,000
(3)
B: Patients who require additional days of
heparin, but not hospitalisation
Major ops/values in aortic position
1. $12,200 (1 extra day), $21,000 (2), $64,700 (3)
2. $11,100 (1 extra day), $19,400 (2), $60,900 (3)
3. $14,400 (1 extra day), $25,100 (2), $78,900 (3)
4. 3$8,600 (1 extra day), $65,800 (2), $202,000 (3)
Major ops/values in mitral position:
1. $4,600 (1 extra day), $8,400 (2), $27,200 (3)
2. $5,900 (1 extra day), $10,900 (2), $35,500 (3)
3. $4,100 (1 extra day), $8,000 (2), $27,100 (3)
4. $15,800 (1 extra day), $27,300 (2), $84,600 (3)
485 of 648
Since this is a
model, pvalues, etc
are NA
DRAFT FOR CONSULTATION
Bibliographi
c reference
Study Type
Etchells et
147
al, 1999
Economic
analysis: Cost
analysis
(extendable to
cost
effectiveness)
Canada
Study design:
Decision tree
Time horizon:
Short term
horizon
Discount
rates:
Costs=3%
(only a part of
the analysis
involves
indirect costs,
see Other
comments)
Effects=NR
Patients
characteristic
s
Type of
surgery:
Colorectal
Surgery
Intervention:
Enoxaparin
N: NR
Mean age: 51
yrs
M/F:NR
Control1:
Heparin
N: NR
Mean age: 51
yrs
M/F:NR
Pre-existing
risk-factors:
Interventions
Outcome measures
Effect size
Comments
Int: Enoxaparin Dose:
40mg injected sc, once
daily
Timing: 7
days, starting 2 hrs before
surgery
DVT Confirmed by: NR.
Number of DVTs per 1000
patients
Int: 0.4%
Control: 0.4%
p value: NR
Funding: RhônePoulenc Rorer
Control: Heparin
Dose: 5000U injected sc
3 times daily
Timing:
7 days, starting 2 hrs
before surgery
Additional noncomparative
prophylaxis:
Outcomes not included:
HRQL, Survival, LOS, LE,
Post thrombotic leg, FPE
PE
Confirmed by: NR.
Number of PEs per 1000
patients
Int: 0.5%
Control: 0.5%
p value: NR
Bleeding related
complications (defined as a
decrease in haemoglobin level
of at least 20g/L, or requiring
transfusion of at least 2 units
of red blood cells, or
reoperation)
Mean cost (US$; Costs
include: prophylaxis,
consumables, nursing). Costs
reported as total cost per 1000
patients
Int: 0.27%
Control: 0.15%
p value: NR
Int: $242778
Control: $97111
p value: NR
Cost-effectiveness: (Not
explicitly reported, but
retrievable from data)
Enoxaparin to be dominated; no apparent
clinical benefit, and increase in total costs
Sensitivity analysis:
Deterministic sensitivity
analysis
Model sensitivity tested with respect to
some parameters, but Enoxaparin always to
be Not Cost Effective
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
486 of 648
Other comments:
Indirect costs are reported
from literature under
some assumptions
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Patients
characteristics
Interventions
Outcome measures
Effect size
Comments
Francis et al,
165
1999
Economic
analysis:
Costeffectivene
ss
Type of surgery:
Total hip
replacement
Int: Warfarin Dose:
NR
Timing: NR
DVT (venogram)
Int: 30/192 (15.6%) Control: 49/190 (25.8%)
Funding: Pharmacia &
Upjohn
Bleeding related complications
(haematoma, excessive
intraoperative bleeding, excessive
drainage at the operative site,
haematuria, GI bleeding, urinary
tract bleeding)
Hospital
Int: 16/192 (8.3%) Control: 4/190 (2.1%)
p=0.0098
Follow-up
Int: 6/192 (3.1%) Control: 1/190 (0.5%)
p=0.00012
Mean cost (US$; hospital costs of
prophylaxis and the treatment of
DVT, PE & major bleeding;
macrocosting involved applying a
standard average cost per day for
elective hip patients to the study
LOS; microcosting involved
costing each treatment event
separately)
Microcosting:
Int: $9,330 Control: $9,372 p=NR
Macrocosting:
Int: $11,544 Control: $10,185 p=NR
Cost-effectiveness: (cost per
DVT averted)
Microcosting:
Int vs Control: LMWH dominates
Macrocosting:
Int vs Control: $6509 per DVT averted
Sensitivity analysis (unit costs)
Results were robust to changes in unit costs.
USA
Study
design:
164
RCT
Time
horizon:
5-7 weeks
Discount
rates:
NA
Intervention:
N: 190
Mean age:
63.8±12.9
M/F:95/95
Control:
N: 192
Mean age:
63.1±13.95
M/F:92/100
Pre-existing riskfactors:
53%
cardiovascular
disease
20% trauma to
lower limb
Control: LMWH
Dose: NR Timing:
NR
Additional noncomparative
prophylaxis:
NR
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
487 of 648
Outcomes not included:
DVT PE, FPE, PTS,
Bleeding, HRQL, Survival,
LOS, LE
Limitations:
Cost-effectiveness is
measured in terms of DVT
averted (ignoring the
bleeding events)
DRAFT FOR CONSULTATION
Bibliographic
reference
Friedman et al,
172
2000
USA
Study
Type
Patients
Interventions
Economic
analysis:
Cost
analyses
Type of surgery:
Total hip
arthroplasty
Int: Extended
outpatient prophylaxis
with enoxaparin Dose:
40mg
Timing:
Start on Day 1 after
discharge and
continue for 21 days.
Study
design:
Decision
analysis
Time
horizon:
21 days
postdischarge
Discount
rates: NA
N: NR
Mean age: NR
M/F:NR
Outcome measures
Effect size
DVT risk
Int: 8% (4-12) Control: 10% (2-15)
Proximal DVT risk
Int: 3% (2-5) Control: 5% (2.5-7)
Distal DVT risk
Int: 5% (2.5-7) Control: 5% (2.5-7)
PE
Int: 0% Control: 0.99% (0.50-1.50)
Major bleeding risk
Int: 0% Control: 1.0% (0.50-1.50)
Mean Cost (US $ 1997, drug,
administration, treatment of
failures and complications,
perspective=payer)
Total costs: (homebound – monitoring
provided at home and minimal
prothrombin time monitoring):
Int: $711.36 (£443.89) Control: $700.95
(£437.39)
Pre-existing risk- Control: Extended
prophylaxis with
factors: NR
warfarin Dose: 5mg
Timing: Start on Day 1
Converted to £ using PPPs
after discharge and
continue for 21 days.
Additional noncomparative
prophylaxis: NR
Total costs (ambulatory – outpatient
monitoring and minimal prothrombin time
monitoring):
Int: $532.54 (£332.30) Control: $519.41
(£324.11)
Results sensitive to the extent of monitoring
required for warfarin.
Sensitivity analysis:
Comments
Funding: NR
Outcomes not included:
PTS, HRQL, Survival, LOS,
LE.
Other limitations:
1. Costs based on charges
rather than actual costs.
2. Costs limited to drug,
administration,
complications and failures
from a payer perspective
only.
3. Risk based on clinical
trial data – may not
represent clinical
experience.
4. Costs sensitive to extent
of warfarin monitoring
assumed.
Other comments: Since
this is a model, p-values,
etc are NA
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
488 of 648
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Gordois et al,
190
2003
Economic
analysis:
Cost
consequen
ces
analysis
UK
Patients
characteristics
Type of surgery:
A. Total hip
replacement
Mean age: NR
M/F:NR
B. Total knee
replacement
Mean age: NR
Study
M/F:NR
design:
C. Hip fracture
Decision
Mean age: NR
analysis
M/F:NR
(based on
established Pre-existing risk489
factors:
model
NR
Time
horizon:
5 years
(also one
year,
90days, 30
days and
discharge –
data not
extracted)
Interventions
Outcome measures
Effect size
Comments
Int: Fondaparinux
Dose: 2.5mg once
daily Timing: Postop
for 7 days
Clinical VTE
A, B and C combined
Day 30. Int: 2.1% Control: 3.6%
5 years. Int: 3.3% Control: 5.3%
Funding: Sanofi
Synthelabo
Fatal PE
A, B and C combined
Day 30. Int: 0.3% Control: 0.5%
5 years. Int: 0.4% Control: 0.7%
Control: Enoxaparin
Dose: 40mg once
daily Timing: Postop
for 7 days
Additional noncomparative
prophylaxis:
NR
Day 30. Int: £130 Control: £130
Mean Cost (2000-2 UK£; Direct
5 years. Int: £219 Control: £246
medical costs for prophylaxis,
treatment of PE, DVT, recurrence,
PTS, Major bleeding, false
positives)
A, B and C combined
Cost-effectiveness: (cost per
death averted)
A, B and C combined
Day 30. Int vs Control: Fondaparinux
dominates
5 years. Int vs Control: Fondaparinux
dominates
Sensitivity analysis: (various
parameters were subjected to
onew-way sensitivity analysis)
Fondaparinux ceased to be cost saving if
enoxaparin cost less than £2.13 per day or if
the rate of late DVT is increased 50% over
Enoxaparin.
Discount
rates:
NA
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
489 of 648
Other comments: Since
this is a model, p-values,
etc are NA
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Patients
characteristics
Interventions
Outcome measures
Effect size
Comments
Gozzard et al,
195
2004
Economic
analysis:
Costeffectivene
ss analysis
Type of surgery:
Curative surgery
for abdominal
cancer
1: Extended
enoxaparin Dose:
40mg once daily
Timing: Postop for 29
days
DVT
1: 0.8% 2: 2.1% 3: 2.6%
Funding: Sanofi
Synthelabo
Symptomatic PE
1: 0.1% 2: 0.3% 3: 0.4%
Major bleeding
1: 4.0% 2: 4.0% 3: 2.8%
2: Enoxaparin
Dose: 40mg once
daily Timing: Postop
for 7 days
Mean life-years lost
1: 0.8 2: 2.0 3: 2.5
Mean Cost (2001-2 UK£; health
care costs of prophylaxis and
treatment of VTE and major
bleeding)
1: £462 2: £186 3: £202
Sensitivity analysis: (various
parameters were subjected to
one-way sensitivity analysis)
Most analyses pushed the cost-effectiveness
of extended enoxaparin use above £20,000
per life-year. When the lower 95%
confidence limit for extended prophylaxis was
used, the cost-effectiveness leapt to
£149,000 per life-year gained.
UK
Study
design:
Decision
analysis
Time
horizon:
NR
Discount
rates:
NR
Hypothetical
cohort
3: UFH
Dose: 5000IU 3 times
daily Timing: Postop Cost-effectiveness: (cost per life- 2 vs 3: Enoxaparin dominates
year gained)
1 vs 2: £22,700 per life-year gained
for 8 days
Additional noncomparative
prophylaxis:
NR
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
490 of 648
Other comments: Since
this is a model, p-values,
etc are NA
DRAFT FOR CONSULTATION
Bibliographic
reference
Haentjens et
203
al, 2004
Study Type
Economic
analysis: Cost
utility
Belgium
Study design:
Decision tree
analysis
Time horizon:
1 year
Discount
rates:
Costs=Not
Applicable
Effects=Not
Applicable
Patients
Interventions
characteristics
Type of
Int: LMWH Dose: NR
surgery:
Timing: 12 days post ops
Total Hip or
Knee
Control: LMWH Dose:
Replacement
NR
Timing: 42 days
post ops
Intervention:
Low Molecular
Additional nonWeight
comparative
Heparins short
prophylaxis:
term
prophylaxis
N: NR
Mean age: NR
M/F:NR
Control: Low
Molecular
Weight
Heparins long
term
prophylaxis
N: NR
Mean age: NR
M/F:NR
Pre-existing
risk-factors:
Outcome measures
DVT Confirmed by: NR
PE
Confirmed by: NR
Bleeding related
complications (as defined by
a fall in the haemoglobin
concentration by at least
2.0g/dl, or gastrointestinal,
intracranial or retroperitoneal
bleeding
Mean cost (2001 Euros. Cost
included: Thomboembolitic
prophylaxis; Diagnosis &
Treatment of DVT, PE,
Bleeding)
Quality-adjusted life-years
(Measured on the utility over
health status, defined in cited
study)
Effect size
Distal DVT
Total Hip Replacement (probability)
Int: 0.149 Control: 0.103 p value: NR
Total Knee Replacement (probability)
Int: 0.347 Control: 0.354 p value: NR
Proximal DVT
Total Hip Replacement (probability)
Int: 0.205 Control: 0.115 p value: NR
Total Knee Replacement (probability)
Int: 0.149 Control: 0.126 p value: NR
Int: 0.0150
Control: 0.0150 p
value: NR
Total Hip Replacement (probability)
Int: 0.017 Control: 0.017 p value: NR
Total Knee Replacement (probability)
Int: 0.005 Control: 0.005 p value: NR
Total Hip Replacement (probability)
Int: €320 Control: €378 p value: NR
Total Knee Replacement (probability)
Int: €287 Control: €401 p value: NR
Cost-effectiveness:
(Incremental cost utility ratio)
Total Hip Replacement (probability)
Int: 0.9766 Control: 0.9849 p value:
NR
Total Knee Replacement
(probability)
Int:
0.9774 Control: 0.9791 p value: NR
Prolonged prophylaxis has a ICUR of
€6964 for THR, and of €64907 for TKR
Sensitivity analysis:
Deterministic sensitivity
Confirms the results for the base case
scenario
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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Comments
Funding: Aventis
Pharma
Outcomes not included:
FPE, Thrombotic Leg,
HRQL, Survival, LOS, LE
DRAFT FOR CONSULTATION
analysis
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
492 of 648
DRAFT FOR CONSULTATION
Bibliographic
reference
Study Type
Patients
characteristics
Interventions
Outcome measures
Effect size
Comments
Hawkins et al,
217
1998
Economic
analysis:
Cost
effectiveness
analysis
Type of surgery:
Knee
Replacement
Int: Enoxaparin
Dose: 30mg
Timing: 4 days
Control: Warfarin
Dose: 5mg
Timing: 4 days
a) Int: 0.117
Control: 0.104
p
value: NR
b) Int: 0.252
Control: 0.413
p
value: NR
c) Int: 0.369
Control: 0.517
p
value: NR
Int: 0.03
Control: 0.09
p value:
NR
Funding: Rhône-Poulenc
Rorer
Intervention:
Enoxaparin
N: NR
Mean age: NR
M/F:NR
DVT Confirmed by:
Ultrasonography:
a)
Proximal DVTs
b) Distal DVTs
c) All DVTs
USA
Study
design:
Decision
Analytic
Model
Time
horizon: NR
Discount
rates:
Costs=NR
Effects =NR
Control:
Warfarin
N: NR
Mean age: NR
M/F:NR
Pre-existing
risk-factors:
NR
Additional noncomparative
prophylaxis:
PE
Confirmed by: NR
Bleeding related
complications (generically
defined as "major bleeding")
Int: 0.021
NR
Mean cost (US$, year NR.
Costs included are:
Prophylaxis; Diagnosis &
Treatment of Proximal DVT;
Diagnosis & Treatment of
Distal DVT; False Positive
DVT; PE; Major Bleed)
Cost-effectiveness: (Cost
per DVT averted, Cost per
PE averted)
Sensitivity analysis:
Univariate Deterministic
sensitivity analysis
Int: $1865
value: NR
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
493 of 648
Control: 0.018
Control: $1743
p value:
p
Enoxaparin produces a cost per event of
DVT averted of $2525, and a cost per
event of PE averted of $87201
Tends to confirm the results in terms of
cost-effectiveness
Outcomes not included:
HRQL, Survival, LOS, LE
DRAFT FOR CONSULTATION
Bibliographic
reference
Study Type
Patients
Heaton and
218
Pearce, 1995
Economic
analysis:
Cost
consequence
Type of
surgery:
1. General
surgery
(abdominothora
cic or
gynaecological).
New Zealand
Study
design:
Cohort clinical data
derived from
a metaanalysis
(Nurmohame
d 1992)
Time
horizon: NR
Discount
rates: NA
Intervention:
N:1137
Mean age: NR
M/F:NR
Control:
N:1127
Mean age: NR
M/F:NR
2. Orthopaedic
surgery
(elective or
traumatic hip
surgery)
Pre-existing
risk-factors:
Interventions
1. General Surgery
Int: Low molecular
weight heparin Dose:
Dalteparin 2500U daily,
or Enoxaparin 1600U
(20mg) daily, or
Tinzaparin 2500U daily
Timing: 7 days
Outcome measures
DVT Confirmed by:NR
1. Int: 6.68% Control: 7.36%
2. Int: 17.31% Control: 25.22%
Comments
Funding: NR
Outcomes not included:
PTS, Bleeding, HRQL,
Survival, LOS, LE.
PE
Confirmed by:NR
Control: Unfractionated
heparin Dose: Heparin
5000U q12h Timing: NR Cost ($ NZ, year not specified,
Cost of treating DVT and PE)
2. Orthopaedic Surgery Converted to £ using PPPs
Int: Low molecular
weight heparin Dose:
Dalteparin 5000U daily,
or Enoxaparin 3200U
(40mg) daily, or
Cost-effectiveness:
Tinzaparin 4500U daily
Timing: 7 days
Control: Unfractionated
heparin Dose: Heparin
5000U q8h Timing: NR
Effect size
Sensitivity analysis:
Additional noncomparative
prophylaxis: NR
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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1. Int: 6.68% Control: 7.36%
2. Int: 17.31% Control: 25.22%
1. Int: $285 (£122) Control: $305 (£130)
2. Int: $806 (£344) Control: $1,128 (£482)
NR
NR
Other limitations:
1. Data limited to cost of
treating DVT and PE.
2. No sensitivity analysis,
no statistical analyses.
Other comments: The
paper also presents data
on cost analysis of
treatment of established
DVT with LWMH vs. UFH
and applying local costs.
Data not extracted here.
DRAFT FOR CONSULTATION
Bibliographic
reference
Heerey and
221
Suri, 2005
Study
Type
Patients
Interventions
Economic
analysis:
CUA
Type of surgery:
Int: Dalteparin
Dose: 5000U
Timing: every 24
hours 10 days
(treatment start 2
hours before surgery)
USA
Study
design:,
Decision
analysis
Abdominal
Surgery
Outcome measures
Total costs, 15 years, Swedish
costs inflated according to a
parameter to US$
Life years (y), 15 years
Interventions:
Dalteparin 5000U
Time
horizon:
Daltparin 2500U
15 years
UFH 5000U
N: cohort of 50000
Discount
Mean age: 69
rates:
Costs and M/F:50%/50%
utilities=3%
annum
Pre-existing riskfactors:
Proximal DVT,
Distal DVT,
PE
Death due to VTE
Death following
VTE
Major bleeding
during VTE
prophylaxis
Severe postphlebitic
syndrome
Recurrent VTE
Effect size
UFH: 45855 $ DPH2500U: 45882 $
DPH5000U: 46308 $
Funding : no sources of
funding
UFH: 12.08 DPH2500U: 12.09
Outcomes not included:
DVT, PE, MB
DPH5000: 12.11
Int: Dalteparin
Dose: 2500U
Timing: every 24
hours 10 days
(treatment start 2
hours before surgery)
Int: UFH
Dose: 5000U
Timing: every 12
hours 10 days
(treatment start 2
hours before surgery)
QALYs, 15 years
ICER for cost per/YOL saved
($US)
ICER for cost per QALY gained
($US)
Additional noncomparative
prophylaxis:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
495 of 648
Comments
Other limitations: The
authors have used similar
UFH: 9.56 DPH2500U: 9.56 , DPH5000U: estimates for all three
9.58
interventions for the longDPH2500 vs UFH: 4754 ; DPH5000 vs UFH: term complications
occurring in those who
17843 ; DPH5000 vs DPH2500: 21959;
experienced VTE in the first
DPH2500 vs UFH: 9310 ; DPH5000 vs UFH: 30 days.;
21779 ; DPH5000 vs DPH2500: 23799 ;
They have not explicitly
evaluated the impact of
intracranial haemorrhage
as a result of these
preventive interventions. ;
they have not analysed
certain high-risk patient
populations (e.g patients
with malignancy or
thrombophylia), who carry
higher risk of VTE
DRAFT FOR CONSULTATION
Bibliographic
reference
Study Type
Patients
characteristics
Interventions
Outcome measures
Effect size
Comments
Hodge,
231
1991
Economic
analysis:
Costconsequences
analysis
Type of surgery:
Total knee
arthroplasty
(Duration of
surgery=NR)
Intervention:
N: 66
Mean age: NR
M/F:23/43
Int: 31% Control: 33% p value: NR
(seems to be as a proportion of operated
knees)
Int: 6% Control: 6% p value: NR
(seems to be as a proportion of operated
knees)
Int: 0 Control: 0
Time
horizon: 8-10
days post-op
Control:
N: 35
Mean age: NR
M/F:8/27
Control: Warfarin Dose:
Initial 10mg then maintain
thrombin time between 1.3
and 1.5 Timing: Day
before surgery until
discharge
DVT Confirmed by:
bilateral lower extremity
venogram
PVT Confirmed by:
bilateral lower extremity
venogram
PE
Confirmed by:
clinical signs
Cost (administration of
treatment - hospital costs
excluding physician time)
Funding: NR
Study
design:
Cohort
analysis
Int: Pneumatic calf
compression (PCC) boot
Details: Sequential
pressures were kept
between 35 and 55 mmHg
Timing: During surgery
(opposite leg) and then
both legs until discharge
Sensitivity analysis:
NR
Pre-existing riskfactors:
NR
Additional noncomparative prophylaxis:
NR
USA
Discount
rates:
NA
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
496 of 648
Cost of PCC boot was approximately
50% of warfarin
Outcomes not
included: Physican
time, PTS, Bleeding,
HRQL, Survival, LE
Other limitations:
Costing methods not
described
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Patients
characteristics
Interventions
Outcome measures
Effect size
Comments
Hull et al,
251
1997
Economic
analysis:
Cost
consequen
ces
Type of surgery:
A. Hip
replacement
N: 795
Int: LMWH
(Tinzaparin) Dose:
75 anti-factor Xa U per
kg Timing: postop 9
days
DVT Confirmed by: bilateral
ascending radio-contrast
venography
A. Int: 21% Control: 23% p value: NR
B. Int: 45% Control: 55% p value: NR
PVT Confirmed by: bilateral
ascending radio-contrast
venography
A. Int: 5% Control: 4% p value: NR
B. Int: 8% Control: 12% p value: NR
Funding: Heart and
Stroke Foundation of
Alberta. Novo Nordisk.
DuPont Pharma
Bleeding related complications
(a decrease in haemoglobin level
of at least 20g/L)
A. Int: 3% Control: 2% p value: NR
B. Int: 3% Control: 1% p value: NR
Mean cost (1992 Canadian
dollars; direct medical costs of
prophylaxis and treatment of
DVTs and bleeding)
A. Int: 4398 Control: 5933 p value: NR
B. Int: 4803 Control: 5688 p value: NR
Cost-effectiveness:
A. Int was cost saving and clinical outcomes
similar
B. Int was cost saving and DVTs were
reduced
Sensitivity analysis: only
conducted for the unit costs and
length of stay
Results were most sensitive to the cost of
bleeding, monitoring INR and drug cost.
Statistical comparisons were not presented.
Canada
Study
design:
244
RCT
Time
horizon:
NR
Discount
rates:
NA
B. Knee
replacement
N:641
Mean age: NR
M/F:NR
Control: Warfarin
Dose: adjusted to
stabilise INR between
2.0 and 3.0 Timing:
postop 9 days
Pre-existing risk- Additional noncomparative
factors:
prophylaxis:
NR
NR
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Outcomes not included:
PE, FPE, PTS, HRQL,
Survival, LOS, LE
DRAFT FOR CONSULTATION
Bibliographic
reference
Study Type
Hull et al,
245
1982
Economic
analysis:
Cost analysis
Canada
Study
design:
simple model
using cohort &
literature
review
Time
horizon: NR:
<12 months
Discount
rates:
NA
Patients
characteristic
s
Type of
surgery:
Abdominothor
acic (>30
minutes; GA;
70% were
gallbladder,
stomach or
large bowel)
N: 1042
Mean age: NR
M/F:NR
Pre-existing
risk-factors:
15% had
cancer
age>40
Interventions
Outcome measures
Effect size
Comments
1: IPC Details: NR
Timing: for 7 days postop
DVT
NR
Fatal PE
1: NR 2: 0.1% 3: 0.1% 4: NR 5: 0.8%
Mean cost (1982
Canadian$; prophylaxis,
diagnosis & treatment of
VTE)
Cost-effectiveness:
1: 53 2: 40 3: 135 4: 350 5: 73
Funding: Province of
Ontario and the Canadian
and Ontario Heart
Foundations
Sensitivity analysis:
NIL was dominated in all scenarios. 1
and 2 were the lowest cost strategies in
each scenario.
2: LDUH Dose: 5000U
Timing: 2 hours preop and
every 8 hours for 7 days
postop
3: Dextran Dose:1.5l on
1st day then 500ml daily
for 3 days postop
4: Surveillance using
iodine-125 labelled
fibrinogen Details:NR
Timing: for 7 days postop
5: NIL
Additional noncomparative prophylaxis:
Early ambulation
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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2 dominates 3 and 5
Outcomes not included:
PTS, Bleeding, HRQL,
Survival, LE
Other comments: Since
this is a model, p-values,
etc are NA
DRAFT FOR CONSULTATION
Bibliographic
reference
Hye et al,
255
1990
USA
Study
Type
Patients
Patient group: All
patients who had
undergone
placement of
Greenfield vena
Study
cava filters at one
design:
Retrospecti hospital.
ve
Economic
analysis:
CA
Time
horizon:
25 months
mean time
to follow-up
Intervention:
N:121
Mean age: 51
M/F:87/34
Discount
rates: NR
Control:
N:48
Mean age: 49
M/F:28/20
Interventions
Outcome measures
Effect size
Int: Percutaneous
placement of
Greenfield vena cava
filter.
Successful placements
Int: 99% Control: 94%
Bleeding related complications
(post-procedural hematoma,
bleeding)
Int: 6% Control: 2%
Control: Surgical
placement of
Greenfield vena cava
filter.
Femoral vein thrombosis/leg
edema
Int: 4 patients Control: 0
PE
Int: 1 patient Control: 0
Mean Cost (US $, year not
specified, cost includes cost of
product and cost of
administration)
Int: $2744 (£1679) Control: $4699 (£2876)
Additional noncomparative
prophylaxis:
Converted to £ using PPPs
NR
Sensitivity analysis:
Pre-existing riskfactors: Patients
had trauma (20%),
Malignancy (7%),
neurologic
disease (4%),
pulmonary
hypertension
(59%), other
disease (10%).
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Comments
Funding: NR
Outcomes not included:
DVT FPE, PTS, Bleeding,
HRQL, Survival, LOS, LE.
Other limitations:
1. Non-controlled, nonrandomised, therefore
inherent bias.
2. Short period of follow-up
for complications to appear.
3. Costs data limited,
source of cost data not
given.
DRAFT FOR CONSULTATION
Bibliographi
c reference
Study Type
Lloyd et al,
330
1997
Economic
analysis: Cost
analysis
Italy
Study design:
Decision Tree
modelling
Time horizon:
Discount
rates:
Costs=Not
Applicable
Effects=Not
Applicable
Patients
characteristic
s
Type of
surgery:
General or
Orthopaedic
Surgery
Intervention:
Low Molecular
Weight
Heparins
N: NR
Mean age: NR
M/F:NR
Control:
Unfractionated
Heparins
N: NR
Mean age: NR
M/F:NR
Interventions
Outcome measures
Effect size
Comments
Int: LMWH Nandroparin
Dose: 0.3ml daily
Timing:
General Surgery: 6 days
post ops
Orthopaedic Surgery: 8
days
DVT Confirmed by:
Venography
Reported as number of
occurrence per 1000 patients
simulated
General Surgery
Int: 1.9%
Control: 2.4%
p value: NR
Funding: Sanofi
Winthrop and Italfarmaco
Control: UHF
Dose: 5000 units thrice a
day
Timing:
General Surgery: 6 days
post ops
Orthopaedic Surgery: 8
days
Orthopaedic Surgery
Int: 4.8%
Control: 7.4%
p value: NR
PE
Confirmed by: ECGs
and chest x-rays
Reported as number of
occurrence per 1000 patients
simulated. Divided in
submassive & massive PEs
Additional noncomparative
prophylaxis: Warfarin
Pre-existing
risk-factors:
Mean cost (1994 Italian Lire.
Costs included are:
Prophylaxis for both General
and Orthopaedic Surgery,
Investigation of suspected
DVTs, Treatment of DVTs,
Investigation of suspected
PEs, Treatment of PEs)
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SUBMASSIVE PEs
General Surgery
Int: 0.2%
Control: 0.5%
p value: NR
Orthopaedic Surgery
Int: 3.1%
Control: 1.3%
p value: NR
MASSIVE PEs
General Surgery
Int: 0.1%
Control: 0.2%
p value: NR
Orthopaedic Surgery
Int: 0.4%
Control: 1.0%
p value: NR
General Surgery
Int: ITL135048 (£47)
Control: ITL180636 (£63)
p value: NR
Orthopaedic Surgery
Int: ITL362405 (£127)
Control: ITL629632 (£221)
p value: NR
Outcomes not included:
PVT, FPE, HRQL,
Survival, LOS, LE, Postthrombotic leg, Bleeding
DRAFT FOR CONSULTATION
Sensitivity analysis:
Scenario Analysis (13 different
assumptions tested)
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The results are robust to variations in key
assumptions
DRAFT FOR CONSULTATION
Bibliographic
reference
Lundkvist et al,
336
2003
Sweden
Study
Type
Patients
Economic
analysis:
Costeffectivene
ss
Type of surgery:
1. Total hip
replacement
Mean age: NR
M/F:NR
2. Total knee
Study
replacement
design:
Mean age: NR
Decision
M/F:NR
analysis
3. Hip fracture
based on
established Mean age: NR
M/F:NR
model
Pre-existing risk(Sullivan
factors:
2003)
NR
Time
horizon:
5 years
Discount
rates:
Costs=3%
Effects=NR
Interventions
Int: Fondaparinux
Dose: 2.5mg daily
Timing: 7 days
Control: Enoxaparin
Dose: 40mg daily
Timing: 7 days
Additional noncomparative
prophylaxis:
NR
Outcome measures
Effect size
Comments
Clinical DVT Confirmed by: NR
1. Int: 1.84% Control: 2.71%
2. Int: 1.49% Control: 2.73%
3. Int: 3.25% Control: 4.60%
Funding: Sanofi Synthelabo
AB, Sweden
Clinical PE Confirmed by: NR
1. Int: 0.58% Control: 1.09%
2. Int: 0.66% Control: 1.19%
3. Int: 0.99% Control: 1.85%
Survival (VTE-related deaths)
1. Int: 0.11% Control: 0.19%
2. Int: 0.12% Control: 0.20%
3. Int: 0.73% Control: 1.34%
Outcomes not included:
PTS, major bleeds, LOS were
included in the model but no
comparative rates were
presented in the paper. No
data on HRQL or LE.
Cost (Euro, 2002, Direct medical
costs for prophylaxis, treatment of
PE, DVT, recurrence, PTS, Major
bleeding, False positives)
1. Int: €268.7 Control: €265.4
2. Int: €272.9 Control: €312.0
3. Int: €365.2 Control: €443.3
Cost-effectiveness: (cost per
VTE prevented)
1. €239 per VTE prevented (£146)
2. Dominated
3. Dominated
Converted to £ using historical
exchange rate
Sensitivity analysis: (Cost after
HF, % DVT patients treated inhospital, rate of major bleeds, risk
reduction assumed for
fondaparinux, cost of
fondaparinux)
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1.Cost-effectiveness remained below €4,100
in all scenarios
2. Dominated in all scenarios except an
assumed risk reduction of 27% for
fondaparinux (€778 per VTE prevented)
3. Dominated in all scenarios
Other comments:
See Gordois 2003190 for the
UK version of this comparison
using the same model.
Since this is a model, pvalues, etc are NA
DRAFT FOR CONSULTATION
Bibliographic
reference
Mamdani et
339
al, 1996
USA
Study Type
Economic
analysis:
Costeffectiveness
analysis
Study
design:
Decision
analysis
Time
horizon: NR
Discount
rates:
Costs=5%
Effects=NA
Patients
characteristics
Type of surgery:
Elective
abdominal
surgery (General
anaesthesia;
requiring at least 5
days of
hospitalisation;
Duration of
surgery>30
minutes)
Mean age: NR
M/F:NR
Pre-existing riskfactors:
age>40 and 'at
least moderate
risk'
Interventions
Outcome measures
Effect size
Comments
1: IPC Details: 2
ambulations per day
Duration: 4 days
DVT
1: 0.75% 2: 0.58% 3: 0.42% 4: 3.50%
Funding: NR
PE
1: 0.60% 2: 0.58% 3: 0.42% 4: 1.20%
Bleeding related
complications Additional
major bleeds
Deaths
1: 0 2: 0.63% 3: 0.53% 4: 0
Outcomes not
included: PTS,
HRQL, LE
2: LDUH Dose: 5000U bid
Duration: 6 days
3: LMWH (Dalteparin) Dose:
2500U qid Timing: 6 days
1: 0.30% 2: 0.16% 3: 0.27% 4: 0.62%
4: NIL
Mean Cost (1996 US$,
Direct medical costs)
1: $102 2: $84 3: $122 4: $112
Additional non-comparative
prophylaxis:
NR
Cost-effectiveness: (cost
per life saved)
NIL is dominated by all prophylaxis
interventions. 2 dominates both 1 and 3
Sensitivity analysis:
Results were sensitive to the relative
effectiveness of the different
interventions and the cost of DVT
treatment (where either IPC or NIL
became optimal)
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Other comments:
Since this is a
model, p-values,
etc are NA
DRAFT FOR CONSULTATION
Bibliographi
c reference
Study Type
Marchetti et
343
al, 1999
Economic
analysis: Cost
effectiveness
analysis
Italy
Study design:
Decision tree
analysis
Time horizon:
3 years post
op
Discount
rates:
Costs=3%
Effects
(QALE)=3%
Patients
characteristic
s
Type of
surgery:
Total Hip
Replacement
Interventions
Outcome measures
Effect size
Int: LMWH Dose: NR
Timing: restricted (2
weeks post op) and
prolonged (4 weeks post
op)
Mean cost (1998 US$; Cost
included are: Prophylaxis,
Ultrasonography,
Phlebography, Treatment,
Stroke, Bleeding)
Int: $2208
value: NR
Quality-adjusted life-years
(Adjustment for disability after
haemorragic stroke &
discomfort of the postthromboembolitic syndrome.
RESULTS REPORTED IN
TERMS OF QALE SAVED)
Int: 13.40yrs
p value: NR
Control:
Unfractionated
Heparins
Cost-effectiveness:
(Measured as Cost per QALE
in days)
LMWH saved $3.12 per QALE in days
N: NR
Mean age: 67
M/F:NR
Sensitivity analysis:
Deterministic Analysis
Model proved relatively robust, upon
varying the parameters
Intervention:
Low Molecular
Weight
Heparins
N: NR
Mean age: 67
M/F:NR
Control: UH Dose: NR
Timing: restricted (2
weeks post op) and
prolonged (4 weeks post
op)
Additional noncomparative
prophylaxis:
Pre-existing
risk-factors:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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Comments
Control: $2283
p
Funding: NR
Outcomes not included:
DVT, PVT, PE, FPE,
Survival, LOS, LE
Control: 13.33yrs
DRAFT FOR CONSULTATION
Bibliographic
reference
Study Type
Patients
characteristics
Interventions
Outcome measures
Effect size
Comments
Maxwell et al,
348
2000
Economic
analysis: Costeffectiveness
analysis
Type of surgery:
Gyneacological
oncological
1: IPC Details: NR
Duration: 5 days
DVTs prevented
Model A
1 vs 4: NR 2 vs 4: 2.45% 3 vs 4: 2.45%
Model B
1 vs 4: 4.97% 2 vs 4: 4.90% 3 vs 4: 4.90%
Model C
1 vs 4: 9.94% 2 vs 4: 9.80% 3 vs 4: 9.80%
Funding: NR
USA
Study design:
Markov model
Time horizon:
NR
Discount rates:
Costs=3%
Effects (lifeyears)=3%
Model A:
35-year old, stage
1B cervical cancer
Model B:
55-year old, stage
1A endometrial
cancer
Model C:
65-year old, stage
3C ovarian cancer
2: LDUH Dose: 5000
units every 8 hours
Duration: 5 days
3: LMWH Dose:
40mg daily Duration:
5 days
Fatal PEs prevented
4: NIL
Additional noncomparative
prophylaxis: NR
Mean cost (1998 US$,
Hospital charges for:
prophylaxis, diagnosis of
VTE, treatment of VTE,
post-surgical treatment
of underlying disease)
Mean life expectancy
(years)
Cost-effectiveness:
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Model A
1 vs 4: 0.66% 2 vs 4: 0.65% 3 vs 4: 0.65%
Model B
1 vs 4: 1.32% 2 vs 4: 1.30% 3 vs 4: 1.30%
Model C
1 vs 4: 2.64% 2 vs 4: 2.60% 3 vs 4: 2.60%
Model A
1: $2912 2: $3069 3: $3084 4: $2866
Model B
1: $973 2: $1123 3: $1140 4: $965
Model C
1: $32,899 2: $33,026 3: $33,042 4:
$31,955
Model A
1: 22.449 2: 22.446 3: 22.446 4: 22.226
Model B
1: 20.281 2: 20.278 3: 20.278 4: 20.012
Model C
1: 6.810 2: 6.807 3: 6.807 4: 6.628
Model A
2 and 3 are dominated by 1.
1 vs 4: $207 per life-year gained
Model B
2 and 3 are dominated by 1.
1 vs 4: $27 per life-year gained
Model C
2 and 3 are dominated by 1.
1 vs 4: $5132 per life-year gained
Outcomes not
included:
PTS, mortality due
to bleeding (cost
included though),
HRQL
Other limitations:
There seems to be a
contradiction in their
reporting of Model A
(Have sought
clarification from
authors).
Other comments:
Since this is a
model, p-values, etc
are NA
DRAFT FOR CONSULTATION
Sensitivity analysis:
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LMWH is most cost-effective (<$50,000 per
life-year) if the risk reduction is:
Model A: 72%, Model B: 71%, Model C:
70%
DRAFT FOR CONSULTATION
Bibliographic
reference
McInnes et al,
354
1992
USA
Study
Type
Patients
Interventions
Economic
analysis:
Cost
consequen
ce
Type of surgery:
Total knee
Arthroplasty –
patients had
osteoarthritis or
rheumatoid
arthritis.
Int: Continuous
passive motion plus
standardized
rehabilitation
programme Timing:
Start within 24 hours of
surgery. Range
increased as tolerated.
Patients instructed to
use as much as
possible.
Study
design:
RCT
Time
horizon: 6
weeks
Discount
rates: NR
Intervention:
N:51
Mean age:
65.7±1.6
M/F:35%/65%
Drop-outs:3
Control:
N:51
Mean age:
70.2±1.3
M/F:36%/64%
Drop-outs:6
Outcome measures
Effect size
DVT
Int: 2% Control: 0% p value: Not sig
Length of Hospital Stay (days)
Int: 10.1 Control: 10.3 p value: 0.72
Mean Cost (US $, year not
specified, costs include staff time
for rehab, equipment, cost of
manipulation)
Converted to £ using PPPs
Int: $1,181 (£720) Control: $1,362 (£830)
Other measure of effect: Range
of motion and function
outcomes
Use of CPM increased active flexion and
decreased swelling, but did not affect pain,
active and passive extension or quadriceps
strength
Control: Standardized
Sensitivity analysis:
rehabilitation
programme Timing:
Start on 1st post-op
day
NR
Additional noncomparative
prophylaxis: NR
Pre-existing riskfactors: NR
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Comments
Funding: NR
Outcomes not included:
PE, FPE, PTS, Bleeding,
HRQL, Survival, LE.
Other limitations:
1. Limited clinical VTE
data, no costs relating to
treatment of VTE.
2. Costs limited to cost of
intervention and cost of
manipulation.
3. No statistical or
sensitivity analysis on cost
data.
DRAFT FOR CONSULTATION
Bibliographic reference
Menzin et al, 1995
USA
361
Study
Type
Patients
characteristic
s
Interventions
Outcome measures
Effect size
Comments
Economic
analysis:
Cost
effectivene
ss analysis
Type of
surgery:
Total Hip
Replacement
Int: Enoxaparin Dose:
30mg twice daily Timing: NR
DVT Confirmed by: Ultrasound
Results on a simulated cohort of
10000 patients
Int: 252
Control1: 417
Control2: 979
Funding: RhônePoulenc Rorer
PE
Confirmed by: NR
Risk of PE in patients with
undetected DVT
Results on a simulated cohort of
10000 patients
Fatal PE
Confirmed by: NR
Results on a simulated cohort of
10000 patients
Int: 56
Control1: 92
Control2: 217
Outcomes not
included: PTS,
Bleeding, HRQL,
Survival, LOS, LE
Mean cost (US$, 1993. Costs
included are: Prophylaxis, 8days
regime; Confirming clinical diagnosis
of DVT; treating DVT; confirming a
PE; treating a PE)
Cost-effectiveness: (Cost per
Additional Death Averted)
Int: $378.74
Control1:
$325.90
Control2:
$532.70
Study
design:
Decision
Analytic
Model
Time
horizon:
NR
Discount
rates:
Costs=NR
Effects=NR
Intervention:
Enoxaparin
N: NR
Mean age: NR
M/F:NR
Control1:
Warfarin
N: NR
Mean age: NR
M/F:NR
Control2: No
prophylaxis
N: NR
Mean age: NR
M/F:NR
Control1: Warfarin Dose:
adjusted to maintain PT at 14
to 16 seconds, the PT ratio at
1.2 to 1.5, or the international
normalised ratio between 2
and 3 Timing: NR
Control2: No prophylaxis
Dose:
NA
Timing:
NA
Additional non-comparative
prophylaxis:
Sensitivity analysis: Deterministic
univariate sensitivity analysis
Pre-existing
risk-factors:
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Int: 67
Control1: 110
Control2: 259
Warfarin dominated
prophylaxis, and Enoxaparin
has a cost of $12288 per
death averted as compared to
Warfarin
Cost per death averted for
Enoxaparin vs Warfarin varies
between $3581 and $21479
DRAFT FOR CONSULTATION
Bibliographic reference
369
Mol and Egberts, 1994
Netherlands
Study
Type
Patients
characteristics
Economic
analysis:
CEA
Type of surgery:
Hip Fracture
Surgey
Study
design:
Model
Time
horizon:
NR
Discount
rates:
NR
Interventions
Intervention1: NR
prophylaxis
Intervention2:
Dextran
2 x 550 ml IV
Mean age: NR
Intervention3:
reported M/F:
Standard Heparin
Not
5000 U SC twice
daily
Intervention4: Oral
anticoagulants
Pre-existing risk- INR 2.5
Intervention5:
factors: NR
LMWH
1 SC injection/day
Intervention6:
Danaparoid sodium
750 aXa=antifactor
Xa
Timing:
Mean duration of
prophylaxis:
8 days
Additional noncomparative
prophylaxis: NR
Outcome measures
DVT Confirmed by
Doppler sonography
Effect size
Int1: 50%
Int2: 28%
Int4: 23%
Int5: 20%
p value: Not reported
Int1: 12.5%
Int2: 7%
Int4: 5.8%
Int5: 5%
p value: Not reported
Comments
Int3: 27% Funding: Organon
Int6: 9% International
Int3: 6.8% Outcomes not reported: PVT,
Int6: 2.3% FPE, PTS, Bleeding, HRQL,
Survival, LOS, LE, QALE
PE
Confirmed by:
Perfusion ventilation +
chest radiography
Int1: 10%
Int2: 5.6%
5.4%
Int4: 4.6%
4.0%
Int6: 1.8%
value: Not reported
Int3:
Int5:
Fatal PE Confirmed by:
NR
Int1: 5.9%
Int2: 3.3%
3.2%
Int4: 2.7%
2.4%
Int6: 1.1%
value: Not reported
Int3:
Int5:
Cost (Dutch florins, health
care costs of prophylaxis
and treatment of VTE)
Int1: 10%
Int2: 5.6%
5.4%
Int4: 4.6%
4.0%
Int6: 1.8%
value: Not reported
Int3:
Int5:
Cost-effectiveness: (Cost
per life saved)
Danaparoid dominates
Sensitivity analysis:
(charges for diagnosis and
treatment of DVT & PE,
duration of prophylaxis, and
clinical detection rate)
Results were robust except when using
the lower confidence limit for the
Danaparoid effect size. In this case
LMWH was the most cost-effective
strategy.
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p
p
p
Limitations:
Did not include the costs or
health consequences
associated with major bleeding
DRAFT FOR CONSULTATION
Bibliographic
reference
Study Type
Patients
characteristics
Interventions
Outcome measures
Effect size
Comments
Nerurkar et al,
380
2002
Economic
analysis:
Cost
effectiveness
analysis
Type of surgery:
Total Knee
Replacement
Int: Enoxaparin
Dose: 300mg
subcutaneous twice
daily
Timing: 514 days post ops
Survival (Number of deaths per
10000 patients)
Int: 122
Control1: 192
Control2: 316
Funding: NR
USA
Study
design:
Decision
analytic
model
Time
horizon: 514 days post
op
Discount
rates:
Costs=Not
Applicable
Effects=Not
Applicable
Intervention:
Enoxaparin
N: NR
Mean age: >40 yrs
M/F:NR
Control1: Warfarin
N: NR
Mean age: >40 yrs
M/F:NR
Control2: No
prophylaxis
N: NR
Mean age: >40 yrs
M/F:NR
Pre-existing riskfactors:
NR
Control1: Warfarin
Dose: 10mg day
Timing: 5-14 days
post op
Control2: No
prophylaxis Dose:
Timing:
Additional noncomparative
prophylaxis: NR
Deaths averted (per 1000 patients)
Int: 194
Control1: 124
Control2: 0
Mean cost (Costs in 2000 US$;
Costs included: Resources
consumed during hospitalisation,
Number of physician visits,
Resources related to prophylactic
VTE drug administration during
inpatient stay, Laboratory tests,
Complete blood count, Longer
hospital stay & Treatment and
Diagnostic costs for DVT and PE).
Costs expressed as EXPECTED
MEDICAL CHARGES/PATIENT
Cost-effectiveness: (Cost per
death averted)
Int: $26455
Control1:
$27360
Control2: $28766
Sensitivity analysis: Deterministic
sensitivity analysis
Results are robust upon varying
several parameters
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Enoxaparin dominates both
Warfarin & no prophylaxis
Outcomes not
included: DVT,
PE, Bleeding,
HRQL, LOS, LE
DRAFT FOR CONSULTATION
Bibliographic
reference
O'Brien and
390
Goeree, 1994
Canada
Study Type
Patients
characteristics
Economic
analysis:
Cost
Effectiveness
Analysis
Type of surgery:
Total Hip
Replacement
Study
design:
Decision
analysis
Time
horizon: 12
days
Discount
rates:
Costs=NR
Effects = year
of life
discounted at
5%
Intervention:
Enoxaparin
N: NR
Mean age: 68
M/F:NR
Control:
Warfarin
N: NR
Mean age: 68
M/F:NR
Pre-existing
risk-factors:
Interventions
Outcome measures
Effect size
Int: Enoxaparin Dose:
30mg twice daily
Timing: Postop for 11
days (day 3 to day 13)
DVT Confirmed by:
Ultrasonography:
a) Proximal
DVTs
b) Distal DVTs
c) All DVTs
Int: Warfarin Dose:
Preoperative dose of
loading 10mg
Timing: Postop for 12
days (day 2 to day 13)
PE
Confirmed by: Clinically
detected
Post thrombotic leg
Int:
Control:
(Sig/Not sig)
Additional noncomparative
prophylaxis:
Mean cost (1992 Canadian $,
including Prophylaxis, Confirming
clinical diagnosis of DVT,
confirming clinical diagnosis of PE
in pts with or without previous
DVT, Hospitalisation, Intreavenous
heparin treatment)
Life-years Additional life year
used as outcome measure, based
on the assumption that pts
undergoing THR should live other
15 yrs = 10.30 life yrs (5%
discount rate)
Cost-effectiveness: (Cost per life
year gained)
Sensitivity analysis:
Int: Can$355
Can$234
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Comments
a) Int: 4.8
Control: 3.7
p value: (ns)
b) Int: 8.8
Control: 17.0
p value: <.05
c) Int:
13.6
Control: 20.6
p
value: <.05
Int: 2.5%
Control: 2.5%
p
value:
p value:
Control:
p value:
NR
Reported in differential terms.
Enoxaparin saves 4 lives as
compared to Warfarin, therefore
differential in effectiveness is 4 x
10.38 = 41.52 life yrs gained on
10000 pts (discount rate 5%)
Enoxaparin costs Can$29 140 per
life year saved
If overall rate of DVT with
Enoxaparin is set on the lower limit
of 95%CI (10.9), then Cost per life
year gained is Can$6,000.
When upper limit is considered,
(16.3%), Enoxaparin is dominated
Funding: RhônePoulenc Rorer
Outcomes not
included: FPE, PTS,
Bleeding, HRQL,
Survival, LOS
DRAFT FOR CONSULTATION
Bibliographic
reference
Study Type
Patients
characteristics
Interventions
Outcome measures
Effect size
Comments
Oster et al,
399
1987
Economic
analysis: Costeffectiveness
analysis
Type of surgery:
abdominothoracic,
gynaecologic and
prostatic (Duration
of surgery=NR)
1: IPC Details: 50%
thigh, 50% calf Timing:
16 hours
DVT Confirmed by: bilateral
venography
1: 2.11% 2: 1.33% 3: 0.54% 4:
1.15% 5: 0.75% 6: 1.19% 7:
3.24%
Funding: Kendall
Company
USA
Study design:
Decision analysis
Time horizon: NR:
<12 months
Discount rates:
NA
Mean age: NR
M/F:NR
Pre-existing riskfactors:
NR
2: GECS Details: NR
Timing: 7 days
3: IPC+GECS Details:
NR Timing: 16 hours+7
days
PE
Confirmed by: chest x-ray
and ventilation-perfusion lung
scanning
1: 0.27% 2: 0.17% 3: 0.07% 4:
0.15% 5: 0.10% 6: 0.15% 7:
0.42%
Deaths
1: 0.32% 2: 0.20% 3: 0.08% 4:
0.17% 5: 0.11% 6: 0.18% 7:
0.48%
Mean cost (US$; medical costs of
prophylaxis and
diagnosing/treating DVT & PE)
1: $149 2: $75 3: $126 4: $140
5: $149 6: $164 7: $109
Cost-effectiveness:
1, 4, 5, 6, and 7 were dominated
4: LDUH Dose: 5000U
2x daily Timing: 7 days
5: LDUH+GECS Dose:
5000U 2x daily Timing:
7 days
6:
LDUH+dihydroergotamin
e Dose: 5000U+0.6mg
Timing: 7 days
3 vs 2: $42,000 per life saved
Sensitivity analysis:
7: NIL
Additional noncomparative
prophylaxis: NR
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Stockings are the lowest cost
strategy under most scenarios
Outcomes not
included: PTS,
Bleeding, HRQL, LE
Other comments:
Since this is a model,
p-values, etc are NA
DRAFT FOR CONSULTATION
Bibliographic
reference
Study Type
Patients
characteristics
Interventions
Outcome measures
Effect size
Comments
Oster et al,
398
1987a
Economic
analysis: Costeffectiveness
analysis
Type of surgery:
routine hip
replacement,
surgery for neck of
femur fractures or
total knee
replacement
(Duration of
surgery=NR)
1: IPC bilaterally
applied prior to
anaesthesia and
continued for 16h
DVT Confirmed by: bilateral
venography
1: 1.83% 2: 3.92% 3: 3.80% 4:
5.26% 5: 5.14% 6: 2.01% 7:
8.60%
Funding: Kendall
Company
PE
Confirmed by: chest x-ray
and ventilation-perfusion lung
scanning
Deaths
1: 0.28% 2: 0.60% 3: 0.58% 4:
0.81% 5: 0.79% 6: 0.31% 7:
1.32%
1: 0.32% 2: 0.70% 3: 0.67% 4:
0.93% 5: 0.91% 6: 0.36% 7:
1.53%
Outcomes not
included: PTS,
Bleeding, HRQL, LE
Mean cost (US$; medical costs of
prophylaxis and
diagnosing/treating DVT & PE)
1: $184 2: $210 3: $243 4: $330
5: $346 6: $231 7: $365
Cost-effectiveness:
1 (IPC) dominates all other
strategies
Sensitivity analysis:
Stockings are the lowest cost
strategy under most scenarios
USA
Study design:
Decision analysis
Time horizon: NR:
<12 months
Discount rates:
NA
Mean age: NR
M/F:NR
Pre-existing riskfactors:
NR
2: GECS Bilateral worn
continuously until
ambulation or discharge
3: Warfarin
Dose:loading dose of
15mg adjusted to keep
prothrombin time at 10%30% of normal Timing:
5 days
4: LDUH Dose:5000U
2x daily Timing: 5 days
5: LDUH+GECS
Dose:5000U 2x daily
Timing: 5 days
6:
LDUH+dihydroergotamin
e Dose:5000U+0.5mg
Timing: 5 days
7: NIL
Additional noncomparative
prophylaxis:
NR
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Other comments:
Since this is a model,
p-values, etc are NA
DRAFT FOR CONSULTATION
Bibliographic
reference
Study Type
Patients
characteristics
Interventions
Outcome measures
Effect size
Comments
Ramaswami
and
Nicolaides,
420
1996
Economic
analysis: Costeffectiveness
analysis
Type of surgery:
General surgery
(Duration of
surgery=NR)
1: IPC Details:NR
Timing: NR
DVT
1: 7% (5%, 9%) 2: 14% (12%,
16%) 3: 8% (7%, 9%) 4: 6% (5%,
9%) 5: 22%
Funding: NR
UK
Study design:
Simple model
based on literature
review
Mean age: NR
M/F:NR
Time horizon: NR
Discount rates:
Costs=NR
Effects (DVTs
averted)=NA
Pre-existing riskfactors:
NR
2: GCS Details:NR
Timing: NR
3: LDUH Dose:NR
Timing: NR
Cost (UK£, prophylaxis and DVT
treatment; NOT PE treatment)
Cost-effectiveness:
4: LMWH Dose:NR
Timing: NR
5: NIL
Sensitivity analysis:
Additional noncomparative
prophylaxis:
NR
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1: £22 (£9, £35) 2: £21 (£6, £35)
3: £32 (£19, £45) 4: £32 (£19,
£45) 5: £23
3 and 5 are dominated.
Outcomes not
included: PE, PTS,
Bleeding, HRQL,
Survival, LE
2 vs 1: £200 per DVT averted
4 vs 2: £1000 per DVT averted
Other limitations:
Poorly reported. Not
possible to tell
sources of data or
method of pooling
No sensitivity analysis but the very
broad confidence intrervals around
the estimates of cost suggest that
the results are very sensitive
Other comments:
Since this is a model,
p-values, etc are NA
DRAFT FOR CONSULTATION
Bibliographic
reference
Reeves et al,
423
2004
UK
Study
Type
Patients
Economic
analysis:
Cost
consequen
ce
Patient group:
The model
considered 5
separate
indications:
Study
design:
Decision
analysis
A: Prophylaxis of
VTE in major
orthopaedic
surgery patients
B: Prophylaxis of
VTE in major
general surgery
patients
C: Prophylaxis of
VTE in bedridden
medical patients
D: Treatment of
VTE and/or PE
E: Anticoagulation
for patients with
unstable angina or
Myocardial
infarction
Time
horizon:
NR
Discount
rates:NR
Interventions
The model considered
3 scenarios:
Outcome measures
A: 1. 0.25 2. 0.25 3. 0.125
B: 1. 0.149 2. 0.149 3.0.120
C: 1. 0.149 2.0.066 3.0.055
D: 1. 0.051 2.0.043 3.0.043
DVT incidence
1. Unfractionated
heparin (except for C, PE incidence
where 1=no treatment)
2. Multiple heparins (A,
B, and
C=unfractionated
heparins,
D=tinzaparin,
E=dalteparin)
3. Single LWMH,
enoxaparin.
Effect size
D: 1. 0.0182 2. 0.0193 (outpt) 0.0177 (inpt)
3. 0.0193 (outpt) 0.0177 (inpt)
Revascularisation rate
E: 1. 0.32 2. 0.32 3. 0.27
Major bleeding rate (requiring
transfusion of at least 2 units of
blood)
A: 1. 0.16 2. 0.16 3.0.016
B: 1. 0.028 2. 0.028 3.0.040
C: 1. 0.011 2.0.035 3.0.017
D: 1. 0.026 2.0.015 3.0.015
E: 1. 0.070 2.0.065 3.0.065
Mean Cost (£, 2001/2002, All
NHS costs included)
A: 1. £229 2. £229 3. £142
B: 1. £138 2. £138 3. £127
C 1. £579 2. £124 3. £99
D 1. £2082 2. £1432 3. £1328
E 1. £1406 2. £1423 3. £1237
Sensitivity analysis:
Model is sensitive to:
(1) Average duration patients are given
heparin, particularly for patient group E.
(2) The effectiveness of (3) in reducing DVT
Total: 1. £918 2. £786 3. £677
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Comments
Funding: Aventis
Outcomes not included:
FPE, PTS, HRQL, Survival,
LOS, LE.
Other limitations:
Since this is a model, pvalues, etc are NA
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Salzman and
442
Davies, 1980
Economic
analysis:
Cost
consequen
ce
Patient group:
Study
design:
Decision
analysis
A: General
surgical patients
USA
Time
horizon:
NR
Discount
rates: NR
Patients
Two types of
patient groups
were considered:
B: Total hip
replacement
Interventions
Outcome measures
Effect size
Clinical DVT incidence
A: 1. 3.5 2. 1.8 3. 6.0 4. 2.0
B: 1. 12.0 2. 7.0 3. 4.4 4. 7.8 5. 3.2
Clinical PE incidence
A: 1. 1.8 2. 0.6 3. 1.2 4. 0.9
B: 1. 11.0 2. 5.3 3. 1.1 4. 2.0 5. 6.1
2. Heparin (7 days)
Survival (death rate)
A: 1. 1.0 2. 0.3 3. 0.6 4. 0.3
B: 1. 1.8 2. 1.4 3. 0.7 4. 0.0 5. 0.8
3. Dextran (7 days)
Mean Cost (US $, year not
specified, costs include cost of
drug and cost of complications)
Group A:
1. $82 (£40) 2. $88 (£42) 3. $183 (£88) 4.
$86 (£41)
Converted to £ using PPPs
Group B:
1. $364 (£175) 2. $245 (£118) 3. $152 (£73)
4. $147 (£71) 5. $227 (£109)
Cost-effectiveness:
For Group A:
2 vs. 1, $870 (£419) per death averted in
1000 patients
3 vs. 1, $25,176 (£12,134) per death averted
in 1000 patients
4 vs. 1, $620 (£299) per death averted in
1000 patients
Interventions for the
prophlaxis of DVT
considered:
For Group A:
1. No prophylaxis
4. External pneumatic
compression
For Group B:
1. No prophylaxis
2. Heparin (7 days)
3 Warfarin (7 days)
4 Aspirin (7 days)
5 Dextran (7 days)
For Group B:
All prophylaxis options had lower costs and
better survival compared to no prophylaxis
NR
Sensitivity analysis:
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Comments
Funding: NR
Outcomes not included:
DVT FPE, PTS, Bleeding,
HRQL, Survival, LOS, LE.
Other limitations:
Study is 26 years old.
Other comments:
Since this is a model, pvalues, etc are NA
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Patients
characteristics
Sarasin and
Bounameaux,
452
1996
Economic
analysis:
Costeffectivene
ss analysis
Type of surgery: 1: LMWH Dose: NR
Duration: 4 weeks
General surgery
(GI, gynaecologic, post-discharge
urologic, vascular)
2. No post-discharge
prophylaxis
Mean age: NR
M/F: NR
Switzerland
Study
design:
Decision
analysis
Time
horizon:
NR
Discount
rates:
NA
Interventions
Outcome measures
Effect size
Comments
Clinical VTE
1 vs 2: -0.2%
Funding: NR
Mean cost (US$; prophylaxis
diagnosis and treatment costs for
VTE and bleeding)
1 vs 2: $289
Outcomes not included:
FPE, PTS, HRQL, Survival,
LE
Cost-effectiveness: (cost per
VTE averted)
1 vs 2: $55,000 per VTE averted
Pre-existing riskSensitivity analysis: (one-way
Additional nonfactors:
sensitivity analyses on costs and
comparative
NR
baseline risk)
prophylaxis:
All patients received 714 days of
perioperative
antithrombotic
prophylaxis
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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Results were robust to sensitivity analysis –
extended prophylaxis is unlikely to be costeffective
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Patients
characteristics
Interventions
Outcome measures
Effect size
Comments
Sarasin and
Bounameaux,
453
2002
Economic
analysis:
Cost
consequen
ces
analysis
Type of surgery:
Total hip
replacement
1: Oral anticoagulant
Dose: NR
Duration: 4 weeks
post-discharge
DVT
1. 6.5% 2. 11.7% 3. 5.6% 4. 8.8%
Funding: NR
PE
1. 1.3% 2. 2.3% 3. 1.1% 4. 1.8%
Bleeding related complications
(Major bleed)
1. 0.6% 2. 0% 3. 0.5% 4. 0.5%
Outcomes not included:
FPE, PTS, HRQL, Survival,
LE
Study
design:
Decision
analysis.
Similar to
author’s
other
451
study
Pre-existing risk3: LMWH Dose: NR
factors:
Duration: 4 weeks
NR
post-discharge
Mean cost (1999 euro;
prophylaxis diagnosis and
treatment costs for VTE and
bleeding)
1. 605 2. 695 3. 608 4. 568
Cost-effectiveness: (PEs)
2. was excluded due to dominance
1. was excluded due to extended dominance
3. vs 4. cost 6319 per PE averted
Sensitivity analysis:
Extended prophylaxis remained cost saving
except under extreme scenarios.
Switzerland
Time
horizon:
3 months
Discount
rates:
NA
Mean age: NR
M/F:NR
2. No post-discharge
prophylaxis
4: Aspirin
Dose: NR Duration:
4 weeks postdischarge
Additional noncomparative
prophylaxis:
All patients received 710 days of
perioperative
antithrombotic
prophylaxis
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
518 of 648
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Spruill et al,
480
2004
Economic
analysis:
Cost
consequen
ces
USA
Patients
characteristics
Interventions
Outcome measures
Int: Fondaparinux
PVT Confirmed by: NR
Dose: 2.5mg injection PE (non-fatal) Confirmed by:
once daily Timing:
NR
Postop for 5 days
Bleeding related complications
Intervention:
Control: Enoxaparin
N: 517
Dose: 30mg injection
Mean age: NR
Study
twice daily
M/F:NR
design:
34
Timing: Postop for 4
RCT .
days
Methods
Control:
are the
Mean cost (2002 US$; Direct
Additional nonsame as for N: 517
medical costs for prophylaxis,
comparative
three other Mean age: NR
major bleeding, minor bleeding,
prophylaxis:
M/F:NR
studies
PVT, PE)
481,531,532
NR
Cost-effectiveness (Int
Pre-existing riskcompared with Control):
factors:
Time
Sensitivity
analysis:
NR
horizon:
NR
Type of surgery:
Total knee
arthroplasty
Discount
rates:
NA
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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Effect size
Comments
Int: 2.4% Control: 5.4% p value: NR
Funding: NR
Int: 0.2% Control: 0.8% p value: NR
Major
Int: 1.7% Control: 0% p value: NR
Major leading to re-operation
Int: 0.4% Control: 0.2% p value: NR
Minor
Int: 2.7% Control: 3.7% p value: NR
Int: $406 Control: $445 p value: NR
Fondaparinux both reduced costs and
averted VTEs.
At both extremes Fondaparinux was cost
saving. But if the price of enoxaparin was
reduced by 25% then these savings would
disappear.
Outcomes not included:
FPE, PTS, HRQL, Survival,
LE,
Other limitations: Costs
were inflated at 5% per
year instead of using a
price index
Other comments: Costeffectiveness ratios
compared with no
prophylaxis were reported
but were not based on an
incremental analysis and
are therefore excluded
here.
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Patients
characteristics
Interventions
Spruill et al,
481
2004b
Economic
analysis:
Cost
consequen
ces
Type of surgery:
Elective hip
replacement
Int: Fondaparinux
PVT Confirmed by: NR
Dose: 3mg once daily
Timing: From 6h
Bleeding related complications
postop until NR
USA
Study
design:
509
RCT
Methods
are the
same as for
three other
studies
480,531,532
Time
horizon:
10 days
after
surgery
Intervention:
N: NR
Mean age: NR
M/F:NR
Control:
N: NR
Mean age: NR
M/F:NR
Pre-existing riskfactors:
NR
Control: Enoxaparin
Dose: 30mg twice
daily
Timing:
From 12-24h postop
until NR
Additional noncomparative
prophylaxis:
NR
Outcome measures
Effect size
Comments
Int: 0.9% Control: 2.9% p value: NR
Funding: College of
Pharmacy, University of
Georgia. No external
funding
Major
Int: 4.5% Control: 3.5% p value: NR
Minor
Int: 3.4% Control: 3.1% p value: NR
Cost (2002 US$; Direct medical
costs for prophylaxis, major
bleeding, minor bleeding, PVT)
Int: $422 Control: $439 p value: NR
Cost-effectiveness (Int
compared with Control):
Fondaparinux both reduced costs and
averted VTEs.
Sensitivity analysis:
At both extremes Fondaparinux was cost
saving. But if the price of enoxaparin was
reduced by $3 per day then these savings
would disappear.
Discount
rates:
NA
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Outcomes not included:
Distal DVT, PE, FPE, PTS,
HRQL, Survival, LE,
Other limitations: Costs
were inflated at 5% per
year instead of using a
price index
Other comments: Costeffectiveness ratios
compared with NIL were
reported but were not
based on an incremental
analysis and are therefore
excluded here.
DRAFT FOR CONSULTATION
Bibliographic
reference
Sullivan 2004
USA
488
Study
Type
Patients
Economic
analysis:
Cost
consequen
ce
Type of surgery:
1. Total hip
replacement
Mean age: 65
M/F:NR
2. Total knee
Study
replacement
design:
Mean age: 64
Decision
M/F:NR
analysis
3. Hip fracture
based on
established Mean age: 80
M/F:NR
model
(Sullivan
Pre-existing risk2003)
factors: NR
Time
horizon:
90 days
(also some
data at 1
and 5 years
– not
extracted)
Interventions
Int: Fondaparinux
Dose: 2.5mg daily
Timing: 7 days
Control: Enoxaparin
Dose: 30mg twice
daily
Timing: 7
days
Additional noncomparative
prophylaxis:
NR
Outcome measures
Effect size
Clinical VTE (combined surgical Int: 2.87% Control: 4.38%
population) Confirmed by:NR
Fatal PE (combined surgical
population) Confirmed by:NR
Int: 0.23% Control: 0.41%
Bleeding related complications
(major bleed, combined
surgical population)
Int: 2.72% Control: 1.99%
Mean Cost (US $, 2003, Direct
medical costs for prophylaxis,
treatment of VTE, recurrence,
PTS, Major bleeding, False
positives)year & components
included)
Prophylaxis:
Int: $265 Control: $242
Clinical VTE
Int: $247 Control: $388
Major bleed:
Int: $108 Control: $83
Other (false positives)
Int: $77 Control: $73
Total:
Int: $696 (430) Control: $785 (£485)
Converted to £ using PPPs
NR
Cost-effectiveness
Sensitivity analysis: (costs of
treatment, risk reduction assumed Fondaparinux had better efficacy and lower
costs in all scenarios tested.
for VTEs and bleeds, discount
rate, rate of false positives)
Funding: Sanofi
Synthelabo
Outcomes not included:
DVT not separated from
VTE. Model included PTS
and recurrent VTE, but due
to lack of data rates
assumed to be equal
between groups. No data
on HRQL, survival, LOS or
LE.
Other comments:
See Gordois 2003 for the
UK version of this
comparison using the same
model.
Results are also presented
for a ‘label-based analysis’
based on FDA guidelines
for clinical management.
Since this is a model, pvalues, etc are NA
Discount
rates:
Costs=3%
Effects=NR
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
Comments
521 of 648
DRAFT FOR CONSULTATION
Bibliographic
reference
Sullivan et al,
490
2006
Study
Type
Patients
Economic
analysis:
CEA
Type of surgery
(& Duration of
surgery)
Study
design:,
Decision
analysis
Hip fracture
USA
Intervention:
Interventions
5 years
N:cohort of 1000
Mean age: NS
M/F:NS
Effect size
Comments
Int: Fondaparinux
Dose:Fon: 2.5 mg
per day
Timing: 7 days
DVT Confirmed by: NA, 30 days
Control: Enoxaparin
Dose: 30 mg, 2 a day
Timing: 7 days
Fatal PE Confirmed by: NA, 30
days
Int: 5.6 Control: 11.8 p value: NS
(Sig/Not sig)
Bleeding related complications
(Major Bleeding)
Int:19.3 Control: 19
sig)
Fondaparinux
Time
horizon:
Outcome measures
Additional noncomparative
prophylaxis:
Int: 32.3 Control: 56.4 p value: NA
p value:
Outcomes not included:
PE, Post thrombotic leg
NS, Survival, LOS, Life
years, QALYs
(Sig/Not
Costs, discharge: $ 2003
Int: 469
value:
Control: 572
NA
Discount
Control:
rates:
Costs=not
Enoxaparin
stated
Effects=not
stated
N: cohort of 1000
Mean age: NS
M/F:NS
Funding: SanofiSynthelabo
p
Other limitations: There
are several assumptions,
the findings are based on
the results of a single large
study
Other comments:
The paper reports
outcomes and costs at up
to 30 days, 90 , year 1 and
year 5.
Pre-existing riskfactors:
Reported, but not relevant.
Sensitivity analysis:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
522 of 648
DRAFT FOR CONSULTATION
Bibliographi
c reference
Study Type
Szucs and
Schramm,
494
1999
Economic
analysis: Cost
effectiveness
analysis
Germany
Study design:
Deterministic
Decision
Modelling
Time horizon:
1 year
Discount
rates:
Costs=Not
applicable
Effects=Not
applicable
Patients
characteristic
s
Type of
surgery:
General &
Orthopaedic
surgery
Intervention:
Low Molecular
Weight
Heparins
N: 10000
Mean age: NR
M/F:NR
Control:
Unfractionated
Heparins
Pre-existing
risk-factors:
NR
Interventions
Outcome measures
Effect size
Comments
Int: LMWH
Dose: NR; 1 injection per
day
Timing: 8 day
regimen
DVT Confirmed by:
Duplex Ultrasonography,
Unilateral Venogram
General Surgery
Int: 5.31%
Control: 6.74%
p value: NR
Orthopaedic Surgery
Int: 13.84%
Control: 21.22%
p value: NR
Funding: NR
PE
Confirmed by:
Electrocardiogram, Blood
gas analysis, Chest
radiograph, Ventilationperfusion lung scan,
pulmonary angiography
General Surgery
Int: 0.31%
Control: 0.70%
p value: NR
Orthopaedic Surgery
Int: 1.69% Control: 4.21%
p value: NR
Bleeding related
complications
(Confirmed by laboratory
tests)
General Surgery
Int: 2.63% Control: 2.59%
p value: NR
Orthopaedic Surgery
Int: 0.89% Control: 1.29%
p value: NR
Mortality (Number of
expected deaths per
10000 patients)
General Surgery
Int: 5.48 Control: 9.22
p value: NR
Orthopaedic Surgery
Int: 20.81
Control: 43.22
p value: NR
Incremental cost (Costs
expressed in 1999
Deutsch Mark, DM. Costs
included are: Prophylaxis,
Diagnostic, Hospitalisation,
Indirect costs as loss of
productivity).
Int-Control
A Sick Fund, B Hospital
Cost-effectiveness
General Surgery
A: -DM35 (£12)
B: -DM80 (£28)
Orthopaedic Surgery
A: -DM193 (£67)
B: -DM201 (£70)
Sensitivity analysis:
Many deterministic sensitivity analyses
reported. Most of them confirm the results
Control: UFH
Dose: NR; 3 injections
per day
Timing: 8 day regimen
Additional noncomparative
prophylaxis:
NR
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
523 of 648
LMWH dominates UFH
Outcomes not included:
PVT, FPE, Postthrombotic leg, HRQL,
Survival, LOS
DRAFT FOR CONSULTATION
Bibliographic
reference
Tola et al,
500
1999
USA
Study
Type
Patients
Economic
analysis:
Cost
analysis
Patient group:
Trauma patients
admitted to one
center who where
unable to be
anticoagulated.
Study
design:
Prospective Intervention:
study – not N:25
Mean age: 53
controlled
M/F:19/6
Time
horizon:
Control:
Hospital
No control group
stay 15.4
days
Pre-existing riskfactors: NR
Discount
rates: NR
Interventions
1. Placement of vena
cava filter in the
intensive care unit
2: Placement of vena
cava filter in the
operating room.
3: Placement of vena
cava filter in the
radiology suite.
Outcome measures
Effect size
PE
No PEs found in group 1
Mean Cost (US $, year not
specified, cost includes costs of
supplies and administration – it
does NOT include the cost of a
filter as this is assumed to be the
same for all three scenarios)
1. $1544 (£994) 2. $3388 (£2182) 3. $3789
(£2440) (not including the cost of the filter)
Converted to £ using PPPs
NR
Sensitivity analysis:
Additional noncomparative
prophylaxis: NR
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
524 of 648
Comments
Funding: NR
Outcomes not included:
DVT PTS, Bleeding, HRQL,
Survival, LOS, LE.
Other limitations:
(1) The prospective data
was only on those patients
who had filters placed in
ICU. No outcome data
were therefore available for
the other 2 options.
(2) Follow-up is very short
(3) Costs refer to hospital
charges not true costs.
(4) No sensitivity analysis
DRAFT FOR CONSULTATION
Bibliographic
reference
Ververeli et al,
523
1995
US
Study
Type
Patients
Interventions
Economic
analysis:
Cost
consequen
ce
Type of surgery:
Total Knee
Arthroplasty
(Duration of
surgery=NR)
Study
design:
Cohort
analysis
Intervention:
N: 51
Mean age: 69
M/F:14/37
Drop-outs:0
Int: Continuous
passive motion.
Details: Initial setting
of 0 to 30°. Increased
by 10° /day. Timing:
Started in the recovery
room, 20 hrs/day for 1st
7 days then during
daytime for rest of
stay.
Time
horizon: 2
years
Discount
rates: NA
Control:
N:52
Mean age: 70
M/F:16/36
Drop-outs:0
Control: knees
maintained in
extension by padded
roll beneath calf and
ankle. Timing: NR
Additional nonPre-existing risk- comparative
factors: NR
prophylaxis:
1. Physical therapy
protocol. Mobilization
st
on 1 post-op day.
Active assisted knee
range of motion
exercises started on
nd
2 post-op day.
2. Low dose coumadin
for thromboembolic
prophylaxis.
Outcome measures
Effect size
DVT
NR
PE (asymptomatic) Confirmed by:
ventilation-perfusion scan
Int: 1 (2%) Control: 2 (4%) P Value: NR
Other measure of effect: Range
of motion outcomes:
1. At discharge
Mean active extension
Flexion
Flexion contracture
2. At 2 years
Mean active extension
Flexion
Flexion contracture
Length of Hospital Stay (days)
Int: -12.5° (±12.5°) Control: -8.8° (±4.2)
p=0.0001
Int: 81.3° (±13°) Control:: 71.2° (±9.5)
p=0.0002
Int: 9.3° (±4.2°) Control: 6.4° (±3.3)
p=0.0001
Int: -2.2° (±3.7°) Control: -2.6° (±4.2) p=0.65
Int: 109.8° (±8°) Control:: 107.8° (±9.4)
p=0.27
Int: 2.2° (±3.7°) Control: 2.3° (±3.8) p=0.95
Int: 12.1 (±3.1) Control: 12.0 (±3.0) p=0.92
Mean Cost (US $, year not
Int: Additional cost of procedure = $720
specified, costs of procedure only) (£446)
Converted to £ using PPPs
Control: Cost of manipulations = $937
(£580)
NR
Sensitivity analysis:
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
525 of 648
Comments
Funding: NR
Outcomes not included:
FPE, PTS, Bleeding,
HRQL, Survival, LE.
Other limitations:
1. Limited clinical VTE
data, no costs relating to
treatment of VTE
2. Costs limited to cost of
intervention and cost of
manipulation required if
patients did not maintain
th
>50° flexion beyond 10
post-op day.
3. No statistical or
sensitivity analysis on cost
data.
DRAFT FOR CONSULTATION
Bibliographic
reference
Wade, 1999
US
528
Study
Type
Patients
Economic
analysis:
Cost
consequen
ce
Type of surgery:
Hip replacement
surgery
Study
design:
Decision
analysis
Time
horizon: 5
days
Interventions
1. Danaparoid 5-day
prophylaxis
Outcome measures
Proximal DVT - incidence
Converted to £ using PPPs
1: 0.4 2: 3.9 3. 2.8
Cost of each regimen not reported
Comments
Funding: NR
Outcomes not included:
PTS, HRQL, Survival, LOS,
LE.
Other limitations:
2 vs. 1 and 3 vs. 1 Cost saving > $15 (£9) for
each thromboembolic event avoided.
3 vs. 2 Cost saving $6.6 (£4) for each
thromboembolic event avoided.
NR
Sensitivity analysis:
(1) No cost data for the
regimens is given
(2) Short time horizon
(3) No sensitivity analysis
Since this is a model, pvalues, etc are NA
Discount
rates: NR
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
1: 6.2 2: 4.7 3. 4.4
1: 0.4 2: 0.33 3. 0.3
PE
Bleeding related complications
2. Enoxaparin 30mg
daily 5-day prophylaxis Mean Cost (US $, 1997, costs
Pre-existing riskinclude product cost and costs of
3. Enoxaparin 40mg
factors: NR
treatment of DVTs)
daily 5-day prophylaxis
Cost-effectiveness:
Additional noncomparative
prophylaxis: NR
Effect size
526 of 648
DRAFT FOR CONSULTATION
Bibliographic
reference
Wade and
Hawkins,
530
2000
USA
Study
Type
Economic
analysis:
Cost
consequen
ce
Study
design:
Decision
analysis
Time
horizon:
30 days
Discount
rates: NR
Patients
Patient Group:
Total hip
arthroplasty
Interventions
1: Enoxaparin, 40mg
daily for 30 days post
discharge
2: Warfarin 5 mg daily
Pre-existing risk- for 30 days post
discharge
factors: NR
3: Enoxaparin, 40mg
daily for4 days post
discharge, plus
warfarin 5 mg daily for
30 days
Outcome measures
Effect size
Proximal DVT - incidence
1: 6.2 2: 2.9 3. 2.9
PE
1: 0 2: 0 3. 0
Bleeding related complications
1: 0 2: 0 3. 0
Mean Cost (US $, 1998, costs
include product cost and costs of
treatment of DVTs)
1: $873 (£553) 2: $164 (£104) 3: $258
(£163)
Converted to £ using PPPs
Cost-effectiveness:
2 vs. 1: cost savings of $21 (£13) for each
proximal DVT avoided
3 vs. 1: cost savings of $19 (£12) for each
proximal DVT avoided
Sensitivity analysis:
For enoxaparin to be cost-effective, the cost
of drug would have to be reduced by a third
and the incidence of DVT reduced to zero.
Additional noncomparative
prophylaxis: NR
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
527 of 648
Comments
Funding: Rhone-Poulenc
Rorer
Outcomes not included:
PTS, HRQL, Survival, LOS,
LE.
Other limitations:
There was very little
efficacy data for warfarin
and none for warfarin plus
enoxaparin.
Since this is a model, pvalues, etc are NA
DRAFT FOR CONSULTATION
Bibliographic
reference
Wade and
Chisholm,
529
2000
Study Type
Economic
analysis: Cost
effectiveness
analysis
USA
Study design:
Meta analysis
of literature
Time horizon:
10 days post
op
Discount
rates:
Costs=Not
Applicable
Effects=Not
Applicable
Patients
Interventions
characteristics
Type of
Int: Dalteparin
surgery:
Dose: 5000U
Hip fracture
Timing: up to 10
days post op
Intervention:
Dalteparin
N: NR
Mean age: NR
M/F:NR
Control1:
Warfarin
N: NR
Mean age: NR
M/F:NR
Control2:
Danaparoid
N: NR
Mean age: NR
M/F:NR
Pre-existing
risk-factors:
Control1: Warfarin
Dose: NR
Timing: up to 10
days post op
Control2:
Danaparoid Dose:
750q 12 h
Timing: up to 10
days post op
Additional noncomparative
prophylaxis:
Outcome measures
Effect size
Comments
Int: 32.3%
Control1: 21%
Control2: 13.2%
Funding: NR
Proximal DVT Confirmed by:
NR
Int: 12.7%
Control1: 6.6%
Control2: 3.6%
Confirmed by: NR
Int: 8.1%
Control1: 0%
Control2: 0.6%
Other limitations: An
incremental analysis was
not performed for
Danaparoid vs warfarin.
Methods are reported
only very briefly
Bleeding related
complications (Not specified)
Mean cost
Int: 0%
Control1: 5%
Control2: 2.7%
NR
Cost-effectiveness: (Cost per
each thromboembolitic event
averted in 1000 patients)
Warfarin dominates compared with Dalteparin
Danaparoid dominates compared with
Dalteparin
Sensitivity analysis:
Deterministic sensitivity analysis
on a few specific parameters
Confirms the above results
DVT Confirmed by: NR
PE
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
528 of 648
Outcomes not included:
FPE, HRQL, Survival,
LOS, LE
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Patients
characteristics
Interventions
Wade et al,
531
2003
Economic
analysis:
Cost
consequen
ces
Type of surgery:
Elective hip
arthroplasty
1: Fondaparinux
PVT Confirmed by: NR
Dose: 2.5mg injection PE (non-fatal) Confirmed by:
once daily Timing:
NR
6h postop for 4-9 days
Bleeding related complications
2: Enoxaparin
Dose: 30mg injection
twice daily Timing:
postop for 4-9 days
USA
Study
design:
Model
combing
the results
of 2 RCTs
310,512
.
Methods
are the
same as for
three other
studies
480,481,532
Time
horizon:
11 days
postop
1:
N: 2268
Mean age: NR
M/F:NR
2:
N: 1129
Mean age: NR
M/F:NR
3:
N: 1133
Mean age: NR
M/F:NR
3: Enoxaparin
Dose: 40mg injection
once daily
Timing:
started 12h preop for
4-9 days
Additional noncomparative
prophylaxis:
Pre-existing risk- NR
factors:
NR
Outcome measures
Effect size
Comments
1: 1.2% 2: 1.2% 3: 2.5% p value: NR
Funding: NR
1: 0.3% 2: 0% 3: 0.2% p value: NR
Major
1: 2.7% 2: 0.7% 3: 2.6% p value: NR
Major leading to re-operation
1: 0.3% 2: 0.2% 3: 0.3% p value: NR
Minor
1: 2.7% 2: 2.1% 3: 3.4% p value: NR
Mean cost (2002 US$; Direct
medical costs for prophylaxis,
major bleeding, minor bleeding,
PVT, PE)
1: $495 2: $344 3: $416 p value: NR
Cost-effectiveness
60mg Enoxaparin was cost saving and had
fewer VTEs comjpared with the other two
interventions
Sensitivity analysis:
At both extremes 60mg enoxaparin was cost
saving. But if the price of fondaparinux was
reduced by 54% then these savings would
disappear.
Discount
rates:
NA
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
529 of 648
Outcomes not included:
FPE, PTS, HRQL, Survival,
LE
Other limitations: Costs
were inflated at 5% per
year instead of using a
price index
Other comments: Costeffectiveness ratios
compared with NIL were
reported but were not
based on an incremental
analysis and are therefore
excluded here.
DRAFT FOR CONSULTATION
Bibliographic
reference
Study
Type
Patients
characteristics
Interventions
Outcome measures
Effect size
Comments
Wade et al,
532
2004
Economic
analysis:
Cost
consequen
ces
Type of surgery:
Hip fracture
Int: Fondaparinux
Dose: 2.5mg injection
once daily Timing:
Postop (unless surgery
was delayed) for 7
days
PVT Confirmed by: NR
Int: 0.9% Control: 4.3% p value: NR
Funding: NR
USA
Study
design:
142
RCT .
Methods
are the
same as for
three other
studies
480,481,531
Time
horizon:
NR
Intervention:
N: 831
Mean age: NR
M/F:NR
Control:
N: 842
Mean age: NR
M/F:NR
Control: Enoxaparin
Dose: 40mg injection
once daily
Timing: Postop
(unless surgery was
delayed) for 7 days
Pre-existing riskAdditional nonfactors:
comparative
NR
prophylaxis:
NR
PE
NR
(non-fatal) Confirmed by:
Bleeding related complications
Int: 0.1% Control: 0.1% p value: NR
Major
Int: 1.8% Control: 1.9% p value: NR
Major leading to re-operation
Int: 0.4% Control: 0.2% p value: NR
Minor
Int: 4.1% Control: 2.1% p value: NR
Mean cost (2002 US$; Direct
medical costs for prophylaxis,
major bleeding, minor bleeding,
PVT, PE)
Int: $440 Control: $421 p value: NR
Cost-effectiveness
Fondaparinux cost an extra $573 per extra
VTE averted
Sensitivity analysis:
At both extremes enoxaparin was cost
saving. But if the price of fondparinux was
reduced to $40.73 per dose then these
savings would disappear.
Discount
rates:
NA
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
530 of 648
Outcomes not included:
FPE, PTS, HRQL, Survival,
LE,
Other limitations: Costs
were inflated at 5% per
year instead of using a
price index
Other comments: Costeffectiveness ratios
compared with NIL were
reported but were not
based on an incremental
analysis and are therefore
excluded here.
DRAFT FOR CONSULTATION
1
APPENDIX E
2
Meta-analyses forest plots
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
List of figures
FIGURE 1. GCS VS NO PROPHYLAXIS - DVT......................................................................................... 535
FIGURE 2. GCS VS NO PROPHYLAXIS - DVT SUBGROUPED BY LENGTH ................................................ 536
FIGURE 3. GCS VS NO PROPHYLAXIS - PULMONARY EMBOLISM ........................................................... 536
FIGURE 4. GCS VS NO PROPHYLAXIS - PROXIMAL DVT........................................................................ 537
FIGURE 5. IPC DEVICES VS NO PROPHYLAXIS - DVT ............................................................................ 537
FIGURE 6. IPC DEVICES VS NO PROPHYLAXIS - DVT SUB-GROUPED BY LENGTH .................................. 538
FIGURE 7. IPC DEVICES VS NO PROPHYLAXIS - PULMONARY EMBOLISM ............................................... 538
FIGURE 8. IPC DEVICES VS NO PROPHYLAXIS - PROXIMAL DVT........................................................... 539
FIGURE 9. FOOT IMPULSE DEVICES VS NO PROPHYLAXIS - DVT ........................................................... 539
FIGURE 10. FOOT IMPULSE DEVICES VS NO PROPHYLAXIS - PULMONARY EMBOLISM ............................ 539
FIGURE 11. FOOT IMPULSE DEVICES VS NO PROPHYLAXIS - PROXIMAL DVT ........................................ 540
FIGURE 12. MECHANICAL VS NO PROPHYLAXIS - DVT......................................................................... 540
FIGURE 13. MECHANICAL VS NO PROPHYLAXIS – PULMONARY EMBOLISM........................................... 541
FIGURE 14. MECHANICAL VS NO PROPHYLAXIS – PROXIMAL DVT....................................................... 541
FIGURE 15. GCS AS AN ADJUVANT - DVT............................................................................................ 542
FIGURE 16. GCS AS AN ADJUVANT - DVT SUB GROUPED BY LENGTH .................................................. 543
FIGURE 17. GCS AS AN ADJUVANT - PULMONARY EMBOLISM .............................................................. 543
FIGURE 18. GCS AS AN ADJUVANT - PROXIMAL DVT .......................................................................... 544
FIGURE 19. IPC DEVICES AS AN ADJUVANT - DVT ............................................................................... 544
FIGURE 20. IPC DEVICES AS AN ADJUVANT - PULMONARY EMBOLISM .................................................. 545
FIGURE 21. IPC DEVICES AS AN ADJUVANT - PROXIMAL DVT.............................................................. 546
FIGURE 22. FOOT IMPULSE DEVICES AS AN ADJUVANT - DVT .............................................................. 546
FIGURE 23. FOOT IMPULSE DEVICES AS AN ADJUVANT - PROXIMAL DVT ............................................. 547
FIGURE 24. MECHANICAL AS AN ADJUVANT - DVT.............................................................................. 548
FIGURE 25. MECHANICAL AS AN ADJUVANT– PULMONARY EMBOLISM ................................................ 549
FIGURE 26. MECHANICAL AS AN ADJUVANT – PROXIMAL DVT............................................................ 549
FIGURE 27. GRADUATED COMPRESSION STOCKINGS: THIGH VS KNEE LENGTH - DVT .......................... 550
FIGURE 28. IPC DEVICES – THIGH VS CALF LENGTH - DVT .................................................................. 550
FIGURE 29. IPC DEVICES VS GCS - DVT.............................................................................................. 551
FIGURE 30. IPC DEVICES VS GCS - PULMONARY EMBOLISM ................................................................ 551
FIGURE 31. IPC DEVICES VS GCS – PROXIMAL DVT............................................................................ 552
FIGURE 32. FOOT IMPULSE DEVICES VS IPC - DVT .............................................................................. 552
FIGURE 33. FOOT IMPULSE DEVICES VS IPC – PULMONARY EMBOLISM ................................................ 552
FIGURE 34. ES VS NO PROPHYLAXIS - DVT .......................................................................................... 553
FIGURE 35. ES VS NO PROPHYLAXIS - PULMONARY EMBOLISM ............................................................ 553
FIGURE 36. IPC + GCS V ES - DVT ..................................................................................................... 553
FIGURE 37. IPC + GCS V ES – PROXIMAL DVT ................................................................................... 554
FIGURE 38. ORAL ANTICOAGULANTS VS NO PROPHYLAXIS - DVT ....................................................... 555
FIGURE 39. ORAL ANTICOAGULANTS VS NO PROPHYLAXIS – PULMONARY EMBOLISM ......................... 556
FIGURE 40. ORAL ANTICOAGULANTS VS NO PROPHYLAXIS – PROXIMAL DVT ..................................... 556
FIGURE 41. ORAL ANTICOAGULANTS VS NO PROPHYLAXIS – MAJOR BLEED ......................................... 556
FIGURE 42. OAC ADJUVANT – DVT..................................................................................................... 557
FIGURE 43. OAC ADJUVANT – PULMONARY EMBOLISM ....................................................................... 557
FIGURE 44. OAC ADJUVANT – PROXIMAL DVT ................................................................................... 557
FIGURE 45. OAC ADJUVANT – MAJOR BLEED ....................................................................................... 558
FIGURE 46. ADJUSTED VS FIXED DOSE OAC – DVT ............................................................................. 558
FIGURE 47. ADJUSTED VS FIXED DOSE OAC – PULMONARY EMBOLISM................................................ 558
FIGURE 48. ADJUSTED VS FIXED DOSE OAC – PROXIMAL DVT............................................................ 559
FIGURE 49. ADJUSTED VS FIXED DOSE OAC – MAJOR BLEED ............................................................... 559
FIGURE 50. OAC TIMING OF INITIATION – DVT ................................................................................... 559
FIGURE 51. OAC TIMING OF INITIATION – PULMONARY EMBOLISM ...................................................... 560
FIGURE 52. OAC TIMING OF INITIATION – PROXIMAL DVT .................................................................. 560
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
531 of 648
DRAFT FOR CONSULTATION
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
FIGURE 53. OAC TIMING OF INITIATION – MAJOR BLEED ...................................................................... 560
FIGURE 54. OAC DURATION – PULMONARY EMBOLISM ........................................................................ 561
FIGURE 55. OAC DURATION – PROXIMAL DVT.................................................................................... 561
FIGURE 56. OAC DURATION – MAJOR BLEED........................................................................................ 561
FIGURE 57. OAC VS UNFRACTIONATED HEPARIN - DVT ...................................................................... 562
FIGURE 58. OAC VS UNFRACTIONATED HEPARIN – PULMONARY EMBOLISM ........................................ 562
FIGURE 59. OAC VS UNFRACTIONATED HEPARIN – PROXIMAL DVT .................................................... 562
FIGURE 60. OAC VS UNFRACTIONATED HEPARIN – MAJOR BLEED ........................................................ 563
FIGURE 61. OAC VS LWMH - DVT ..................................................................................................... 563
FIGURE 62. OAC VS LWMH – PULMONARY EMBOLISM ....................................................................... 564
FIGURE 63. OAC VS LWMH – PROXIMAL DVT................................................................................... 564
FIGURE 64. OAC VS LWMH – MAJOR BLEED ....................................................................................... 565
FIGURE 65. OAC VS ASPIRIN - DVT ..................................................................................................... 565
FIGURE 66. OAC VS ASPIRIN – PULMONARY EMBOLISM ....................................................................... 565
FIGURE 67. OAC VS ASPIRIN – PROXIMAL DVT ................................................................................... 566
FIGURE 68. OAC VS ASPIRIN – MAJOR BLEED ....................................................................................... 566
FIGURE 69. OAC VS DEXTRAN - DVT .................................................................................................. 566
FIGURE 70. OAC VS DEXTRAN – PULMONARY EMBOLISM .................................................................... 567
FIGURE 71. OAC VS DEXTRAN – PROXIMAL DVT ................................................................................ 567
FIGURE 72. OAC VS DEXTRAN – MAJOR BLEED .................................................................................... 567
FIGURE 73. OAC VS DANAPAROID - DVT............................................................................................. 568
FIGURE 74. OAC VS DANAPAROID – PULMONARY EMBOLISM .............................................................. 568
FIGURE 75. OAC VS DANAPAROID – PROXIMAL DVT .......................................................................... 568
FIGURE 76. OAC VS DANAPAROID – MAJOR BLEED .............................................................................. 569
FIGURE 77. DANAPAROID VS NO PROPHYLAXIS - DVT ......................................................................... 569
FIGURE 78. DANAPAROID VS NO PROPHYLAXIS – PULMONARY EMBOLISM ........................................... 569
FIGURE 79. DANAPAROID VS NO PROPHYLAXIS – PROXIMAL DVT ....................................................... 570
FIGURE 80. DANAPAROID VS DEXTRAN - DVT ..................................................................................... 570
FIGURE 81. DANAPAROID VS DEXTRAN – PULMONARY EMBOLISM ....................................................... 570
FIGURE 82. DANAPAROID VS LMWH - DVT........................................................................................ 571
FIGURE 83. DANAPAROID VS LMWH – PULMONARY EMBOLISM.......................................................... 571
FIGURE 84. DANAPAROID VS LMWH – PROXIMAL DVT...................................................................... 571
FIGURE 85. DANAPAROID VS LMWH – MAJOR BLEED ......................................................................... 572
FIGURE 86. DANAPAROID VS UNFRACTIONATED HEPARIN - DVT......................................................... 572
FIGURE 87. DANAPAROID VS UNFRACTIONATED HEPARIN – PULMONARY EMBOLISM ........................... 572
FIGURE 88. DANAPAROID VS UNFRACTIONATED HEPARIN – PROXIMAL DVT....................................... 573
FIGURE 89. DANAPAROID VS ASPIRIN - DVT ........................................................................................ 573
FIGURE 90. DANAPAROID VS ASPIRIN – PULMONARY EMBOLISM .......................................................... 573
FIGURE 91. DANAPAROID VS ASPIRIN – PROXIMAL DVT ...................................................................... 573
FIGURE 92. DEXTRAN VS NO PROPHYLAXIS – DVT .............................................................................. 574
FIGURE 93. DEXTRAN VS NO PROPHYLAXIS – PULMONARY EMBOLISM ................................................. 574
FIGURE 94. DEXTRAN VS NO PROPHYLAXIS – PROXIMAL DVT............................................................. 575
FIGURE 95. DEXTRAN VS NO PROPHYLAXIS – MAJOR BLEED ................................................................. 575
FIGURE 96. DEXTRAN ADJUVANT – DVT ............................................................................................. 575
FIGURE 97. DEXTRAN ADJUVANT – PULMONARY EMBOLISM ................................................................ 576
FIGURE 98. DEXTRAN ADJUVANT –PROXIMAL DVT............................................................................. 576
FIGURE 99. DEXTRAN ADJUVANT – MAJOR BLEED ................................................................................ 576
FIGURE 100. DEXTRAN VS NO PROPHYLAXIS – SUBGROUPED BY DEXTRAN 40 AND DEXTRAN 70 – DVT
.................................................................................................................................................... 577
FIGURE 101. DEXTRAN VS NO PROPHYLAXIS – SUBGROUPED BY MOLECULAR WEIGHT – PROXIMAL DVT
.................................................................................................................................................... 578
FIGURE 102. DEXTRAN VS LMWH – DVT ........................................................................................... 578
FIGURE 103. DEXTRAN VS LMWH – PULMONARY EMBOLISM ............................................................. 579
FIGURE 104. DEXTRAN VS LMWH – PROXIMAL DVT.......................................................................... 579
FIGURE 105. DEXTRAN VS LMWH – MAJOR BLEED ............................................................................. 579
FIGURE 106. DEXTRAN VS UFH – DVT................................................................................................ 580
FIGURE 107. DEXTRAN VS UFH – PULMONARY EMBOLISM .................................................................. 580
FIGURE 108. DEXTRAN VS UFH – PROXIMAL DVT .............................................................................. 580
FIGURE 109. DEXTRAN VS UFH – MAJOR BLEED .................................................................................. 581
FIGURE 110. DEXTRAN VS ASPIRIN – DVT ........................................................................................... 581
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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DRAFT FOR CONSULTATION
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
FIGURE 111.
FIGURE 112.
FIGURE 113.
FIGURE 114.
FIGURE 115.
FIGURE 116.
FIGURE 117.
FIGURE 118.
FIGURE 119.
FIGURE 120.
FIGURE 121.
FIGURE 122.
FIGURE 123.
FIGURE 124.
DEXTRAN VS ASPIRIN – PROXIMAL DVT.......................................................................... 581
UFH VS NO PROPHYLAXIS – DVT .................................................................................... 582
UFH VS NO PROPHYLAXIS – PULMONARY EMBOLISM....................................................... 583
UFH VS NO PROPHYLAXIS – PROXIMAL DVT................................................................... 584
UFH VS NO PROPHYLAXIS – MAJOR BLEED ...................................................................... 585
LMWH VS NO PROPHYLAXIS – DVT ............................................................................... 586
LMWH VS NO PROPHYLAXIS – PULMONARY EMBOLISM .................................................. 586
LMWH VS NO PROPHYLAXIS – PROXIMAL DVT .............................................................. 587
LMWH VS NO PROPHYLAXIS – MAJOR BLEED .................................................................. 587
LMWH PREOPERATIVE VS POSTOPERATIVE INITIATION – DVT ....................................... 588
LMWH PREOPERATIVE VS POSTOPERATIVE INITIATION – PULMONARY EMBOLISM ......... 588
LMWH PREOPERATIVE VS POSTOPERATIVE INITIATION – PROXIMAL DVT...................... 588
LMWH PREOPERATIVE VS POSTOPERATIVE INITIATION – MAJOR BLEED ......................... 589
LMWH VS NO PROPHYLAXIS – SUBGROUPED BY PREOPERATIVE OR POSTOPERATIVE
INITIATION – DVT ....................................................................................................................... 589
FIGURE 125. LMWH VS NO PROPHYLAXIS – SUBGROUPED BY PREOPERATIVE OR POSTOPERATIVE
INITIATION – PULMONARY EMBOLISM .......................................................................................... 590
FIGURE 126. LMWH VS NO PROPHYLAXIS – SUBGROUPED BY PREOPERATIVE OR POSTOPERATIVE
INITIATION – PROXIMAL DVT ...................................................................................................... 591
FIGURE 127. LMWH VS NO PROPHYLAXIS – SUBGROUPED BY PREOPERATIVE OR POSTOPERATIVE
INITIATION – MAJOR BLEED .......................................................................................................... 592
FIGURE 128. LMWH HIGHER VS LOWER DOSE - DVT .......................................................................... 592
FIGURE 129. LMWH HIGHER VS LOWER DOSE – PULMONARY EMBOLISM ............................................ 593
FIGURE 130. LMWH HIGHER VS LOWER DOSE – PROXIMAL DVT ........................................................ 593
FIGURE 131. LMWH HIGHER VS LOWER DOSE – MAJOR BLEED ............................................................ 593
FIGURE 132. LMWH VS NO PROPHYLAXIS – SUBGROUPED BY DOSE - DVT ......................................... 594
FIGURE 133. LMWH VS NO PROPHYLAXIS – SUBGROUPED BY DOSE – PULMONARY EMBOLISM ........... 595
FIGURE 134. LMWH VS NO PROPHYLAXIS – SUBGROUPED BY DOSE – PROXIMAL DVT ....................... 596
FIGURE 135. LMWH VS NO PROPHYLAXIS – SUBGROUPED BY DOSE – MAJOR BLEED ........................... 597
FIGURE 136. LMWH EXTENDED DURATION – DVT ............................................................................. 598
FIGURE 137. LMWH EXTENDED DURATION – PULMONARY EMBOLISM ................................................ 598
FIGURE 138. LMWH EXTENDED DURATION – PROXIMAL DVT............................................................ 599
FIGURE 139. LMWH EXTENDED DURATION – MAJOR BLEED ................................................................ 599
FIGURE 140. LMWH VS UFH - DVT ................................................................................................... 600
FIGURE 141. LMWH VS UFH – PULMONARY EMBOLISM ..................................................................... 601
FIGURE 142. LMWH VS UFH – PROXIMAL DVT ................................................................................. 602
FIGURE 143. LMWH VS UFH – MAJOR BLEED ..................................................................................... 603
FIGURE 144. FONDAPARINUX VS LMWH – DVT ................................................................................. 604
FIGURE 145. FONDAPARINUX VS LMWH – PULMONARY EMBOLISM .................................................... 604
FIGURE 146. FONDAPARINUX VS LMWH – PROXIMAL DVT................................................................ 604
FIGURE 147. FONDAPARINUX VS LMWH – MAJOR BLEED.................................................................... 605
FIGURE 148. FONDAPARINUX EXTENDED DURATION – DVT ................................................................ 605
FIGURE 149. FONDAPARINUX EXTENDED DURATION – PULMONARY EMBOLISM ................................... 605
FIGURE 150. FONDAPARINUX EXTENDED DURATION – PROXIMAL DVT ............................................... 606
FIGURE 151. FONDAPARINUX EXTENDED DURATION – MAJOR BLEED ................................................... 606
FIGURE 152. ANTIPLATELET VS NO PROPHYLAXIS – DVT .................................................................... 607
FIGURE 153. ANTIPLATELET VS NO PROPHYLAXIS – PROXIMAL DVT................................................... 608
FIGURE 154. ANTIPLATELET VS NO PROPHYLAXIS – MAJOR BLEED....................................................... 609
FIGURE 155. ASPIRIN ADJUVANT - DVT............................................................................................... 610
FIGURE 156. ASPIRIN ADJUVANT – PULMONARY EMBOLISM ................................................................. 610
FIGURE 157. ASPIRIN ADJUVANT – PROXIMAL DVT............................................................................. 611
FIGURE 158. ASPIRIN ADJUVANT – MAJOR BLEED ................................................................................. 612
FIGURE 159. HIGHER DOSE ASPIRIN VS LOWER DOSE ASPIRIN - DVT.................................................... 613
FIGURE 160. HIGHER DOSE ASPIRIN VS LOWER DOSE ASPIRIN – MAJOR BLEED ..................................... 613
FIGURE 161. ASPIRIN VS UNFRACTIONATED HEPARIN - DVT................................................................ 613
FIGURE 162. ASPIRIN VS UNFRACTIONATED HEPARIN – PULMONARY EMBOLISM ................................. 614
FIGURE 163. ASPIRIN VS UNFRACTIONATED HEPARIN – PROXIMAL DVT ............................................. 614
FIGURE 164. ASPIRIN VS UNFRACTIONATED HEPARIN – MAJOR BLEED ................................................. 614
FIGURE 165. MECHANICAL COMPRESSION VS PHARMACOLOGICAL – SUBGROUPED BY
PHARMACOLOGICAL - DVT ......................................................................................................... 615
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2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
FIGURE 166. MECHANICAL COMPRESSION VS PHARMACOLOGICAL – SUBGROUPED BY
PHARMACOLOGICAL – PULMONARY EMBOLISM ........................................................................... 616
FIGURE 167. MECHANICAL COMPRESSION VS PHARMACOLOGICAL – SUBGROUPED BY
PHARMACOLOGICAL – PROXIMAL DVT ....................................................................................... 617
FIGURE 168. MECHANICAL COMPRESSION VS PHARMACOLOGICAL – SUBGROUPED BY
PHARMACOLOGICAL – MAJOR BLEED ........................................................................................... 618
FIGURE 169. ELECTRICAL STIMULATION VS PHARMACOLOGICAL – SUBGROUPED BY PHARMACOLOGICAL
- DVT .......................................................................................................................................... 619
FIGURE 170. ELECTRICAL STIMULATION VS PHARMACOLOGICAL – SUBGROUPED BY PHARMACOLOGICAL
– PULMONARY EMBOLISM ............................................................................................................ 619
FIGURE 171. ELECTRICAL STIMULATION VS PHARMACOLOGICAL – SUBGROUPED BY PHARMACOLOGICAL
– PROXIMAL DVT ........................................................................................................................ 620
FIGURE 172. REGIONAL VS GENERAL ANAESTHESIA - DVT.................................................................. 621
FIGURE 173. REGIONAL VS GENERAL ANAESTHESIA – PULMONARY EMBOLISM ................................... 621
FIGURE 174. REGIONAL VS GENERAL ANAESTHESIA – PROXIMAL DVT ............................................... 622
FIGURE 175. REGIONAL VS GENERAL ANAESTHESIA – MAJOR BLEED .................................................. 622
FIGURE 176. REGIONAL VS GENERAL ANAESTHESIA SUBGROUPED BY SPINAL AND EPIDURAL –DVT... 623
FIGURE 177. REGIONAL VS GENERAL ANAESTHESIA SUBGROUPED BY SPINAL AND EPIDURAL –
PULMONARY EMBOLISM .............................................................................................................. 624
FIGURE 178. REGIONAL + GENERAL VS GENERAL ANAESTHESIA - DVT ............................................... 624
FIGURE 179. FOOT ELEVATION VS NO FOOT ELEVATION - DVT ............................................................ 625
FIGURE 180. FOOT ELEVATION VS NO FOOT ELEVATION – PROXIMAL DVT.......................................... 625
FIGURE 181. IV SALINE VS NO IV SALINE - DVT .................................................................................. 625
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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1
Mechanical prophylaxis
2
Graduated compression stockings (GCS) vs no prophylaxis
3
Figure 1. GCS vs no prophylaxis - DVT
Review:
VTE Mechanical
Comparison: 01 Stockings vs no prophylaxis
Outcome:
01 DVT
Study
or sub-category
ALLEN1983
HOLFORD1976
HUI1996
ROSENGARTEN1970
SCURR1977
SHIRAI1985
TSAPOGAS1971
TURNER1984
TURPIE1989
Stockings
n/N
15/97
11/48
38/86
8/25
8/70
5/126
2/51
0/104
1/86
nil
n/N
RR (random)
95% CI
Weight
%
37/103
23/47
30/54
8/25
26/70
17/126
6/44
4/92
7/90
17.26
15.95
21.45
12.11
13.59
9.88
5.03
1.66
3.07
693
651
Total (95% CI)
Total events: 88 (Stockings), 158 (nil)
Test for heterogeneity: Chi² = 16.99, df = 8 (P = 0.03), I² = 52.9%
Test for overall effect: Z = 3.82 (P = 0.0001)
0.01
4
100.00
0.1
Favours stockings
1
10
RR (random)
95% CI
0.43
0.47
0.80
1.00
0.31
0.29
0.29
0.10
0.15
[0.25,
[0.26,
[0.57,
[0.45,
[0.15,
[0.11,
[0.06,
[0.01,
[0.02,
0.73]
0.85]
1.11]
2.24]
0.63]
0.77]
1.35]
1.80]
1.19]
0.47 [0.32, 0.69]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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1
Figure 2. GCS vs no prophylaxis - DVT subgrouped by length
Review:
VTE Mechanical
Comparison: 01 Stockings vs no prophylaxis
Outcome:
04 DVT - subgrouped by length
Study
or sub-category
Stockings
n/N
nil
n/N
RR (random)
95% CI
Weight
%
01 Thigh length
11/48
23/47
HOLFORD1976
8/70
26/70
SCURR1977
5/126
17/126
SHIRAI1985
2/51
6/44
TSAPOGAS1971
1/86
7/90
TURPIE1989
381
377
Subtotal (95% CI)
Total events: 27 (Stockings), 79 (nil)
Test for heterogeneity: Chi² = 1.94, df = 4 (P = 0.75), I² = 0%
Test for overall effect: Z = 5.15 (P < 0.00001)
02 Knee length
8/25
ROSENGARTEN1970
25
Subtotal (95% CI)
Total events: 8 (Stockings), 8 (nil)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.00 (P = 1.00)
03 Thigh & knee length
38/86
HUI1996
86
Subtotal (95% CI)
Total events: 38 (Stockings), 30 (nil)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.33 (P = 0.18)
15.95
13.59
9.88
5.03
3.07
47.52
0.47
0.31
0.29
0.29
0.15
0.36
8/25
25
12.11
12.11
1.00 [0.45, 2.24]
1.00 [0.45, 2.24]
30/54
54
21.45
21.45
0.80 [0.57, 1.11]
0.80 [0.57, 1.11]
17.26
1.66
18.92
0.43 [0.25, 0.73]
0.10 [0.01, 1.80]
0.41 [0.24, 0.69]
100.00
0.47 [0.32, 0.69]
04 Length not specified
15/97
37/103
ALLEN1983
0/104
4/92
TURNER1984
201
195
Subtotal (95% CI)
Total events: 15 (Stockings), 41 (nil)
Test for heterogeneity: Chi² = 0.99, df = 1 (P = 0.32), I² = 0%
Test for overall effect: Z = 3.34 (P = 0.0009)
693
651
Total (95% CI)
Total events: 88 (Stockings), 158 (nil)
Test for heterogeneity: Chi² = 16.99, df = 8 (P = 0.03), I² = 52.9%
Test for overall effect: Z = 3.82 (P = 0.0001)
0.01
2
3
RR (random)
95% CI
0.1
1
Favours stockings
10
[0.26,
[0.15,
[0.11,
[0.06,
[0.02,
[0.24,
0.85]
0.63]
0.77]
1.35]
1.19]
0.53]
100
Favours nil
Figure 3. GCS vs no prophylaxis - pulmonary embolism
Review:
VTE Mechanical
Comparison: 01 Stockings vs no prophylaxis
Outcome: 02 Pulmonary embolism
Study
or sub-category
HOLFORD1976
TURPIE1989
Stockings
n/N
0/50
0/80
130
Total (95% CI)
Total events: 0 (Stockings), 1 (nil)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.70 (P = 0.48)
nil
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
1/48
0/81
100.00
0.32 [0.01, 7.67]
Not estimable
129
100.00
0.32 [0.01, 7.67]
0.01
4
Weight
%
0.1
Favours stockings
1
10
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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1
Figure 4. GCS vs no prophylaxis - proximal DVT
Review:
VTE Mechanical
Comparison: 01 Stockings vs no prophylaxis
Outcome:
03 Proximal DVT
Study
or sub-category
HOLFORD1976
ROSENGARTEN1970
TURPIE1989
Stockings
n/N
nil
n/N
1/48
0/25
1/86
RR (fixed)
95% CI
Weight
%
60.80
39.20
0.33 [0.04, 3.03]
Not estimable
0.52 [0.05, 5.67]
100.00
0.40 [0.08, 2.03]
3/47
0/25
2/90
159
162
Total (95% CI)
Total events: 2 (Stockings), 5 (nil)
Test for heterogeneity: Chi² = 0.08, df = 1 (P = 0.78), I² = 0%
Test for overall effect: Z = 1.10 (P = 0.27)
0.01
2
0.1
1
Favours stockings
10
RR (fixed)
95% CI
100
Favours nil
3
IPC devices vs no prophylaxis
4
Figure 5. IPC devices vs no prophylaxis - DVT
Review:
VTE Mechanical
Comparison: 04 Intermittent pneumatic compression (IPC) vs no prophylaxis
Outcome: 01 DVT
Study
or sub-category
IPC
n/N
BACHMANN1976
BLACKSHEAR1987
BUTSON1981
BYNKE1987
CLARK1974
CLARKEPEARSON1984A
CLARKEPEARSON1984B
COE1978
FISHER1995
GALLUS1983
HILLS1972
HULL1979
HULL1990
SKILLMAN1978
TURPIE1977
TURPIE1979
WEITZ1986
4/26
0/20
4/62
0/31
0/36
5/55
14/97
1/29
4/145
15/43
7/70
2/32
36/124
4/47
8/65
8/102
0/5
Nil
n/N
RR (random)
95% CI
Weight
%
13/28
0/20
4/57
6/31
7/36
17/52
11/97
5/24
9/159
25/47
23/70
19/28
77/135
12/48
13/63
20/97
2/9
6.28
989
1001
Total (95% CI)
Total events: 112 (IPC), 263 (Nil)
Test for heterogeneity: Chi² = 24.64, df = 15 (P = 0.05), I² = 39.1%
Test for overall effect: Z = 5.37 (P < 0.00001)
0.01
5
0.1
Favours IPC
1
10
RR (random)
95% CI
3.98
1.05
1.06
6.86
8.98
1.87
4.99
12.97
8.45
3.85
16.34
5.69
8.07
8.54
1.03
0.33 [0.12, 0.89]
Not estimable
0.92 [0.24, 3.51]
0.08 [0.00, 1.31]
0.07 [0.00, 1.13]
0.28 [0.11, 0.70]
1.27 [0.61, 2.66]
0.17 [0.02, 1.32]
0.49 [0.15, 1.55]
0.66 [0.40, 1.07]
0.30 [0.14, 0.66]
0.09 [0.02, 0.36]
0.51 [0.37, 0.70]
0.34 [0.12, 0.98]
0.60 [0.27, 1.34]
0.38 [0.18, 0.82]
0.33 [0.02, 5.84]
100.00
0.44 [0.33, 0.59]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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Figure 6. IPC devices vs no prophylaxis - DVT sub-grouped by length
Review:
VTE Mechanical
Comparison: 04 Intermittent pneumatic compression (IPC) vs no prophylaxis
Outcome: 04 DVT - subgrouped by length
Study
or sub-category
IPC
n/N
Nil
n/N
RR (random)
95% CI
Weight
%
01 Thigh length
0/31
6/31
BYNKE1987
4/145
9/159
FISHER1995
36/124
77/135
HULL1990
300
325
Subtotal (95% CI)
Total events: 40 (IPC), 92 (Nil)
Test for heterogeneity: Chi² = 1.77, df = 2 (P = 0.41), I² = 0%
Test for overall effect: Z = 4.58 (P < 0.00001)
02 Knee length
4/62
4/57
BUTSON1981
0/36
7/36
CLARK1974
5/55
17/52
CLARKEPEARSON1984A
14/97
11/97
CLARKEPEARSON1984B
1/29
5/24
COE1978
15/43
25/47
GALLUS1983
7/70
23/70
HILLS1972
2/32
19/28
HULL1979
4/47
12/48
SKILLMAN1978
8/65
13/63
TURPIE1977
8/102
20/97
TURPIE1979
0/5
2/9
WEITZ1986
643
628
Subtotal (95% CI)
Total events: 68 (IPC), 158 (Nil)
Test for heterogeneity: Chi² = 22.33, df = 11 (P = 0.02), I² = 50.7%
Test for overall effect: Z = 3.99 (P < 0.0001)
03 Length not stated
4/26
BACHMANN1976
0/20
BLACKSHEAR1987
46
Subtotal (95% CI)
Total events: 4 (IPC), 13 (Nil)
Test for heterogeneity: not applicable
Test for overall effect: Z = 2.20 (P = 0.03)
0.01
2
3
1.05
4.99
16.34
22.38
0.08
0.49
0.51
0.50
[0.00,
[0.15,
[0.37,
[0.37,
1.31]
1.55]
0.70]
0.67]
3.98
1.06
6.86
8.98
1.87
12.97
8.45
3.85
5.69
8.07
8.54
1.03
71.34
0.92
0.07
0.28
1.27
0.17
0.66
0.30
0.09
0.34
0.60
0.38
0.33
0.43
[0.24,
[0.00,
[0.11,
[0.61,
[0.02,
[0.40,
[0.14,
[0.02,
[0.12,
[0.27,
[0.18,
[0.02,
[0.28,
3.51]
1.13]
0.70]
2.66]
1.32]
1.07]
0.66]
0.36]
0.98]
1.34]
0.82]
5.84]
0.65]
6.28
6.28
0.33 [0.12, 0.89]
Not estimable
0.33 [0.12, 0.89]
100.00
0.44 [0.33, 0.59]
13/28
0/20
48
989
1001
Total (95% CI)
Total events: 112 (IPC), 263 (Nil)
Test for heterogeneity: Chi² = 24.64, df = 15 (P = 0.05), I² = 39.1%
Test for overall effect: Z = 5.37 (P < 0.00001)
0.1
1
Favours IPC
10
RR (random)
95% CI
100
Favours nil
Figure 7. IPC devices vs no prophylaxis - pulmonary embolism
Review:
VTE Mechanical
Comparison: 04 Intermittent pneumatic compression (IPC) vs no prophylaxis
Outcome:
02 Pulmonary embolism
Study
or sub-category
BACHMANN1976
CLARKEPEARSON1984A
CLARKEPEARSON1984B
COE1978
FISHER1995
HULL1990
SKILLMAN1978
IPC
n/N
1/26
2/59
4/104
0/31
6/145
1/152
0/47
nil
n/N
RR (fixed)
95% CI
Weight
%
0.01
4
26.63
5.63
5.51
9.32
47.49
5.42
0.22 [0.03, 1.72]
1.93 [0.18, 20.73]
4.04 [0.46, 35.53]
0.26 [0.01, 6.12]
0.73 [0.27, 2.00]
1.04 [0.07, 16.47]
Not estimable
100.00
0.82 [0.42, 1.60]
5/28
1/57
1/105
1/24
9/159
1/158
0/48
564
579
Total (95% CI)
Total events: 14 (IPC), 18 (nil)
Test for heterogeneity: Chi² = 4.74, df = 5 (P = 0.45), I² = 0%
Test for overall effect: Z = 0.59 (P = 0.56)
0.1
Favours IPC
1
10
RR (fixed)
95% CI
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
538 of 648
DRAFT FOR CONSULTATION
1
Figure 8. IPC devices vs no prophylaxis - proximal DVT
Review:
VTE Mechanical
Comparison: 04 Intermittent pneumatic compression (IPC) vs no prophylaxis
Outcome: 03 Proximal DVT
Study
or sub-category
IPC
n/N
CLARKEPEARSON1984A
CLARKEPEARSON1984B
FISHER1995
GALLUS1983
HULL1979
HULL1990
TURPIE1977
TURPIE1979
1/55
5/97
4/145
10/43
0/32
22/124
0/65
3/102
Nil
n/N
RR (fixed)
95% CI
Weight
%
4/52
1/97
9/159
12/47
7/28
42/135
2/63
8/97
4.89
1.19
10.21
13.63
9.49
47.82
3.02
9.75
663
678
Total (95% CI)
Total events: 45 (IPC), 85 (Nil)
Test for heterogeneity: Chi² = 9.82, df = 7 (P = 0.20), I² = 28.7%
Test for overall effect: Z = 3.44 (P = 0.0006)
100.00
0.01
2
0.1
1
Favours IPC
10
RR (fixed)
95% CI
0.24
5.00
0.49
0.91
0.06
0.57
0.19
0.36
[0.03,
[0.60,
[0.15,
[0.44,
[0.00,
[0.36,
[0.01,
[0.10,
2.05]
42.01]
1.55]
1.89]
0.98]
0.90]
3.96]
1.31]
0.56 [0.41, 0.78]
100
Favours nil
3
Foot impulse devices (foot pumps) vs no prophylaxis
4
Figure 9. Foot impulse devices vs no prophylaxis - DVT
Review:
VTE Mechanical
Comparison: 08 Foot impulse devices vs no prophylaxis
Outcome:
01 DVT
Study
or sub-category
SCURR1981
WILSON1992
Foot impulse devices
n/N
nil
n/N
6/33
5/28
RR (fixed)
95% CI
Weight
%
15/33
19/32
61
65
Total (95% CI)
Total events: 11 (Foot impulse devices), 34 (nil)
Test for heterogeneity: Chi² = 0.23, df = 1 (P = 0.63), I² = 0%
Test for overall effect: Z = 3.55 (P = 0.0004)
0.01
5
0.1
1
Favours foot impulse
10
RR (fixed)
95% CI
45.82
54.18
0.40 [0.18, 0.90]
0.30 [0.13, 0.70]
100.00
0.35 [0.19, 0.62]
100
Favours nil
6
Figure 10. Foot impulse devices vs no prophylaxis - pulmonary
7
embolism
Review:
VTE Mechanical
Comparison: 08 Foot impulse devices vs no prophylaxis
Outcome:
02 Pulmonary embolism
Study
or sub-category
WILSON1992
Foot impulse devices
n/N
0/28
0
Total (95% CI)
Total events: 0 (Foot impulse devices), 0 (nil)
Test for heterogeneity: not applicable
Test for overall effect: not applicable
nil
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
0/32
Not estimable
0
Not estimable
0.01
8
Weight
%
0.1
Favours foot impulse
1
10
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
539 of 648
DRAFT FOR CONSULTATION
1
Figure 11. Foot impulse devices vs no prophylaxis - proximal DVT
Review:
VTE Mechanical
Comparison: 08 Foot impulse devices vs no prophylaxis
Outcome: 03 Proximal DVT
Study
or sub-category
Foot impulse devices
n/N
WILSON1992
nil
n/N
0/28
28
Total (95% CI)
Total events: 0 (Foot impulse devices), 6 (nil)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.69 (P = 0.09)
RR (fixed)
95% CI
RR (fixed)
95% CI
6/32
100.00
0.09 [0.01, 1.49]
32
100.00
0.09 [0.01, 1.49]
0.01
2
Weight
%
0.1
1
Favours foot impulse
10
100
Favours nil
3
4
Mechanical compression prophylaxis (GCS, IPC or foot impulse
devices) vs no prophylaxis
5
Figure 12. Mechanical vs no prophylaxis - DVT
Review:
VTE Mechanical
Comparison: 30 Mechanical vs no prophylaxis
Outcome:
01 DVT
Study
or sub-category
ALLEN1983
BACHMANN1976
BLACKSHEAR1987
BUTSON1981
BYNKE1987
CLARK1974
CLARKEPEARSON1984A
CLARKEPEARSON1984B
COE1978
FISHER1995
GALLUS1983
HILLS1972
HOLFORD1976
HUI1996
HULL1979
HULL1990
ROSENGARTEN1970
SCURR1977
SCURR1981
SHIRAI1985
SKILLMAN1978
TSAPOGAS1971
TURNER1984
TURPIE1977
TURPIE1979
TURPIE1989
WEITZ1986
WILSON1992
Mechanical
n/N
15/97
4/26
0/20
4/62
0/31
0/36
5/55
14/97
1/29
4/145
15/43
7/70
11/48
38/86
2/32
36/124
8/25
8/70
6/33
5/126
4/47
2/51
0/104
8/65
8/102
1/86
0/5
5/28
nil
n/N
RR (random)
95% CI
RR (random)
95% CI
37/103
13/28
0/20
4/57
6/31
7/36
17/52
11/97
5/24
9/159
25/47
23/70
23/47
30/54
19/28
77/135
8/25
26/70
15/33
17/126
12/48
6/44
4/92
13/63
20/97
7/90
2/9
19/32
6.69
3.35
2.10
0.55
0.55
3.67
4.85
0.97
2.64
7.15
4.55
6.06
8.87
2.03
9.16
4.35
4.98
4.31
3.44
3.02
1.64
0.52
4.34
4.60
0.98
0.54
4.12
0.43 [0.25, 0.73]
0.33 [0.12, 0.89]
Not estimable
0.92 [0.24, 3.51]
0.08 [0.00, 1.31]
0.07 [0.00, 1.13]
0.28 [0.11, 0.70]
1.27 [0.61, 2.66]
0.17 [0.02, 1.32]
0.49 [0.15, 1.55]
0.66 [0.40, 1.07]
0.30 [0.14, 0.66]
0.47 [0.26, 0.85]
0.80 [0.57, 1.11]
0.09 [0.02, 0.36]
0.51 [0.37, 0.70]
1.00 [0.45, 2.24]
0.31 [0.15, 0.63]
0.40 [0.18, 0.90]
0.29 [0.11, 0.77]
0.34 [0.12, 0.98]
0.29 [0.06, 1.35]
0.10 [0.01, 1.80]
0.60 [0.27, 1.34]
0.38 [0.18, 0.82]
0.15 [0.02, 1.19]
0.33 [0.02, 5.84]
0.30 [0.13, 0.70]
1743
1717
Total (95% CI)
Total events: 211 (Mechanical), 455 (nil)
Test for heterogeneity: Chi² = 44.31, df = 26 (P = 0.01), I² = 41.3%
Test for overall effect: Z = 7.33 (P < 0.00001)
100.00
0.45 [0.36, 0.56]
0.01
6
Weight
%
0.1
Favours mechanical
1
10
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
540 of 648
DRAFT FOR CONSULTATION
1
Figure 13. Mechanical vs no prophylaxis – pulmonary embolism
Review:
VTE Mechanical
Comparison: 30 Mechanical vs no prophylaxis
Outcome:
02 Pulmonary embolism
Study
or sub-category
BACHMANN1976
CLARKEPEARSON1984A
CLARKEPEARSON1984B
COE1978
FISHER1995
HOLFORD1976
HULL1990
SKILLMAN1978
TURPIE1989
WILSON1992
Mechanical
n/N
nil
n/N
1/26
2/59
4/104
0/31
6/145
0/50
1/152
0/47
0/80
0/28
RR (fixed)
95% CI
Weight
%
5/28
1/57
1/105
1/24
9/159
1/48
1/158
0/48
0/81
0/32
24.56
5.19
5.08
8.59
43.79
7.80
5.00
722
740
Total (95% CI)
Total events: 14 (Mechanical), 19 (nil)
Test for heterogeneity: Chi² = 5.05, df = 6 (P = 0.54), I² = 0%
Test for overall effect: Z = 0.75 (P = 0.45)
100.00
0.01
2
3
0.1
1
Favours mechanical
10
RR (fixed)
95% CI
0.22 [0.03, 1.72]
1.93 [0.18, 20.73]
4.04 [0.46, 35.53]
0.26 [0.01, 6.12]
0.73 [0.27, 2.00]
0.32 [0.01, 7.67]
1.04 [0.07, 16.47]
Not estimable
Not estimable
Not estimable
0.78 [0.40, 1.50]
100
Favours nil
Figure 14. Mechanical vs no prophylaxis – proximal DVT
Review:
VTE Mechanical
Comparison: 30 Mechanical vs no prophylaxis
Outcome: 03 Proximal DVT
Study
or sub-category
CLARKEPEARSON1984A
CLARKEPEARSON1984B
FISHER1995
GALLUS1983
HOLFORD1976
HULL1979
HULL1990
ROSENGARTEN1970
TURPIE1977
TURPIE1979
TURPIE1989
WILSON1992
Mechancial
n/N
1/55
5/97
4/145
10/43
1/48
0/32
22/124
0/25
0/65
3/102
1/86
0/28
nil
n/N
RR (fixed)
95% CI
4/52
1/97
9/159
12/47
3/47
7/28
42/135
0/25
2/63
8/97
2/90
6/32
4.32
1.05
9.02
12.05
3.19
8.39
42.26
850
872
Total (95% CI)
Total events: 47 (Mechancial), 96 (nil)
Test for heterogeneity: Chi² = 11.96, df = 10 (P = 0.29), I² = 16.4%
Test for overall effect: Z = 3.99 (P < 0.0001)
100.00
0.01
4
Weight
%
2.67
8.62
2.05
6.39
0.1
Favours mechanical
1
10
RR (fixed)
95% CI
0.24 [0.03, 2.05]
5.00 [0.60, 42.01]
0.49 [0.15, 1.55]
0.91 [0.44, 1.89]
0.33 [0.04, 3.03]
0.06 [0.00, 0.98]
0.57 [0.36, 0.90]
Not estimable
0.19 [0.01, 3.96]
0.36 [0.10, 1.31]
0.52 [0.05, 5.67]
0.09 [0.01, 1.49]
0.52 [0.38, 0.72]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
541 of 648
DRAFT FOR CONSULTATION
1
2
3
Graduated compression stockings (GCS) as an adjuvant
subgrouped by mechanical or pharmacological background
therapy
4
Figure 15. GCS as an adjuvant - DVT
Review:
VTE Mechanical
Comparison: 03 Stockings as an adjuvant - subgrouped by mech or pharm background
Outcome:
01 DVT
Study
or sub-category
Stockings
n/N
Comparison
n/N
RR (fixed)
95% CI
Weight
%
01 Mechanical background prophylaxis
7/54
6/54
MELLBRING1986
1/78
7/78
SCURR1987
132
132
Subtotal (95% CI)
Total events: 8 (Stockings), 13 (Comparison)
Test for heterogeneity: Chi² = 3.41, df = 1 (P = 0.06), I² = 70.7%
Test for overall effect: Z = 1.13 (P = 0.26)
02 Pharmacological background prophylaxis
0/8
5/10
BARNES1978
0/80
8/80
BERGQVIST1984
3/49
13/48
FREDIN1989
8/32
12/32
KALODIKI1996
7/31
15/31
OHLUND1983
23/89
25/85
RASMUSSEN1998
4/98
12/98
TORNGREN1980
1/86
7/90
WILLEJORGENSEN1985
2/79
12/81
WILLEJORGENSEN1991
552
555
Subtotal (95% CI)
Total events: 48 (Stockings), 109 (Comparison)
Test for heterogeneity: Chi² = 16.03, df = 8 (P = 0.04), I² = 50.1%
Test for overall effect: Z = 5.25 (P < 0.00001)
684
687
Total (95% CI)
Total events: 56 (Stockings), 122 (Comparison)
Test for heterogeneity: Chi² = 19.89, df = 10 (P = 0.03), I² = 49.7%
Test for overall effect: Z = 5.31 (P < 0.00001)
4.88
5.70
10.58
1.17 [0.42, 3.25]
0.14 [0.02, 1.13]
0.62 [0.26, 1.43]
4.03
6.92
10.69
9.77
12.21
20.82
9.77
5.57
9.65
89.42
0.11
0.06
0.23
0.67
0.47
0.88
0.33
0.15
0.17
0.44
100.00
0.01
5
0.1
Favours stockings
1
10
RR (fixed)
95% CI
[0.01,
[0.00,
[0.07,
[0.32,
[0.22,
[0.54,
[0.11,
[0.02,
[0.04,
[0.33,
1.75]
1.00]
0.74]
1.41]
0.98]
1.42]
1.00]
1.19]
0.74]
0.60]
0.46 [0.35, 0.61]
100
Favours comparison
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
542 of 648
DRAFT FOR CONSULTATION
1
Figure 16. GCS as an adjuvant - DVT sub grouped by length
Review:
VTE Mechanical
Comparison: 02 Stockings as an adjuvant intervention
Outcome: 04 DVT - subgrouped by length
Study
or sub-category
Stockings
n/N
Comparison
n/N
RR (random)
95% CI
Weight
%
01 Thigh length
0/8
5/10
BARNES1978
0/80
8/80
BERGQVIST1984
3/49
13/48
FREDIN1989
8/32
12/32
KALODIKI1996
7/54
6/54
MELLBRING1986
1/78
7/78
SCURR1987
4/98
12/98
TORNGREN1980
1/86
7/90
WILLEJORGENSEN1985
485
490
Subtotal (95% CI)
Total events: 24 (Stockings), 70 (Comparison)
Test for heterogeneity: Chi² = 12.10, df = 7 (P = 0.10), I² = 42.2%
Test for overall effect: Z = 3.06 (P = 0.002)
2.74
2.61
9.53
14.53
11.20
4.43
10.43
4.42
59.89
0.11
0.06
0.23
0.67
1.17
0.14
0.33
0.15
0.36
14.56
18.17
32.73
0.47 [0.22, 0.98]
0.88 [0.54, 1.42]
0.68 [0.37, 1.26]
7.38
7.38
0.17 [0.04, 0.74]
0.17 [0.04, 0.74]
100.00
0.42 [0.26, 0.68]
02 Knee length
7/31
15/31
OHLUND1983
23/89
25/85
RASMUSSEN1998
120
116
Subtotal (95% CI)
Total events: 30 (Stockings), 40 (Comparison)
Test for heterogeneity: Chi² = 1.95, df = 1 (P = 0.16), I² = 48.7%
Test for overall effect: Z = 1.23 (P = 0.22)
03 Length not stated
2/79
WILLEJORGENSEN1991
79
Subtotal (95% CI)
Total events: 2 (Stockings), 12 (Comparison)
Test for heterogeneity: not applicable
Test for overall effect: Z = 2.36 (P = 0.02)
12/81
81
684
687
Total (95% CI)
Total events: 56 (Stockings), 122 (Comparison)
Test for heterogeneity: Chi² = 19.89, df = 10 (P = 0.03), I² = 49.7%
Test for overall effect: Z = 3.49 (P = 0.0005)
0.01
2
3
0.1
1
Favours stockings
10
RR (random)
95% CI
[0.01,
[0.00,
[0.07,
[0.32,
[0.42,
[0.02,
[0.11,
[0.02,
[0.18,
1.75]
1.00]
0.74]
1.41]
3.25]
1.13]
1.00]
1.19]
0.69]
100
Favours comparison
Figure 17. GCS as an adjuvant - pulmonary embolism
Review:
VTE Mechanical
Comparison: 03 Stockings as an adjuvant - subgrouped by mech or pharm background
Outcome:
02 Pulmonary embolism
Study
or sub-category
Stockings
n/N
Comparison
n/N
01 Mechanical background prophylaxis - no studies
0
Subtotal (95% CI)
Total events: 0 (Stockings), 0 (Comparison)
Test for heterogeneity: not applicable
Test for overall effect: not applicable
02 Pharmacological background prophylaxis
0/8
BARNES1978
0/49
FREDIN1989
2/32
KALODIKI1996
0/94
WILLEJORGENSEN1991
183
Subtotal (95% CI)
Total events: 2 (Stockings), 9 (Comparison)
Test for heterogeneity: Chi² = 0.93, df = 3 (P = 0.82), I² = 0%
Test for overall effect: Z = 1.77 (P = 0.08)
RR (fixed)
95% CI
RR (fixed)
95% CI
0
Not estimable
3/10
2/48
3/32
1/84
174
30.71
24.62
29.24
15.43
100.00
0.17
0.20
0.67
0.30
0.34
183
174
Total (95% CI)
Total events: 2 (Stockings), 9 (Comparison)
Test for heterogeneity: Chi² = 0.93, df = 3 (P = 0.82), I² = 0%
Test for overall effect: Z = 1.77 (P = 0.08)
100.00
0.34 [0.10, 1.12]
0.01
4
Weight
%
0.1
Favours stockings
1
10
[0.01,
[0.01,
[0.12,
[0.01,
[0.10,
2.96]
3.98]
3.73]
7.22]
1.12]
100
Favours comparison
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
543 of 648
DRAFT FOR CONSULTATION
1
Figure 18. GCS as an adjuvant - proximal DVT
Review:
VTE Mechanical
Comparison: 03 Stockings as an adjuvant - subgrouped by mech or pharm background
Outcome:
03 Proximal DVT
Study
or sub-category
Stockings
n/N
Comparison
n/N
01 Mechanical background prophylaxis
0/78
SCURR1987
0
Subtotal (95% CI)
Total events: 0 (Stockings), 0 (Comparison)
Test for heterogeneity: not applicable
Test for overall effect: not applicable
RR (fixed)
95% CI
Weight
%
RR (fixed)
95% CI
0/78
0
Not estimable
Not estimable
02 Pharmacological background prophylaxis
0/8
4/10
BARNES1978
0/80
1/80
BERGQVIST1984
4/32
9/32
KALODIKI1996
120
122
Subtotal (95% CI)
Total events: 4 (Stockings), 14 (Comparison)
Test for heterogeneity: Chi² = 0.64, df = 2 (P = 0.73), I² = 0%
Test for overall effect: Z = 2.19 (P = 0.03)
198
Total (95% CI)
Total events: 4 (Stockings), 14 (Comparison)
Test for heterogeneity: Chi² = 0.64, df = 2 (P = 0.73), I² = 0%
Test for overall effect: Z = 2.19 (P = 0.03)
200
0.01
2
0.1
1
Favours stockings
10
27.84
10.31
61.86
100.00
0.14
0.33
0.44
0.35
[0.01,
[0.01,
[0.15,
[0.13,
2.20]
8.06]
1.30]
0.90]
100.00
0.35 [0.13, 0.90]
100
Favours comparison
3
IPC devices as an adjuvant
4
Figure 19. IPC devices as an adjuvant - DVT
Review:
VTE Mechanical
Comparison: 06 IPC as an adjuvant - subgrouped by mech or pharm background
Outcome:
01 DVT
Study
or sub-category
IPC
n/N
Comparison
n/N
RR (fixed)
95% CI
Weight
%
01 Mechanical background prophylaxis
1/38
5/39
CAPRINI1983
0/33
0/42
ROKITO1996
7/78
7/80
TURPIE1989
0/18
2/5
WAUTRECHT1996
167
166
Subtotal (95% CI)
Total events: 8 (IPC), 14 (Comparison)
Test for heterogeneity: Chi² = 4.52, df = 2 (P = 0.10), I² = 55.8%
Test for overall effect: Z = 1.59 (P = 0.11)
5.14
02 Pharmacological background prophylaxis
2/21
4/24
ESKANDER1997
7/113
9/118
LIEBERMAN1994
6/35
10/35
SIRAGUSA1994
18/97
21/97
SMITH1978
266
274
Subtotal (95% CI)
Total events: 33 (IPC), 44 (Comparison)
Test for heterogeneity: Chi² = 0.58, df = 3 (P = 0.90), I² = 0%
Test for overall effect: Z = 1.28 (P = 0.20)
03 Mechanical + pharmacological background prophylaxis
4/23
1/21
DICKINSON1998
31/164
36/166
GOLDHABER1995
187
187
Subtotal (95% CI)
Total events: 35 (IPC), 37 (Comparison)
Test for heterogeneity: Chi² = 1.72, df = 1 (P = 0.19), I² = 41.9%
Test for overall effect: Z = 0.24 (P = 0.81)
620
627
Total (95% CI)
Total events: 76 (IPC), 95 (Comparison)
Test for heterogeneity: Chi² = 7.58, df = 8 (P = 0.48), I² = 0%
Test for overall effect: Z = 1.62 (P = 0.11)
5
7.20
3.96
16.30
0.21 [0.03, 1.68]
Not estimable
1.03 [0.38, 2.79]
0.06 [0.00, 1.14]
0.53 [0.25, 1.16]
3.89
9.17
10.42
21.87
45.35
0.57
0.81
0.60
0.86
0.76
1.09
37.27
38.36
3.65 [0.44, 30.12]
0.87 [0.57, 1.34]
0.95 [0.63, 1.44]
100.00
0.01
0.1
Favours IPC
1
10
RR (fixed)
95% CI
[0.12,
[0.31,
[0.24,
[0.49,
[0.51,
2.81]
2.11]
1.47]
1.51]
1.15]
0.80 [0.61, 1.05]
100
Favours comparison
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
544 of 648
DRAFT FOR CONSULTATION
1
Figure 20. IPC devices as an adjuvant - pulmonary embolism
Review:
VTE Mechanical
Comparison:06 IPC as an adjuvant - subgrouped by mech or pharm background
Outcome: 02 Pulmonary embolism
Study
or sub-category
IPC
n/N
01 Mechanical background prophylaxis
1/38
CAPRINI1983
0/18
WAUTRECHT1996
56
Subtotal (95% CI)
Total events: 1 (IPC), 2 (Comparison)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.55 (P = 0.58)
Comparison
n/N
RR (fixed)
95% CI
Weight
%
2/39
0/5
44
3.32
3.32
02 Pharmacological background prophylaxis
1/21
0/24
ESKANDER1997
21/1355
48/1196
RAMOS1996
0/35
0/35
SIRAGUSA1994
3/97
5/97
SMITH1978
1508
1352
Subtotal (95% CI)
Total events: 25 (IPC), 53 (Comparison)
Test for heterogeneity: Chi² = 2.05, df = 2 (P = 0.36), I² = 2.4%
Test for overall effect: Z = 3.57 (P = 0.0004)
0.79
85.80
03 Mechanical + pharmacological background prophylaxis
0/23
0/21
DICKINSON1998
1/164
1/166
GOLDHABER1995
187
187
Subtotal (95% CI)
Total events: 1 (IPC), 1 (Comparison)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.01 (P = 0.99)
1751
1583
Total (95% CI)
Total events: 27 (IPC), 56 (Comparison)
Test for heterogeneity: Chi² = 2.43, df = 4 (P = 0.66), I² = 0%
Test for overall effect: Z = 3.57 (P = 0.0004)
2
0.1
Favours IPC
1
10
0.51 [0.05, 5.43]
Not estimable
0.51 [0.05, 5.43]
8.41
95.01
3.41 [0.15, 79.47]
0.39 [0.23, 0.64]
Not estimable
0.60 [0.15, 2.44]
0.43 [0.27, 0.68]
1.67
1.67
Not estimable
1.01 [0.06, 16.05]
1.01 [0.06, 16.05]
100.00
0.01
RR (fixed)
95% CI
0.44 [0.28, 0.69]
100
Favours comparison
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
545 of 648
DRAFT FOR CONSULTATION
1
Figure 21. IPC devices as an adjuvant - proximal DVT
Review:
VTE Mechanical
Comparison: 06 IPC as an adjuvant - subgrouped by mech or pharm background
Outcome:
03 Proximal
Study
or sub-category
IPC
n/N
Comparison
n/N
RR (fixed)
95% CI
Weight
%
01 Mechanical background prophylaxis
0/38
1/39
CAPRINI1983
1/78
1/80
TURPIE1989
0/18
1/5
WAUTRECHT1996
134
124
Subtotal (95% CI)
Total events: 1 (IPC), 3 (Comparison)
Test for heterogeneity: Chi² = 1.17, df = 2 (P = 0.56), I² = 0%
Test for overall effect: Z = 1.25 (P = 0.21)
9.15
6.10
14.09
29.35
0.34
1.03
0.11
0.37
9.07
24.72
33.79
Not estimable
0.35 [0.01, 8.45]
1.25 [0.37, 4.27]
1.01 [0.33, 3.09]
36.86
36.86
0.84 [0.26, 2.71]
0.84 [0.26, 2.71]
100.00
0.76 [0.38, 1.54]
02 Pharmacological background prophylaxis
0/15
0/16
KILLEWICH2002
0/113
1/118
LIEBERMAN1994
5/35
4/35
SIRAGUSA1994
163
169
Subtotal (95% CI)
Total events: 5 (IPC), 5 (Comparison)
Test for heterogeneity: Chi² = 0.54, df = 1 (P = 0.46), I² = 0%
Test for overall effect: Z = 0.01 (P = 0.99)
03 Mechanical + pharmacological background prophylaxis
5/164
GOLDHABER1995
164
Subtotal (95% CI)
Total events: 5 (IPC), 6 (Comparison)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.29 (P = 0.78)
6/166
166
461
459
Total (95% CI)
Total events: 11 (IPC), 14 (Comparison)
Test for heterogeneity: Chi² = 2.78, df = 5 (P = 0.73), I² = 0%
Test for overall effect: Z = 0.76 (P = 0.45)
0.01
2
0.1
1
Favours IPC
10
RR (fixed)
95% CI
[0.01,
[0.07,
[0.00,
[0.08,
8.14]
16.11]
2.26]
1.76]
100
Favours comparison
3
Foot impulse devices (foot pumps) as an adjuvant
4
Figure 22. Foot impulse devices as an adjuvant - DVT
Review:
VTE Mechanical
Comparison:10 Foot impulse devices as an adjuvant - subgrouped by mech or pharm background
Outcome: 01 DVT
Study
or sub-category
Treatment
n/N
01 Mechanical
4/39
FORDYCE1992
39
Subtotal (95% CI)
Total events: 4 (Treatment), 16 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 2.66 (P = 0.008)
02 pharmacological
0/25
STANNARD1996
25
Subtotal (95% CI)
Total events: 0 (Treatment), 5 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.65 (P = 0.10)
Control
n/N
RR (fixed)
95% CI
Weight
%
16/40
40
74.18
74.18
0.26 [0.09, 0.70]
0.26 [0.09, 0.70]
5/25
25
25.82
25.82
0.09 [0.01, 1.56]
0.09 [0.01, 1.56]
100.00
0.21 [0.08, 0.55]
64
65
Total (95% CI)
Total events: 4 (Treatment), 21 (Control)
Test for heterogeneity: Chi² = 0.47, df = 1 (P = 0.49), I² = 0%
Test for overall effect: Z = 3.20 (P = 0.001)
0.01
5
RR (fixed)
95% CI
0.1
Favours foot impulse
1
10
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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DRAFT FOR CONSULTATION
1
Figure 23. Foot impulse devices as an adjuvant - proximal DVT
Review:
VTE Mechanical
Comparison: 10 Foot impulse devices as an adjuvant - subgrouped by mech or pharm background
Outcome:
03 Proximal DVT
Study
or sub-category
Treatment
n/N
Control
n/N
RR (fixed)
95% CI
Weight
%
01 mechanical
2/39
13/40
FORDYCE1992
0/40
9/39
STRANKS1992
79
79
Subtotal (95% CI)
Total events: 2 (Treatment), 22 (Control)
Test for heterogeneity: Chi² = 0.52, df = 1 (P = 0.47), I² = 0%
Test for overall effect: Z = 3.40 (P = 0.0007)
02 pharmacological
0/25
STANNARD1996
0
Subtotal (95% CI)
Total events: 0 (Treatment), 0 (Control)
Test for heterogeneity: not applicable
Test for overall effect: not applicable
57.17
42.83
100.00
0.16 [0.04, 0.65]
0.05 [0.00, 0.85]
0.11 [0.03, 0.40]
0/25
0
Not estimable
Not estimable
104
104
Total (95% CI)
Total events: 2 (Treatment), 22 (Control)
Test for heterogeneity: Chi² = 0.52, df = 1 (P = 0.47), I² = 0%
Test for overall effect: Z = 3.40 (P = 0.0007)
100.00
0.01
2
RR (fixed)
95% CI
0.1
Favours foot impulse
1
10
0.11 [0.03, 0.40]
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
547 of 648
DRAFT FOR CONSULTATION
1
2
Mechanical compression prophylaxis (GCS, IPC or foot impulse
devices) as an adjuvant
3
Figure 24. Mechanical as an adjuvant - DVT
Review:
VTE Mechanical
Comparison: 13 Mechanical as an adjuvant intervention - subgrouped by mech & pharm background
Outcome:
01 DVT
Study
or sub-category
IPC
n/N
Comparison
n/N
RR (fixed)
95% CI
Weight
%
01 Mechanical background prophylaxis
1/38
5/39
CAPRINI1983
4/39
16/40
FORDYCE1992
7/54
6/54
MELLBRING1986
0/33
0/42
ROKITO1996
1/78
7/78
SCURR1987
7/78
7/80
TURPIE1989
0/18
2/5
WAUTRECHT1996
338
338
Subtotal (95% CI)
Total events: 20 (IPC), 43 (Comparison)
Test for heterogeneity: Chi² = 10.56, df = 5 (P = 0.06), I² = 52.7%
Test for overall effect: Z = 3.12 (P = 0.002)
1.95
6.24
2.37
02 Pharmacological background prophylaxis
0/8
5/10
BARNES1978
0/80
8/80
BERGQVIST1984
4/23
1/21
DICKINSON1998
2/21
4/24
ESKANDER1997
3/49
13/48
FREDIN1989
31/164
36/166
GOLDHABER1995
8/32
12/32
KALODIKI1996
7/113
9/118
LIEBERMAN1994
7/54
6/54
MELLBRING1986
7/31
15/31
OHLUND1983
23/89
25/85
RASMUSSEN1998
1/78
7/78
SCURR1987
6/35
10/35
SIRAGUSA1994
18/97
21/97
SMITH1978
0/25
5/25
STANNARD1996
4/98
12/98
TORNGREN1980
1/86
7/90
WILLEJORGENSEN1985
2/79
12/81
WILLEJORGENSEN1991
1162
1173
Subtotal (95% CI)
Total events: 124 (IPC), 208 (Comparison)
Test for heterogeneity: Chi² = 27.96, df = 17 (P = 0.05), I² = 39.2%
Test for overall effect: Z = 4.97 (P < 0.00001)
1500
1511
Total (95% CI)
Total events: 144 (IPC), 251 (Comparison)
Test for heterogeneity: Chi² = 39.52, df = 23 (P = 0.02), I² = 41.8%
Test for overall effect: Z = 5.82 (P < 0.00001)
2.77
2.73
1.50
17.56
0.21 [0.03, 1.68]
0.26 [0.09, 0.70]
1.17 [0.42, 3.25]
Not estimable
0.14 [0.02, 1.13]
1.03 [0.38, 2.79]
0.06 [0.00, 1.14]
0.46 [0.28, 0.75]
1.96
3.36
0.41
1.47
5.19
14.13
4.74
3.48
2.37
5.93
10.10
2.77
3.95
8.30
2.17
4.74
2.70
4.68
82.44
0.11
0.06
3.65
0.57
0.23
0.87
0.67
0.81
1.17
0.47
0.88
0.14
0.60
0.86
0.09
0.33
0.15
0.17
0.60
100.00
0.01
4
0.1
Favours IPC
1
10
RR (fixed)
95% CI
[0.01,
[0.00,
[0.44,
[0.12,
[0.07,
[0.57,
[0.32,
[0.31,
[0.42,
[0.22,
[0.54,
[0.02,
[0.24,
[0.49,
[0.01,
[0.11,
[0.02,
[0.04,
[0.49,
1.75]
1.00]
30.12]
2.81]
0.74]
1.34]
1.41]
2.11]
3.25]
0.98]
1.42]
1.13]
1.47]
1.51]
1.56]
1.00]
1.19]
0.74]
0.73]
0.58 [0.48, 0.69]
100
Favours comparison
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
548 of 648
DRAFT FOR CONSULTATION
1
Figure 25. Mechanical as an adjuvant– pulmonary embolism
Review:
VTE Mechanical
Comparison: 13 Mechanical as an adjuvant intervention - subgrouped by mech & pharm background
Outcome: 02 Pulmonary embolism
Study
or sub-category
IPC
n/N
comparison
n/N
01 Mechanical background prophylaxis
1/38
CAPRINI1983
0/18
WAUTRECHT1996
56
Subtotal (95% CI)
Total events: 1 (IPC), 2 (comparison)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.55 (P = 0.58)
RR (fixed)
95% CI
Weight
%
2/39
0/5
44
3.24
3.24
02 Pharmacological background prophylaxis
1/21
0/24
ESKANDER1997
1/164
1/166
GOLDHABER1995
21/1355
48/1196
RAMOS1996
0/35
0/35
SIRAGUSA1994
3/97
5/97
SMITH1978
0/94
1/84
WILLEJORGENSEN1991
1766
1602
Subtotal (95% CI)
Total events: 26 (IPC), 55 (comparison)
Test for heterogeneity: Chi² = 2.47, df = 4 (P = 0.65), I² = 0%
Test for overall effect: Z = 3.60 (P = 0.0003)
0.77
1.63
83.58
1822
1646
Total (95% CI)
Total events: 27 (IPC), 57 (comparison)
Test for heterogeneity: Chi² = 2.49, df = 5 (P = 0.78), I² = 0%
Test for overall effect: Z = 3.64 (P = 0.0003)
0.01
2
3
0.1
1
Favours IPC
10
RR (fixed)
95% CI
0.51 [0.05, 5.43]
Not estimable
0.51 [0.05, 5.43]
8.20
2.60
96.76
3.41 [0.15, 79.47]
1.01 [0.06, 16.05]
0.39 [0.23, 0.64]
Not estimable
0.60 [0.15, 2.44]
0.30 [0.01, 7.22]
0.44 [0.28, 0.69]
100.00
0.44 [0.28, 0.68]
100
Comparison
Figure 26. Mechanical as an adjuvant – proximal DVT
Review:
VTE Mechanical
Comparison: 13 Mechanical as an adjuvant intervention - subgrouped by mech & pharm background
Outcome:
03 Proximal DVT
Study
or sub-category
Treatment
n/N
Control
n/N
RR (fixed)
95% CI
Weight
%
01 Mechanical background prophylaxis
0/38
1/39
CAPRINI1983
2/39
13/40
FORDYCE1992
0/40
9/39
STRANKS1992
1/78
1/80
TURPIE1989
0/18
1/5
WAUTRECHT1996
213
203
Subtotal (95% CI)
Total events: 3 (Treatment), 25 (Control)
Test for heterogeneity: Chi² = 2.69, df = 4 (P = 0.61), I² = 0%
Test for overall effect: Z = 3.72 (P = 0.0002)
3.83
33.22
24.89
2.56
5.90
70.41
0.34
0.16
0.05
1.03
0.11
0.16
15.44
29.59
0.84 [0.26, 2.71]
Not estimable
0.35 [0.01, 8.45]
1.25 [0.37, 4.27]
Not estimable
0.92 [0.41, 2.07]
100.00
0.38 [0.22, 0.68]
02 Pharmacological background prophylaxis
5/164
6/166
GOLDHABER1995
0/15
0/16
KILLEWICH2002
0/113
1/118
LIEBERMAN1994
5/35
4/35
SIRAGUSA1994
0/25
0/25
STANNARD1996
352
360
Subtotal (95% CI)
Total events: 10 (Treatment), 11 (Control)
Test for heterogeneity: Chi² = 0.62, df = 2 (P = 0.73), I² = 0%
Test for overall effect: Z = 0.20 (P = 0.84)
3.80
10.35
565
563
Total (95% CI)
Total events: 13 (Treatment), 36 (Control)
Test for heterogeneity: Chi² = 9.95, df = 7 (P = 0.19), I² = 29.7%
Test for overall effect: Z = 3.27 (P = 0.001)
0.01
4
0.1
Favours treatment
1
10
RR (fixed)
95% CI
[0.01,
[0.04,
[0.00,
[0.07,
[0.00,
[0.06,
8.14]
0.65]
0.85]
16.11]
2.26]
0.42]
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
549 of 648
DRAFT FOR CONSULTATION
1
Graduated compression stockings – thigh vs knee length
2
Figure 27. Graduated compression stockings: thigh vs knee length -
3
DVT
Review:
VTE Mechanical
Comparison: 03 Stockings - thigh vs knee length
Outcome: 01 DVT
Study
or sub-category
Thigh length
n/N
Calf length
n/N
RR (fixed)
95% CI
Weight
%
01 Thigh v knee length
3/56
1/58
PORTEOUS1989
6/44
8/44
WILLIAMS1988
100
102
Subtotal (95% CI)
Total events: 9 (Thigh length), 9 (Calf length)
Test for heterogeneity: Chi² = 1.33, df = 1 (P = 0.25), I² = 24.9%
Test for overall effect: Z = 0.02 (P = 0.99)
02 Thigh v knee length as an adjuvant to LMWH
8/195
HOWARD2004
195
Subtotal (95% CI)
Total events: 8 (Thigh length), 11 (Calf length)
Test for heterogeneity: not applicable
Test for overall effect: Z = 2.22 (P = 0.03)
4.17
33.94
38.10
3.11 [0.33, 28.99]
0.75 [0.28, 1.98]
1.01 [0.43, 2.39]
61.90
61.90
0.37 [0.15, 0.89]
0.37 [0.15, 0.89]
100.00
0.61 [0.34, 1.11]
11/99
99
295
201
Total (95% CI)
Total events: 17 (Thigh length), 20 (Calf length)
Test for heterogeneity: Chi² = 3.47, df = 2 (P = 0.18), I² = 42.4%
Test for overall effect: Z = 1.61 (P = 0.11)
0.01
4
0.1
1
Favours Thigh
10
RR (fixed)
95% CI
100
Favours Calf
5
IPC devices – thigh vs calf length
6
Figure 28. IPC devices – thigh vs calf length - DVT
Review:
VTE Mechanical
Comparison: 06 Intermittent pneumatic compression (IPC) - thigh vs calf length
Outcome: 01 DVT
Study
or sub-category
SODERDAHL1997
Thigh
n/N
0/47
47
Total (95% CI)
Total events: 0 (Thigh), 1 (Calf)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.73 (P = 0.46)
Calf
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
1/43
100.00
0.31 [0.01, 7.31]
43
100.00
0.31 [0.01, 7.31]
0.01
7
Weight
%
0.1
Favours thigh
1
10
100
Favours calf
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
550 of 648
DRAFT FOR CONSULTATION
1
IPC devices vs graduated compression stockings (GCS)
2
Figure 29. IPC devices vs GCS - DVT
Review:
VTE Mechanical
Comparison:20 Intermittent pneumatic compression (IPC) vs stockings
Outcome: 01 DVT
Study
or sub-category
Treatment
n/N
01 No background therapy
3/24
HANSBERRY1991
24
Subtotal (95% CI)
Total events: 3 (Treatment), 5 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.70 (P = 0.48)
02 LMWH as a background therapy
0/68
SILBERSACK2004
68
Subtotal (95% CI)
Total events: 0 (Treatment), 18 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 2.78 (P = 0.005)
Control
n/N
OR (fixed)
95% CI
Weight
%
5/25
25
18.36
18.36
0.57 [0.12, 2.71]
0.57 [0.12, 2.71]
18/63
63
81.64
81.64
0.02 [0.00, 0.31]
0.02 [0.00, 0.31]
100.00
0.12 [0.04, 0.38]
92
88
Total (95% CI)
Total events: 3 (Treatment), 23 (Control)
Test for heterogeneity: Chi² = 5.60, df = 1 (P = 0.02), I² = 82.1%
Test for overall effect: Z = 3.61 (P = 0.0003)
0.01
3
4
OR (fixed)
95% CI
0.1
1
Favours treatment
10
100
Favours control
Figure 30. IPC devices vs GCS - pulmonary embolism
Review:
VTE Mechanical
Comparison:20 Intermittent pneumatic compression (IPC) vs stockings
Outcome: 02 Pulmonary embolism
Study
or sub-category
IPC
n/N
01 No background therapy
1/25
HANSBERRY1991
25
Subtotal (95% CI)
Total events: 1 (IPC), 1 (Stockings)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.00 (P = 1.00)
25
Total (95% CI)
Total events: 1 (IPC), 1 (Stockings)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.00 (P = 1.00)
Stockings
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
1/25
25
100.00
100.00
1.00 [0.07, 15.12]
1.00 [0.07, 15.12]
25
100.00
1.00 [0.07, 15.12]
0.01
5
Weight
%
0.1
Favours IPC
1
10
100
Favours stockings
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
551 of 648
DRAFT FOR CONSULTATION
1
Figure 31. IPC devices vs GCS – proximal DVT
Review:
VTE Mechanical
Comparison: 20 Intermittent pneumatic compression (IPC) vs stockings
Outcome: 03 Proximal DVT
Study
or sub-category
IPC
n/N
Stockings
n/N
02 LMWH as a background therapy
0/70
SILBERSACK2004
70
Subtotal (95% CI)
Total events: 0 (IPC), 2 (Stockings)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.05 (P = 0.29)
03 Aspirin as background therapy
4/50
RYAN2002
50
Subtotal (95% CI)
Total events: 4 (IPC), 11 (Stockings)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.84 (P = 0.07)
RR (fixed)
95% CI
Weight
%
RR (fixed)
95% CI
2/69
69
18.63
18.63
0.20 [0.01, 4.03]
0.20 [0.01, 4.03]
11/50
50
81.37
81.37
0.36 [0.12, 1.07]
0.36 [0.12, 1.07]
100.00
0.33 [0.12, 0.92]
120
119
Total (95% CI)
Total events: 4 (IPC), 13 (Stockings)
Test for heterogeneity: Chi² = 0.14, df = 1 (P = 0.71), I² = 0%
Test for overall effect: Z = 2.13 (P = 0.03)
0.01
2
3
0.1
1
Favours IPC
10
100
Favours stockings
4
Foot impulse devices vs intermittent pneumatic compression (IPC)
5
Figure 32. Foot impulse devices vs IPC - DVT
Review:
VTE Mechanical
Comparison:21 Foot impulse devices vs intermittent pneumatic compression (IPC)
Outcome: 01 DVT
Study
or sub-category
ANGLEN1998
WOOD1997
Foot impulse devices
n/N
IPC
n/N
3/68
1/75
RR (fixed)
95% CI
Weight
%
0/49
0/59
143
108
Total (95% CI)
Total events: 4 (Foot impulse devices), 0 (IPC)
Test for heterogeneity: Chi² = 0.12, df = 1 (P = 0.73), I² = 0%
Test for overall effect: Z = 1.21 (P = 0.23)
0.01
6
7
0.1
1
Favours foot impulse
10
RR (fixed)
95% CI
50.92
49.08
5.07 [0.27, 96.02]
2.37 [0.10, 57.10]
100.00
3.75 [0.44, 31.84]
100
Favours IPC
Figure 33. Foot impulse devices vs IPC – pulmonary embolism
Review:
VTE Mechanical
Comparison:21 Foot impulse devices vs intermittent pneumatic compression (IPC)
Outcome: 02 Pulmonary embolism
Study
or sub-category
ANGLEN1998
WOOD1997
Foot impulse devices
n/N
1/69
1/75
IPC
n/N
RR (fixed)
95% CI
Weight
%
0/49
0/59
144
108
Total (95% CI)
Total events: 2 (Foot impulse devices), 0 (IPC)
Test for heterogeneity: Chi² = 0.00, df = 1 (P = 0.97), I² = 0%
Test for overall effect: Z = 0.71 (P = 0.48)
0.01
8
0.1
Favours foot impulse
1
10
RR (fixed)
95% CI
51.07
48.93
2.14 [0.09, 51.53]
2.37 [0.10, 57.10]
100.00
2.25 [0.24, 21.35]
100
Favours IPC
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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Electrical calf stimulation (ES) vs no prophylaxis
2
Figure 34. ES vs no prophylaxis - DVT
Review:
VTE Mechanical
Comparison: 11 Electrical stimulation (ES) vs no prophylaxis
Outcome: 01 DVT
Study
or sub-category
BROWSE1970A
LINDSTROM1982
ES
n/N
9/110
5/37
Control
n/N
RR (fixed)
95% CI
Weight
%
23/110
12/40
147
150
Total (95% CI)
Total events: 14 (ES), 35 (Control)
Test for heterogeneity: Chi² = 0.05, df = 1 (P = 0.82), I² = 0%
Test for overall effect: Z = 3.03 (P = 0.002)
0.01
3
4
0.1
1
Favours ES
10
RR (fixed)
95% CI
66.60
33.40
0.39 [0.19, 0.81]
0.45 [0.18, 1.16]
100.00
0.41 [0.23, 0.73]
100
Favours control
Figure 35. ES vs no prophylaxis - Pulmonary embolism
Review:
VTE Mechanical
Comparison: 11 Electrical stimulation (ES) vs no prophylaxis
Outcome: 02 Pulmonary embolism
Study
or sub-category
LINDSTROM1982
ES
n/N
6/37
Control
n/N
OR (fixed)
95% CI
Weight
%
OR (fixed)
95% CI
14/40
100.00
0.36 [0.12, 1.07]
40
100.00
0.36 [0.12, 1.07]
37
Total (95% CI)
Total events: 6 (ES), 14 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.84 (P = 0.07)
0.01
5
0.1
1
Favours ES
10
100
Favours control
6
IPC + GCS v electrical calf stimulation (ES)
7
Figure 36. IPC + GCS v ES - DVT
Review:
VTE Mechanical
Comparison: 22 Intermittent pneumatic compression (IPC) + stockings vs electrical calf stimulation (ES)
Outcome:
01 DVT
Study
or sub-category
NICOLAIDES1983
Treatment
n/N
3/50
50
Total (95% CI)
Total events: 3 (Treatment), 12 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 2.35 (P = 0.02)
Control
n/N
OR (fixed)
95% CI
OR (fixed)
95% CI
12/50
100.00
0.20 [0.05, 0.77]
50
100.00
0.20 [0.05, 0.77]
0.01
8
Weight
%
0.1
Favours treatment
1
10
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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DRAFT FOR CONSULTATION
1
Figure 37. IPC + GCS v ES – proximal DVT
Review:
VTE Mechanical
Comparison: 22 Intermittent pneumatic compression (IPC) + stockings vs electrical calf stimulation (ES)
Outcome:
02 Proximal DVT
Study
or sub-category
NICOLAIDES1983
Treatment
n/N
0/50
50
Total (95% CI)
Total events: 0 (Treatment), 2 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.06 (P = 0.29)
Control
n/N
OR (fixed)
95% CI
OR (fixed)
95% CI
2/50
100.00
0.19 [0.01, 4.10]
50
100.00
0.19 [0.01, 4.10]
0.01
2
3
Weight
%
0.1
Favours treatment
1
10
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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1
Pharmacological prophylaxis
2
Oral anticoagulants vs no prophylaxis
3
Figure 38. Oral anticoagulants vs no prophylaxis - DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 01 OAC vs no prophylaxis
Outcome: 01 DVT
Study
or sub-category
OAC
n/N
BORGSTROM1965
FORDYCE1991
HAMILTON1970
MACCALLUM1990
MORRIS1976
MYHRE1969
PINTO1970
POLLER1987
POWERS1989
TABERNER1978
2/23
25/74
10/38
2/40
23/75
9/44
9/25
4/67
13/65
3/48
Control
n/N
RR (random)
95% CI
Weight
%
5.48
13.63
12.09
4.48
15.15
11.83
10.37
7.52
12.97
6.48
13/25
19/74
18/37
5/46
50/74
22/41
8/25
11/37
29/63
11/48
499
470
Total (95% CI)
Total events: 100 (OAC), 186 (Control)
Test for heterogeneity: Chi² = 25.55, df = 9 (P = 0.002), I² = 64.8%
Test for overall effect: Z = 3.56 (P = 0.0004)
100.00
0.01
4
5
0.1
Favours OAC
1
10
RR (random)
95% CI
0.17
1.32
0.54
0.46
0.45
0.38
1.13
0.20
0.43
0.27
[0.04,
[0.80,
[0.29,
[0.09,
[0.31,
[0.20,
[0.52,
[0.07,
[0.25,
[0.08,
0.66]
2.17]
1.01]
2.24]
0.66]
0.73]
2.44]
0.59]
0.76]
0.92]
0.49 [0.34, 0.73]
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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1
Figure 39. Oral anticoagulants vs no prophylaxis – pulmonary embolism
Review:
VTE Oral anticoagulants and Dextrans
Comparison:01 OAC vs no prophylaxis
Outcome: 02 Pulmonary embolism
Study
or sub-category
BORGSTROM1965
ESKELAND1966
MORRIS1976
MYHRE1969
POWERS1989
OAC
n/N
Control
n/N
0/23
3/100
0/75
1/44
0/65
RR (fixed)
95% CI
Weight
%
8.07
30.26
28.77
24.37
8.53
2/25
9/100
8/74
7/41
2/63
307
303
Total (95% CI)
Total events: 4 (OAC), 28 (Control)
Test for heterogeneity: Chi² = 1.58, df = 4 (P = 0.81), I² = 0%
Test for overall effect: Z = 3.71 (P = 0.0002)
100.00
0.01
2
3
0.1
1
Favours OAC
10
RR (fixed)
95% CI
0.22
0.33
0.06
0.13
0.19
[0.01,
[0.09,
[0.00,
[0.02,
[0.01,
4.29]
1.20]
0.99]
1.04]
3.96]
0.18 [0.08, 0.45]
100
Favours control
Figure 40. Oral anticoagulants vs no prophylaxis – proximal DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 01 OAC vs no prophylaxis
Outcome: 03 Proximal DVT
Study
or sub-category
FORDYCE1991
MACCALLUM1990
MORRIS1976
POWERS1989
OAC
n/N
Control
n/N
6/74
0/40
0/75
6/65
RR (random)
95% CI
Weight
%
5/74
0/46
5/74
19/63
39.47
254
257
Total (95% CI)
Total events: 12 (OAC), 29 (Control)
Test for heterogeneity: Chi² = 4.90, df = 2 (P = 0.09), I² = 59.2%
Test for overall effect: Z = 1.31 (P = 0.19)
0.01
4
5
6
0.1
1
Favours OAC
10
RR (random)
95% CI
13.91
46.62
1.20 [0.38, 3.76]
Not estimable
0.09 [0.01, 1.59]
0.31 [0.13, 0.72]
100.00
0.44 [0.13, 1.50]
100
Favours control
Figure 41. Oral anticoagulants vs no prophylaxis – major bleed
Review:
VTE Oral anticoagulants and Dextrans
Comparison:01 OAC vs no prophylaxis
Outcome: 04 Major bleed
Study
or sub-category
OAC
n/N
BORGSTROM1965
ESKELAND1966
HAMILTON1970
MACCALLUM1990
MORRIS1976
PINTO1970
POLLER1987
POWERS1989
TABERNER1978
0/29
1/100
11/38
4/97
9/80
1/25
12/67
5/65
3/48
Control
n/N
RR (fixed)
95% CI
Weight
%
0/29
2/100
9/38
2/97
2/80
0/25
5/37
5/63
0/48
7.27
32.70
7.27
7.27
1.82
23.41
18.45
1.82
549
517
Total (95% CI)
Total events: 46 (OAC), 25 (Control)
Test for heterogeneity: Chi² = 5.20, df = 7 (P = 0.64), I² = 0%
Test for overall effect: Z = 2.00 (P = 0.05)
100.00
0.01
7
8
9
0.1
Favours OAC
1
10
RR (fixed)
95% CI
Not estimable
0.50 [0.05, 5.43]
1.22 [0.57, 2.61]
2.00 [0.38, 10.67]
4.50 [1.00, 20.18]
3.00 [0.13, 70.30]
1.33 [0.51, 3.47]
0.97 [0.29, 3.19]
7.00 [0.37, 131.96]
1.58 [1.01, 2.47]
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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OAC as an adjuvant
2
Figure 42. OAC adjuvant – DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 02 OAC as an adjuvant intervention
Outcome:
01 DVT
Study
or sub-category
OAC
n/N
HUME1973
KORVALD1973
ROKITO1996
VANGELOVEN1977
3/17
4/39
0/35
13/74
Control
n/N
RR (fixed)
95% CI
Weight
%
4/19
15/43
0/42
15/80
11.64
43.95
165
184
Total (95% CI)
Total events: 20 (OAC), 34 (Control)
Test for heterogeneity: Chi² = 3.64, df = 2 (P = 0.16), I² = 45.1%
Test for overall effect: Z = 1.72 (P = 0.08)
0.01
3
4
0.1
1
Favours OAC
10
RR (fixed)
95% CI
44.41
0.84 [0.22, 3.22]
0.29 [0.11, 0.81]
Not estimable
0.94 [0.48, 1.83]
100.00
0.64 [0.39, 1.06]
100
Favours control
Figure 43. OAC adjuvant – pulmonary embolism
Review:
VTE Oral anticoagulants and Dextrans
Comparison:02 OAC as an adjuvant intervention
Outcome: 02 Pulmonary embolism
Study
or sub-category
KORVALD1973
VANGELOVEN1977
WOOLSON1991
OAC
n/N
Control
n/N
0/39
2/74
0/69
RR (fixed)
95% CI
Weight
%
0.01
5
6
22.92
77.08
0.37 [0.02, 8.75]
0.43 [0.09, 2.16]
Not estimable
100.00
0.42 [0.10, 1.75]
1/43
5/80
0/75
182
198
Total (95% CI)
Total events: 2 (OAC), 6 (Control)
Test for heterogeneity: Chi² = 0.01, df = 1 (P = 0.93), I² = 0%
Test for overall effect: Z = 1.19 (P = 0.23)
0.1
1
Favours OAC
10
RR (fixed)
95% CI
100
Favours control
Figure 44. OAC adjuvant – proximal DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison:02 OAC as an adjuvant intervention
Outcome: 03 Proximal DVT
Study
or sub-category
KORVALD1973
WOOLSON1991
OAC
n/N
1/39
6/69
Control
n/N
RR (fixed)
95% CI
Weight
%
2/43
9/76
108
119
Total (95% CI)
Total events: 7 (OAC), 11 (Control)
Test for heterogeneity: Chi² = 0.05, df = 1 (P = 0.83), I² = 0%
Test for overall effect: Z = 0.77 (P = 0.44)
0.01
7
8
0.1
Favours OAC
1
10
RR (fixed)
95% CI
18.17
81.83
0.55 [0.05, 5.84]
0.73 [0.28, 1.96]
100.00
0.70 [0.28, 1.73]
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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1
Figure 45. OAC adjuvant – major bleed
Review:
VTE Oral anticoagulants and Dextrans
Comparison:02 OAC as an adjuvant intervention
Outcome: 04 Major bleed
Study
or sub-category
HUME1973
ROKITO1996
VANGELOVEN1977
OAC
n/N
Control
n/N
1/17
2/35
1/74
RR (fixed)
95% CI
Weight
%
50.21
24.23
25.56
1/19
0/42
0/80
126
141
Total (95% CI)
Total events: 4 (OAC), 1 (Control)
Test for heterogeneity: Chi² = 0.70, df = 2 (P = 0.70), I² = 0%
Test for overall effect: Z = 1.27 (P = 0.20)
100.00
0.01
2
3
0.1
1
Favours OAC
10
RR (fixed)
95% CI
1.12 [0.08, 16.52]
5.97 [0.30, 120.42]
3.24 [0.13, 78.31]
2.84 [0.57, 14.19]
100
Favours control
4
Adjusted vs fixed (lower) dose oral anticoagulants
5
Figure 46. Adjusted vs fixed dose OAC – DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison:03 OAC adjusted v fixed mini-dose
Outcome: 01 DVT
Study
or sub-category
BERN2002
FELLER1992
POLLER1987
Adjusted
n/N
Fixed mini
n/N
0/43
16/98
1/35
RR (fixed)
95% CI
Weight
%
0/35
30/97
3/32
176
164
Total (95% CI)
Total events: 17 (Adjusted), 33 (Fixed mini)
Test for heterogeneity: Chi² = 0.23, df = 1 (P = 0.64), I² = 0%
Test for overall effect: Z = 2.55 (P = 0.01)
0.01
6
7
0.1
1
Favours adjusted
10
RR (fixed)
95% CI
90.58
9.42
Not estimable
0.53 [0.31, 0.90]
0.30 [0.03, 2.78]
100.00
0.51 [0.30, 0.85]
100
Favours fixed
Figure 47. Adjusted vs fixed dose OAC – pulmonary embolism
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 03 OAC adjusted v fixed mini-dose
Outcome:
02 Pulmonary embolism
Study
or sub-category
BERN2002
FELLER1992
Adjusted
n/N
0/43
1/98
141
Total (95% CI)
Total events: 1 (Adjusted), 0 (Fixed)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.67 (P = 0.50)
Fixed
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
0/35
0/97
100.00
Not estimable
2.97 [0.12, 72.01]
132
100.00
2.97 [0.12, 72.01]
0.01
8
9
Weight
%
0.1
Favours adjusted
1
10
100
Favours fixed
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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Figure 48. Adjusted vs fixed dose OAC – proximal DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison:03 OAC adjusted v fixed mini-dose
Outcome: 03 Proximal DVT
Study
or sub-category
FELLER1992
Adjusted
n/N
Fixed
n/N
RR (fixed)
95% CI
4/98
11/97
98
Total (95% CI)
Total events: 4 (Adjusted), 11 (Fixed)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.81 (P = 0.07)
97
0.01
2
3
4
5
Weight
%
0.1
1
Favours Adjusted
10
RR (fixed)
95% CI
100.00
0.36 [0.12, 1.09]
100.00
0.36 [0.12, 1.09]
100
Favours Fixed
Figure 49. Adjusted vs fixed dose OAC – major bleed
Review:
VTE Oral anticoagulants and Dextrans
Comparison:03 OAC adjusted v fixed mini-dose
Outcome: 04 Major bleed
Study
or sub-category
FELLER1992
POLLER1987
Adjusted
n/N
Fixed
n/N
RR (fixed)
95% CI
0/100
8/35
Weight
%
2/100
4/32
135
132
Total (95% CI)
Total events: 8 (Adjusted), 6 (Fixed)
Test for heterogeneity: Chi² = 1.89, df = 1 (P = 0.17), I² = 47.2%
Test for overall effect: Z = 0.40 (P = 0.69)
0.01
6
7
0.1
1
Favours Adjusted
8
OAC timing of initiation
9
Figure 50. OAC timing of initiation – DVT
10
RR (fixed)
95% CI
37.43
62.57
0.20 [0.01, 4.11]
1.83 [0.61, 5.50]
100.00
1.22 [0.47, 3.18]
100
Favours Fix
Review:
VTE Oral anticoagulants and Dextrans
Comparison:17 OAC timing
Outcome: 01 DVT
Study
or sub-category
FRANCIS1996
Early
n/N
37/95
95
Total (95% CI)
Total events: 37 (Early), 38 (Standard)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.19 (P = 0.85)
Standard
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
38/101
100.00
1.04 [0.73, 1.48]
101
100.00
1.04 [0.73, 1.48]
0.01
10
Weight
%
0.1
Favours early
1
10
100
Favours standard
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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1
Figure 51. OAC timing of initiation – pulmonary embolism
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 17 OAC timing
Outcome:
02 Pulmonary embolism
Study
or sub-category
FRANCIS1996
Early
n/N
Standard
n/N
0/103
RR (fixed)
95% CI
RR (fixed)
95% CI
0/105
0
Total (95% CI)
Total events: 0 (Early), 0 (Standard)
Test for heterogeneity: not applicable
Test for overall effect: not applicable
Not estimable
0
Not estimable
0.01
2
3
Weight
%
0.1
1
Favours early
10
100
Favours standard
Figure 52. OAC timing of initiation – proximal DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 17 OAC timing
Outcome: 03 Proximal DVT
Study
or sub-category
Early
n/N
FRANCIS1996
SWIERSTRA1988
5/95
12/50
Standard
n/N
RR (fixed)
95% CI
Weight
%
7/101
11/51
145
152
Total (95% CI)
Total events: 17 (Early), 18 (Standard)
Test for heterogeneity: Chi² = 0.32, df = 1 (P = 0.57), I² = 0%
Test for overall effect: Z = 0.08 (P = 0.94)
0.01
4
5
6
0.1
1
Favours early
10
RR (fixed)
95% CI
38.39
61.61
0.76 [0.25, 2.31]
1.11 [0.54, 2.28]
100.00
0.98 [0.53, 1.79]
100
Favours standard
Figure 53. OAC timing of initiation – major bleed
Review:
VTE Oral anticoagulants and Dextrans
Comparison:17 OAC timing
Outcome: 04 Major bleed
Study
or sub-category
FRANCIS1996
Early
n/N
5/103
103
Total (95% CI)
Total events: 5 (Early), 2 (Standard)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.13 (P = 0.26)
Standard
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
2/105
100.00
2.55 [0.51, 12.84]
105
100.00
2.55 [0.51, 12.84]
0.01
7
Weight
%
0.1
Favours early
1
10
100
Favours standard
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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1
OAC duration
2
Figure 54. OAC duration – pulmonary embolism
Review:
VTE Oral anticoagulants and Dextrans
Comparison:04 OAC duration
Outcome: 01 Pulmonary embolism
Study
or sub-category
PRANDONI2002
Extended
n/N
Control
n/N
0/184
184
Total (95% CI)
Total events: 0 (Extended), 1 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.70 (P = 0.48)
RR (fixed)
95% CI
Weight
%
RR (fixed)
95% CI
1/176
100.00
0.32 [0.01, 7.78]
176
100.00
0.32 [0.01, 7.78]
0.01
0.1
1
3
4
Favours extended
5
Figure 55. OAC duration – proximal DVT
10
100
Favours control
Review:
VTE Oral anticoagulants and Dextrans
Comparison:04 OAC duration
Outcome: 02 Proximal DVT
Study
or sub-category
PRANDONI2002
Extended
n/N
Control
n/N
1/184
184
Total (95% CI)
Total events: 1 (Extended), 8 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 2.01 (P = 0.04)
RR (fixed)
95% CI
RR (fixed)
95% CI
8/176
100.00
0.12 [0.02, 0.95]
176
100.00
0.12 [0.02, 0.95]
0.01
6
7
8
Weight
%
0.1
1
Favours extended
10
100
Favours control
Figure 56. OAC duration – major bleed
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 04 OAC duration
Outcome:
03 Major bleed
Study
or sub-category
PRANDONI2002
Extended
n/N
1/184
184
Total (95% CI)
Total events: 1 (Extended), 0 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.65 (P = 0.52)
Control
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
0/176
100.00
2.87 [0.12, 69.99]
176
100.00
2.87 [0.12, 69.99]
0.01
9
Weight
%
0.1
Favours extended
1
10
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
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DRAFT FOR CONSULTATION
1
OAC vs unfractionated heparin
2
Figure 57. OAC vs unfractionated heparin - DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 05 OAC vs UFH
Outcome: 01 DVT
Study
or sub-category
OAC
n/N
BARBER1977
HUME1973
POLLER1995
TABERNER1978
VANGELOVEN1977
VANVROONHOVEN1974
34/58
3/17
15/31
3/48
20/80
9/50
UFH
n/N
RR (fixed)
95% CI
Weight
%
10/19
3/18
8/37
3/49
15/80
1/50
34.05
6.59
16.49
6.71
33.90
2.26
284
253
Total (95% CI)
Total events: 84 (OAC), 40 (UFH)
Test for heterogeneity: Chi² = 6.49, df = 5 (P = 0.26), I² = 22.9%
Test for overall effect: Z = 2.68 (P = 0.007)
100.00
0.01
3
4
5
0.1
1
Favours OAC
10
RR (fixed)
95% CI
1.11
1.06
2.24
1.02
1.33
9.00
[0.69,
[0.25,
[1.10,
[0.22,
[0.74,
[1.18,
1.80]
4.54]
4.57]
4.81]
2.41]
68.42]
1.54 [1.12, 2.12]
100
Favours UFH
Figure 58. OAC vs unfractionated heparin – pulmonary embolism
Review:
VTE Oral anticoagulants and Dextrans
Comparison:05 OAC vs UFH
Outcome: 02 PE
Study
or sub-category
VANGELOVEN1977
OAC
n/N
UFH
n/N
9/80
80
Total (95% CI)
Total events: 9 (OAC), 5 (UFH)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.10 (P = 0.27)
RR (fixed)
95% CI
RR (fixed)
95% CI
5/80
100.00
1.80 [0.63, 5.14]
80
100.00
1.80 [0.63, 5.14]
0.01
6
7
Weight
%
0.1
1
Favours OAC
10
100
Favours UFH
Figure 59. OAC vs unfractionated heparin – proximal DVT
8
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 05 OAC vs UFH
Outcome:
03 Proximal DVT
Study
or sub-category
POLLER1995
OAC
n/N
3/31
31
Total (95% CI)
Total events: 3 (OAC), 0 (UFH)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.42 (P = 0.16)
UFH
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
0/37
100.00
8.31 [0.45, 155.00]
37
100.00
8.31 [0.45, 155.00]
0.01
9
10
Weight
%
0.1
Favours OAC
1
10
100
Favours UFH
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
562 of 648
DRAFT FOR CONSULTATION
1
Figure 60. OAC vs unfractionated heparin – major bleed
Review:
VTE Oral anticoagulants and Dextrans
Comparison:05 OAC vs UFH
Outcome: 04 Major bleed
Study
or sub-category
OAC
n/N
HUME1973
POLLER1995
TABERNER1978
VANGELOVEN1977
UFH
n/N
RR (fixed)
95% CI
1/17
3/47
3/48
1/80
Weight
%
7/18
3/43
5/49
0/80
44.21
20.37
32.17
3.25
192
190
Total (95% CI)
Total events: 8 (OAC), 15 (UFH)
Test for heterogeneity: Chi² = 3.15, df = 3 (P = 0.37), I² = 4.8%
Test for overall effect: Z = 1.46 (P = 0.15)
100.00
0.01
2
3
4
0.1
1
Favours OAC
5
OAC vs LWMH
6
Figure 61. OAC vs LWMH - DVT
10
RR (fixed)
95% CI
0.15
0.91
0.61
3.00
[0.02,
[0.19,
[0.15,
[0.12,
1.10]
4.29]
2.42]
72.56]
0.55 [0.24, 1.23]
100
Favours UFH
Review:
VTE Oral anticoagulants and Dextrans
Comparison:06 OAC vs LMWH
Outcome: 01 DVT
Study
or sub-category
FITZGERALD2001
FRANCIS1997A
FRIEDMAN1994
GERHART1991
HAMULYAK1995
HEIT1997
HULL1993
HULL2000
LECLERC1996
SAMAMA2001
OAC
n/N
80/176
49/190
87/321
28/131
50/257
85/222
231/603
81/363
109/211
20/636
LMWH
n/N
RR (random)
95% CI
Weight
%
44/173
28/192
120/648
9/132
43/260
62/232
185/579
80/712
76/206
15/643
10.62
7.27
12.96
3.25
8.51
11.78
16.76
11.35
13.82
3.68
3110
3777
Total (95% CI)
Total events: 820 (OAC), 662 (LMWH)
Test for heterogeneity: Chi² = 19.13, df = 9 (P = 0.02), I² = 53.0%
Test for overall effect: Z = 5.79 (P < 0.00001)
100.00
0.01
7
8
9
10
11
0.1
Favours OAC
1
10
RR (random)
95% CI
1.79
1.77
1.46
3.13
1.18
1.43
1.20
1.99
1.40
1.35
[1.32,
[1.16,
[1.15,
[1.54,
[0.81,
[1.09,
[1.03,
[1.50,
[1.12,
[0.70,
2.42]
2.69]
1.86]
6.38]
1.70]
1.88]
1.40]
2.63]
1.75]
2.61]
1.51 [1.31, 1.73]
100
Favours LMWH
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
563 of 648
DRAFT FOR CONSULTATION
1
Figure 62. OAC vs LWMH – pulmonary embolism
Review:
VTE Oral anticoagulants and Dextrans
Comparison:06 OAC vs LMWH
Outcome: 02 Pulmonary embolism
Study
or sub-category
COLWELL1999
FITZGERALD2001
FRIEDMAN1994
GERHART1991
HAMULYAK1995
HEIT1997
HULL1993
LECLERC1996
OAC
n/N
LMWH
n/N
RR (fixed)
95% CI
9/1495
0/176
1/321
1/131
0/257
0/222
0/603
3/211
Weight
%
6/1506
0/173
1/648
0/132
0/260
1/232
0/579
1/206
62.16
6.89
5.18
15.25
10.52
3416
3736
Total (95% CI)
Total events: 14 (OAC), 9 (LMWH)
Test for heterogeneity: Chi² = 1.34, df = 4 (P = 0.85), I² = 0%
Test for overall effect: Z = 1.14 (P = 0.25)
100.00
0.01
2
3
4
5
0.1
1
Favours OAC
10
RR (fixed)
95% CI
1.51 [0.54, 4.23]
Not estimable
2.02 [0.13, 32.17]
3.02 [0.12, 73.53]
Not estimable
0.35 [0.01, 8.50]
Not estimable
2.93 [0.31, 27.93]
1.60 [0.72, 3.56]
100
Favours LMWH
Figure 63. OAC vs LWMH – proximal DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 06 OAC vs LMWH
Outcome:
03 Proximal DVT
Study
or sub-category
OAC
n/N
FITZGERALD2001
FRANCIS1997A
FRIEDMAN1994
GERHART1991
HAMULYAK1995
HEIT1997
HULL1993
HULL2000
LECLERC1996
SAMAMA2001
20/176
16/190
33/321
7/131
15/257
15/222
47/603
11/363
22/211
4/636
LMWH
n/N
RR (random)
95% CI
Weight
%
23/173
10/192
41/648
3/132
17/260
15/232
36/579
6/712
24/206
3/643
12.78
7.86
17.88
2.92
9.69
9.26
18.91
5.05
13.31
2.35
3110
3777
Total (95% CI)
Total events: 190 (OAC), 178 (LMWH)
Test for heterogeneity: Chi² = 11.52, df = 9 (P = 0.24), I² = 21.8%
Test for overall effect: Z = 1.86 (P = 0.06)
100.00
0.01
6
7
0.1
Favours OAC
1
10
RR (random)
95% CI
0.85
1.62
1.62
2.35
0.89
1.05
1.25
3.60
0.89
1.35
[0.49,
[0.75,
[1.05,
[0.62,
[0.46,
[0.52,
[0.82,
[1.34,
[0.52,
[0.30,
1.50]
3.47]
2.52]
8.90]
1.75]
2.09]
1.91]
9.65]
1.54]
6.00]
1.25 [0.99, 1.58]
100
Favours LMWH
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
564 of 648
DRAFT FOR CONSULTATION
1
Figure 64. OAC vs LWMH – major bleed
Review:
VTE Oral anticoagulants and Dextrans
Comparison:06 OAC vs LMWH
Outcome: 04 Major bleed
Study
or sub-category
OAC
n/N
COLWELL1999
FITZGERALD2001
FRANCIS1997A
FRIEDMAN1994
GERHART1991
HAMULYAK1995
HEIT1997
HULL1993
HULL2000
LECLERC1996
SAMAMA2001
LMWH
n/N
4/1495
4/176
4/292
21/407
5/145
8/342
12/279
9/721
22/501
6/334
35/645
RR (random)
95% CI
Weight
%
9/1506
9/173
6/288
45/800
8/144
5/330
22/277
20/715
76/1000
7/336
9/644
6.89
7.01
6.40
12.69
7.46
7.36
10.95
10.04
13.08
7.56
10.56
5337
6213
Total (95% CI)
Total events: 130 (OAC), 216 (LMWH)
Test for heterogeneity: Chi² = 27.60, df = 10 (P = 0.002), I² = 63.8%
Test for overall effect: Z = 1.15 (P = 0.25)
0.01
2
3
100.00
0.1
1
Favours OAC
4
OAC vs aspirin
5
Figure 65. OAC vs aspirin - DVT
10
RR (random)
95% CI
0.45
0.44
0.66
0.92
0.62
1.54
0.54
0.45
0.58
0.86
3.88
[0.14,
[0.14,
[0.19,
[0.55,
[0.21,
[0.51,
[0.27,
[0.20,
[0.36,
[0.29,
[1.88,
1.45]
1.39]
2.31]
1.52]
1.85]
4.67]
1.07]
0.97]
0.92]
2.54]
8.01]
0.78 [0.52, 1.19]
100
Favours LMWH
Review:
VTE Oral anticoagulants and Dextrans
Comparison:07 OAC vs aspirin
Outcome: 01 DVT
Study
or sub-category
HARRIS1974
LOTKE1996
POWERS1989
OAC
n/N
AP
n/N
10/55
78/146
13/65
RR (random)
95% CI
Weight
%
0.01
6
7
24.64
46.39
28.97
0.52 [0.26, 1.01]
0.89 [0.73, 1.08]
0.49 [0.28, 0.86]
100.00
0.65 [0.41, 1.04]
18/51
100/166
27/66
266
283
Total (95% CI)
Total events: 101 (OAC), 145 (AP)
Test for heterogeneity: Chi² = 6.01, df = 2 (P = 0.05), I² = 66.7%
Test for overall effect: Z = 1.79 (P = 0.07)
0.1
1
Favours OAC
10
RR (random)
95% CI
100
Favours antiplatelet
Figure 66. OAC vs aspirin – pulmonary embolism
Review:
VTE Oral anticoagulants and Dextrans
Comparison:07 OAC vs aspirin
Outcome: 02 Pulmonary embolism
Study
or sub-category
LOTKE1996
POWERS1989
WOOLSON1991
OAC
n/N
12/146
0/65
0/69
AP
n/N
RR (fixed)
95% CI
Weight
%
0.01
8
83.51
8.30
8.19
0.85 [0.42, 1.74]
0.34 [0.01, 8.16]
0.35 [0.01, 8.39]
100.00
0.77 [0.39, 1.51]
16/166
1/66
1/72
280
304
Total (95% CI)
Total events: 12 (OAC), 18 (AP)
Test for heterogeneity: Chi² = 0.58, df = 2 (P = 0.75), I² = 0%
Test for overall effect: Z = 0.76 (P = 0.45)
0.1
Favours OAC
1
10
RR (fixed)
95% CI
100
Favours antiplatelet
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
565 of 648
DRAFT FOR CONSULTATION
1
Figure 67. OAC vs aspirin – proximal DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison:07 OAC vs aspirin
Outcome: 03 Proximal DVT
Study
or sub-category
OAC
n/N
HARRIS1974
LOTKE1996
POWERS1989
WOOLSON1991
3/55
18/146
6/65
6/69
AP
n/N
RR (fixed)
95% CI
Weight
%
10/51
16/166
7/66
7/72
26.51
38.25
17.74
17.50
335
355
Total (95% CI)
Total events: 33 (OAC), 40 (AP)
Test for heterogeneity: Chi² = 4.69, df = 3 (P = 0.20), I² = 36.1%
Test for overall effect: Z = 0.61 (P = 0.54)
100.00
0.01
0.1
1
2
Favours OAC
3
Figure 68. OAC vs aspirin – major bleed
10
RR (fixed)
95% CI
0.28
1.28
0.87
0.89
[0.08,
[0.68,
[0.31,
[0.32,
0.95]
2.42]
2.45]
2.53]
0.87 [0.57, 1.35]
100
Favours antiplatelet
Review:
VTE Oral anticoagulants and Dextrans
Comparison:07 OAC vs aspirin
Outcome: 04 Major bleed
Study
or sub-category
OAC
n/N
POWERS1989
AP
n/N
5/65
65
Total (95% CI)
Total events: 5 (OAC), 1 (AP)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.50 (P = 0.13)
RR (fixed)
95% CI
Weight
%
RR (fixed)
95% CI
1/66
100.00
5.08 [0.61, 42.28]
66
100.00
5.08 [0.61, 42.28]
0.01
4
5
6
0.1
1
Favours OAC
7
OAC vs dextran
8
Figure 69. OAC vs dextran - DVT
10
100
Favours antiplatelet
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 09 OAC vs dextran
Outcome:
01 DVT
Study
or sub-category
OAC
n/N
BARBER1977
FRANCIS1983
HARRIS1974
LAMBIE1970
MYHRE1969
34/58
11/53
10/55
12/40
9/44
Dextran
n/N
RR (random)
95% CI
Weight
%
26.57
21.52
19.34
14.07
18.50
26/51
19/37
14/62
4/40
11/41
250
231
Total (95% CI)
Total events: 76 (OAC), 74 (Dextran)
Test for heterogeneity: Chi² = 13.82, df = 4 (P = 0.008), I² = 71.1%
Test for overall effect: Z = 0.35 (P = 0.73)
100.00
0.01
9
0.1
Favours OAC
1
10
RR (random)
95% CI
1.15
0.40
0.81
3.00
0.76
[0.81,
[0.22,
[0.39,
[1.06,
[0.35,
1.62]
0.75]
1.66]
8.52]
1.65]
0.91 [0.53, 1.56]
100
Favours Dex
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
566 of 648
DRAFT FOR CONSULTATION
1
Figure 70. OAC vs dextran – pulmonary embolism
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 09 OAC vs dextran
Outcome: 02 Pulmonary embolism
Study
or sub-category
BARBER1977
FRANCIS1983
HARRIS1972
MYHRE1969
OAC
n/N
Dextran
n/N
0/58
0/53
6/114
1/44
RR (fixed)
95% CI
Weight
%
2/51
1/37
7/113
2/11
18.14
12.02
47.99
21.84
269
212
Total (95% CI)
Total events: 7 (OAC), 12 (Dextran)
Test for heterogeneity: Chi² = 3.03, df = 3 (P = 0.39), I² = 1.0%
Test for overall effect: Z = 1.67 (P = 0.10)
100.00
0.01
2
3
0.1
1
Favours OAC
10
RR (fixed)
95% CI
0.18
0.23
0.85
0.13
[0.01,
[0.01,
[0.29,
[0.01,
3.59]
5.60]
2.45]
1.26]
0.50 [0.22, 1.13]
100
Favours Dex
Figure 71. OAC vs dextran – proximal DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison:09 OAC vs dextran
Outcome: 03 Proximal DVT
Study
or sub-category
FRANCIS1983
HARRIS1974
OAC
n/N
Dextran
n/N
1/53
3/55
RR (random)
95% CI
RR (random)
95% CI
6/37
8/62
29.45
70.55
0.12 [0.01, 0.93]
0.42 [0.12, 1.51]
108
99
Total (95% CI)
Total events: 4 (OAC), 14 (Dextran)
Test for heterogeneity: Chi² = 1.10, df = 1 (P = 0.29), I² = 8.9%
Test for overall effect: Z = 2.09 (P = 0.04)
100.00
0.29 [0.09, 0.93]
0.01
4
5
Weight
%
0.1
1
Favours OAC
10
100
Favours Dex
Figure 72. OAC vs dextran – major bleed
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 09 OAC vs dextran
Outcome:
04 Major bleed
Study
or sub-category
FRANCIS1983
HARRIS1972
OAC
n/N
2/57
4/114
Dextran
n/N
RR (fixed)
95% CI
Weight
%
1/43
0/113
171
156
Total (95% CI)
Total events: 6 (OAC), 1 (Dextran)
Test for heterogeneity: Chi² = 0.91, df = 1 (P = 0.34), I² = 0%
Test for overall effect: Z = 1.52 (P = 0.13)
0.01
6
7
8
0.1
Favours OAC
1
10
RR (fixed)
95% CI
69.42
30.58
1.51 [0.14, 16.10]
8.92 [0.49, 163.81]
100.00
3.78 [0.68, 21.04]
100
Favours Dex
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
567 of 648
DRAFT FOR CONSULTATION
1
OAC vs danaparoid
2
Figure 73. OAC vs danaparoid - DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 10 OAC vs Danaparoid
Outcome:
01 DVT
Study
or sub-category
OAC
n/N
COMP1998
GERHART1991
53/197
36/131
Heparinoid
n/N
RR (fixed)
95% CI
Weight
%
29/199
13/132
328
331
Total (95% CI)
Total events: 89 (OAC), 42 (Heparinoid)
Test for heterogeneity: Chi² = 1.29, df = 1 (P = 0.26), I² = 22.5%
Test for overall effect: Z = 4.46 (P < 0.00001)
0.01
3
4
0.1
1
Favours OAC
10
RR (fixed)
95% CI
69.02
30.98
1.85 [1.23, 2.78]
2.79 [1.55, 5.02]
100.00
2.14 [1.53, 2.99]
100
Favours heparinoid
Figure 74. OAC vs danaparoid – pulmonary embolism
Review:
VTE Oral anticoagulants and Dextrans
Comparison:10 OAC vs Danaparoid
Outcome: 02 Pulmonary embolism
Study
or sub-category
COMP1998
GERHART1991
OAC
n/N
Heparinoid
n/N
1/197
1/131
RR (fixed)
95% CI
Weight
%
0/199
0/132
328
331
Total (95% CI)
Total events: 2 (OAC), 0 (Heparinoid)
Test for heterogeneity: Chi² = 0.00, df = 1 (P = 1.00), I² = 0%
Test for overall effect: Z = 0.96 (P = 0.34)
0.01
5
6
0.1
1
Favours OAC
10
RR (fixed)
95% CI
49.97
50.03
3.03 [0.12, 73.94]
3.02 [0.12, 73.53]
100.00
3.03 [0.32, 28.94]
100
Favours heparinoid
Figure 75. OAC vs danaparoid – proximal DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 10 OAC vs Danaparoid
Outcome:
03 Proximal DVT
Study
or sub-category
COMP1998
OAC
n/N
8/197
197
Total (95% CI)
Total events: 8 (OAC), 3 (Heparinoid)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.48 (P = 0.14)
Heparinoid
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
3/199
100.00
2.69 [0.73, 10.01]
199
100.00
2.69 [0.73, 10.01]
0.01
7
Weight
%
0.1
Favours OAC
1
10
100
Favours heparinoid
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
568 of 648
DRAFT FOR CONSULTATION
1
Figure 76. OAC vs danaparoid – major bleed
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 10 OAC vs Danaparoid
Outcome:
04 Major bleed
Study
or sub-category
COMP1998
GERHART1991
OAC
n/N
Heparinoid
n/N
7/247
5/131
RR (fixed)
95% CI
Weight
%
7/241
8/132
378
373
Total (95% CI)
Total events: 12 (OAC), 15 (Heparinoid)
Test for heterogeneity: Chi² = 0.33, df = 1 (P = 0.57), I² = 0%
Test for overall effect: Z = 0.61 (P = 0.54)
0.01
2
3
0.1
1
Favours OAC
10
RR (fixed)
95% CI
47.07
52.93
0.98 [0.35, 2.74]
0.63 [0.21, 1.87]
100.00
0.79 [0.38, 1.67]
100
Favours heparinoid
4
Danaparoid vs no prophylaxis
5
Figure 77. Danaparoid vs no prophylaxis - DVT
Review:
VTE Danaparoid
Comparison: 01 Danaparoid vs no prophylaxis
Outcome: 01 DVT
Study
or sub-category
HOEK1992
Treatment
n/N
15/97
Control
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
56/99
100.00
0.27 [0.17, 0.45]
99
100.00
0.27 [0.17, 0.45]
97
Total (95% CI)
Total events: 15 (Treatment), 56 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 5.12 (P < 0.00001)
0.01
6
7
8
Weight
%
0.1
1
Favours treatment
10
100
Favours control
Figure 78. Danaparoid vs no prophylaxis – pulmonary embolism
Review:
VTE Danaparoid
Comparison: 01 Danaparoid vs no prophylaxis
Outcome: 02 Pulmonary embolism
Study
or sub-category
HOEK1992
Treatment
n/N
0/97
0
Total (95% CI)
Total events: 0 (Treatment), 0 (Control)
Test for heterogeneity: not applicable
Test for overall effect: not applicable
Control
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
0/99
Not estimable
0
Not estimable
0.01
9
10
Weight
%
0.1
Favours treatment
1
10
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
569 of 648
DRAFT FOR CONSULTATION
1
Figure 79. Danaparoid vs no prophylaxis – proximal DVT
Review:
VTE Danaparoid
Comparison:01 Danaparoid vs no prophylaxis
Outcome: 03 Proximal DVT
Study
or sub-category
HOEK1992
Treatment
n/N
8/97
Control
n/N
RR (fixed)
95% CI
Weight
%
RR (fixed)
95% CI
25/99
100.00
0.33 [0.16, 0.69]
99
100.00
0.33 [0.16, 0.69]
97
Total (95% CI)
Total events: 8 (Treatment), 25 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 2.94 (P = 0.003)
0.01
2
0.1
1
Favours treatment
3
Danaparoid vs dextran
4
Figure 80. Danaparoid vs dextran - DVT
10
100
Favours control
Review:
VTE Danaparoid
Comparison:02 Danaparoid vs Dextran 70
Outcome: 01 DVT
Study
or sub-category
BERGQVIST1991
Treatment
n/N
14/107
Control
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
40/115
100.00
0.38 [0.22, 0.65]
115
100.00
0.38 [0.22, 0.65]
107
Total (95% CI)
Total events: 14 (Treatment), 40 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 3.49 (P = 0.0005)
0.01
5
6
Weight
%
0.1
1
Favours treatment
10
100
Favours control
Figure 81. Danaparoid vs dextran – pulmonary embolism
Review:
VTE Danaparoid
Comparison:02 Danaparoid vs Dextran 70
Outcome: 02 Pulmonary embolism
Study
or sub-category
BERGQVIST1991
Treatment
n/N
1/117
117
Total (95% CI)
Total events: 1 (Treatment), 2 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.48 (P = 0.63)
Control
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
2/130
100.00
0.56 [0.05, 6.05]
130
100.00
0.56 [0.05, 6.05]
0.01
7
8
9
10
Weight
%
0.1
Favours treatment
1
10
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
570 of 648
DRAFT FOR CONSULTATION
1
Danaparoid vs low molecular weight heparin (LMWH)
2
Figure 82. Danaparoid vs LMWH - DVT
Review:
VTE Danaparoid
Comparison:07 Danaparoid vs LMWH
Outcome: 01 DVT
Study
or sub-category
BERGQVIST1999A
Treatment
n/N
3/53
Control
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
13/109
100.00
0.47 [0.14, 1.59]
109
100.00
0.47 [0.14, 1.59]
53
Total (95% CI)
Total events: 3 (Treatment), 13 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.21 (P = 0.23)
0.01
3
4
Weight
%
0.1
1
Favours treatment
10
100
Favours control
Figure 83. Danaparoid vs LMWH – pulmonary embolism
Review:
VTE Danaparoid
Comparison:07 Danaparoid vs LMWH
Outcome: 02 Pulmonary embolism
Study
or sub-category
BERGQVIST1999A
Treatment
n/N
Control
n/N
0/65
0
Total (95% CI)
Total events: 0 (Treatment), 0 (Control)
Test for heterogeneity: not applicable
Test for overall effect: not applicable
RR (fixed)
95% CI
7
RR (fixed)
95% CI
0/132
Not estimable
0
Not estimable
0.01
5
6
Weight
%
0.1
1
Favours treatment
10
100
Favours control
Figure 84. Danaparoid vs LMWH – proximal DVT
Review:
VTE Danaparoid
Comparison:07 Danaparoid vs LMWH
Outcome: 03 Proximal DVT
Study
or sub-category
BERGQVIST1999A
Treatment
n/N
2/53
53
Total (95% CI)
Total events: 2 (Treatment), 5 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.24 (P = 0.81)
Control
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
5/109
100.00
0.82 [0.16, 4.10]
109
100.00
0.82 [0.16, 4.10]
0.01
8
Weight
%
0.1
Favours treatment
1
10
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
571 of 648
DRAFT FOR CONSULTATION
1
Figure 85. Danaparoid vs LMWH – major bleed
Review:
VTE Danaparoid
Comparison:07 Danaparoid vs LMWH
Outcome: 04 Major bleed
Study
or sub-category
BERGQVIST1999A
Treatment
n/N
Control
n/N
1/65
65
Total (95% CI)
Total events: 1 (Treatment), 3 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.34 (P = 0.73)
RR (fixed)
95% CI
RR (fixed)
95% CI
3/132
100.00
0.68 [0.07, 6.38]
132
100.00
0.68 [0.07, 6.38]
0.01
2
3
Weight
%
0.1
1
Favours treatment
10
100
Favours control
4
Danaparoid vs unfractionated heparin
5
Figure 86. Danaparoid vs unfractionated heparin - DVT
Review:
VTE Danaparoid
Comparison: 05 Danaparoid vs UFH
Outcome: 01 DVT
Study
or sub-category
Danaparoid
n/N
GALLUS1993
LEYVRAZ1992
25/241
25/145
UFH
n/N
RR (fixed)
95% CI
Weight
%
37/249
44/139
386
388
Total (95% CI)
Total events: 50 (Danaparoid), 81 (UFH)
Test for heterogeneity: Chi² = 0.57, df = 1 (P = 0.45), I² = 0%
Test for overall effect: Z = 3.00 (P = 0.003)
0.01
0.1
1
10
RR (fixed)
95% CI
44.75
55.25
0.70 [0.43, 1.12]
0.54 [0.35, 0.84]
100.00
0.61 [0.45, 0.84]
100
6
Favours Danaparoid
7
Figure 87. Danaparoid vs unfractionated heparin – pulmonary embolism
Favours UFH
Review:
VTE Danaparoid
Comparison: 05 Danaparoid vs UFH
Outcome: 02 PE
Study
or sub-category
Danaparoid
n/N
GALLUS1993
LEYVRAZ1992
1/241
1/145
UFH
n/N
RR (fixed)
95% CI
Weight
%
0/249
1/139
386
388
Total (95% CI)
Total events: 2 (Danaparoid), 1 (UFH)
Test for heterogeneity: Chi² = 0.30, df = 1 (P = 0.59), I² = 0%
Test for overall effect: Z = 0.49 (P = 0.62)
0.01
8
0.1
Favours Danaparoid
1
10
RR (fixed)
95% CI
32.51
67.49
3.10 [0.13, 75.71]
0.96 [0.06, 15.18]
100.00
1.65 [0.22, 12.33]
100
Favours UFH
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
572 of 648
DRAFT FOR CONSULTATION
1
Figure 88. Danaparoid vs unfractionated heparin – proximal DVT
Review:
VTE Danaparoid
Comparison: 05 Danaparoid vs UFH
Outcome: 03 Proximal DVT
Study
or sub-category
Danaparoid
n/N
LEYVRAZ1992
7/145
UFH
n/N
RR (fixed)
95% CI
145
Total (95% CI)
Total events: 7 (Danaparoid), 9 (UFH)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.60 (P = 0.55)
RR (fixed)
95% CI
9/139
100.00
0.75 [0.29, 1.95]
139
100.00
0.75 [0.29, 1.95]
0.01
2
Weight
%
0.1
1
Favours Danaparoid
3
Danaparoid vs aspirin
4
Figure 89. Danaparoid vs aspirin - DVT
10
100
Favours UFH
Review:
VTE Danaparoid
Comparison:06 Danaparoid vs aspirin
Outcome: 01 DVT
Study
or sub-category
GENT1996
Treatment
n/N
Control
n/N
25/90
90
Total (95% CI)
Total events: 25 (Treatment), 38 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 2.11 (P = 0.04)
RR (fixed)
95% CI
6
RR (fixed)
95% CI
38/88
100.00
0.64 [0.43, 0.97]
88
100.00
0.64 [0.43, 0.97]
0.01
5
Weight
%
0.1
1
Favours treatment
10
100
Favours control
Figure 90. Danaparoid vs aspirin – pulmonary embolism
Review:
VTE Danaparoid
Comparison:06 Danaparoid vs aspirin
Outcome: 02 Pulmonary embolism
Study
or sub-category
GENT1996
Treatment
n/N
Control
n/N
0/125
125
Total (95% CI)
Total events: 0 (Treatment), 1 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.67 (P = 0.50)
RR (fixed)
95% CI
8
RR (fixed)
95% CI
1/126
100.00
0.34 [0.01, 8.17]
126
100.00
0.34 [0.01, 8.17]
0.01
7
Weight
%
0.1
1
Favours treatment
10
100
Favours control
Figure 91. Danaparoid vs aspirin – proximal DVT
Review:
VTE Danaparoid
Comparison:06 Danaparoid vs aspirin
Outcome: 03 Proximal DVT
Study
or sub-category
GENT1996
Treatment
n/N
6/88
88
Total (95% CI)
Total events: 6 (Treatment), 11 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.37 (P = 0.17)
Control
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
11/83
100.00
0.51 [0.20, 1.33]
83
100.00
0.51 [0.20, 1.33]
0.01
9
Weight
%
0.1
Favours treatment
1
10
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
573 of 648
DRAFT FOR CONSULTATION
1
Dextran vs no prophylaxis
2
Figure 92. Dextran vs no prophylaxis – DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison:30 Dextran vs no prophylaxis
Outcome: 01 DVT
Study
or sub-category
BERGQVIST1980
BERGQVST1979
BONNAR1974
CARTER1973
EVARTS1971
GRUBER1977A
HEFLEY1990
HUBENS1976
HURSON1979
HUTTUNEN1977
JOHNSSON1968
MACINTYRE1974
STEPHENSON1973
VONHOSPENTHAL1997
WELINBERGER1982
Dextrans
n/N
Control
n/N
15/52
13/27
1/120
1/106
4/18
20/92
15/45
5/39
15/55
52/150
1/27
32/128
10/34
3/39
4/16
RR (random)
95% CI
Weight
%
14/51
20/22
15/140
10/101
10/21
36/100
14/42
9/41
9/51
25/75
13/25
47/128
16/46
2/47
5/18
8.60
11.39
1.63
1.59
5.18
10.61
8.88
4.98
7.27
11.76
1.71
11.93
8.15
2.11
4.21
948
908
Total (95% CI)
Total events: 191 (Dextrans), 245 (Control)
Test for heterogeneity: Chi² = 29.73, df = 14 (P = 0.008), I² = 52.9%
Test for overall effect: Z = 2.36 (P = 0.02)
0.01
3
4
5
100.00
0.1
1
Favours Dextrans
10
RR (random)
95% CI
1.05
0.53
0.08
0.10
0.47
0.60
1.00
0.58
1.55
1.04
0.07
0.68
0.85
1.81
0.90
[0.57,
[0.35,
[0.01,
[0.01,
[0.18,
[0.38,
[0.55,
[0.21,
[0.74,
[0.71,
[0.01,
[0.47,
[0.44,
[0.32,
[0.29,
1.95]
0.80]
0.58]
0.73]
1.24]
0.96]
1.81]
1.59]
3.22]
1.53]
0.51]
0.99]
1.63]
10.28]
2.78]
0.72 [0.55, 0.95]
100
Favours control
Figure 93. Dextran vs no prophylaxis – pulmonary embolism
Review:
VTE Oral anticoagulants and Dextrans
Comparison:30 Dextran vs no prophylaxis
Outcome: 02 Pulmonary embolism
Study
or sub-category
HURSON1979
WELINBERGER1982
Dextrans
n/N
8/55
0/16
Control
n/N
RR (fixed)
95% CI
Weight
%
9/51
1/18
71
69
Total (95% CI)
Total events: 8 (Dextrans), 10 (Control)
Test for heterogeneity: Chi² = 0.23, df = 1 (P = 0.63), I² = 0%
Test for overall effect: Z = 0.63 (P = 0.53)
0.01
6
7
0.1
Favours Dextran
1
10
RR (fixed)
95% CI
86.83
13.17
0.82 [0.34, 1.97]
0.37 [0.02, 8.55]
100.00
0.76 [0.33, 1.77]
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
574 of 648
DRAFT FOR CONSULTATION
1
Figure 94. Dextran vs no prophylaxis – proximal DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison:30 Dextran vs no prophylaxis
Outcome: 03 Proximal DVT
Study
or sub-category
BERGQVIST1980
BONNAR1974
GRUBER1977A
HUBENS1976
HURSON1979
WELINBERGER1982
Dextrans
n/N
Control
n/N
10/52
0/120
0/92
1/39
5/55
3/16
RR (random)
95% CI
Weight
%
8/51
4/150
4/100
2/41
7/51
2/18
43.74
4.29
4.30
6.47
28.37
12.83
374
411
Total (95% CI)
Total events: 19 (Dextrans), 27 (Control)
Test for heterogeneity: Chi² = 5.27, df = 5 (P = 0.38), I² = 5.1%
Test for overall effect: Z = 0.57 (P = 0.57)
100.00
0.01
2
3
4
0.1
1
Favours Dextrans
10
RR (random)
95% CI
1.23
0.14
0.12
0.53
0.66
1.69
[0.53,
[0.01,
[0.01,
[0.05,
[0.22,
[0.32,
2.86]
2.55]
2.21]
5.57]
1.96]
8.85]
0.84 [0.46, 1.54]
100
Favours control
Figure 95. Dextran vs no prophylaxis – major bleed
Review:
VTE Oral anticoagulants and Dextrans
Comparison:30 Dextran vs no prophylaxis
Outcome: 04 Major bleed
Study
or sub-category
BERGQVIST1980
BERGQVST1979
HUBENS1976
JOHNSSON1968
VONHOSPENTHAL1997
Dextrans
n/N
Control
n/N
0/57
0/27
0/39
0/27
0/40
0
Total (95% CI)
Total events: 0 (Dextrans), 0 (Control)
Test for heterogeneity: not applicable
Test for overall effect: not applicable
RR (random)
95% CI
RR (random)
95% CI
0/58
0/22
0/41
0/25
0/49
Not
Not
Not
Not
Not
0
Not estimable
0.01
5
6
Weight
%
0.1
1
Favours Dextrans
7
Dextran as an adjuvant intervention
8
Figure 96. Dextran adjuvant – DVT
10
estimable
estimable
estimable
estimable
estimable
100
Favours control
Review:
VTE Oral anticoagulants and Dextrans
Comparison:31 Dextran as an adjuvant intervention
Outcome: 01 DVT
Study
or sub-category
ANDERSON1986
SCHONDORF1980
SMITH1978
SWIERSTRA1984
VANGELOVEN1977
Dextran
n/N
Control
n/N
RR (fixed)
95% CI
14/31
8/55
36/95
34/81
20/80
12.36
7.24
33.23
29.01
18.15
330
342
Total (95% CI)
Total events: 62 (Dextran), 112 (Control)
Test for heterogeneity: Chi² = 4.81, df = 4 (P = 0.31), I² = 16.9%
Test for overall effect: Z = 3.99 (P < 0.0001)
100.00
5/29
9/54
18/97
21/71
9/79
0.01
9
10
Weight
%
0.1
Favours Dextran
1
10
RR (fixed)
95% CI
0.38
1.15
0.49
0.70
0.46
[0.16,
[0.48,
[0.30,
[0.45,
[0.22,
0.93]
2.75]
0.80]
1.10]
0.94]
0.58 [0.44, 0.76]
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
575 of 648
DRAFT FOR CONSULTATION
1
Figure 97. Dextran adjuvant – pulmonary embolism
Review:
VTE Oral anticoagulants and Dextrans
Comparison:31 Dextran as an adjuvant intervention
Outcome: 02 Pulmonary embolism
Study
or sub-category
SCHONDORF1980
SMITH1978
VANGELOVEN1977
Dextran
n/N
Control
n/N
1/54
3/97
4/79
RR (fixed)
95% CI
Weight
%
0.01
2
3
12.40
31.62
55.98
0.51 [0.05, 5.45]
0.59 [0.14, 2.39]
0.45 [0.14, 1.40]
100.00
0.50 [0.22, 1.14]
2/55
5/95
9/80
230
230
Total (95% CI)
Total events: 8 (Dextran), 16 (Control)
Test for heterogeneity: Chi² = 0.08, df = 2 (P = 0.96), I² = 0%
Test for overall effect: Z = 1.64 (P = 0.10)
0.1
1
Favours dextran
10
RR (fixed)
95% CI
100
Favours control
Figure 98. Dextran adjuvant –proximal DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison:31 Dextran as an adjuvant intervention
Outcome: 03 Proximal DVT
Study
or sub-category
SWIERSTRA1984
Dextran
n/N
Control
n/N
14/71
71
Total (95% CI)
Total events: 14 (Dextran), 23 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.23 (P = 0.22)
RR (fixed)
95% CI
6
RR (fixed)
95% CI
23/81
100.00
0.69 [0.39, 1.24]
81
100.00
0.69 [0.39, 1.24]
0.01
4
5
Weight
%
0.1
1
Favours Dextran
10
100
Favours control
Figure 99. Dextran adjuvant – major bleed
Review:
VTE Oral anticoagulants and Dextrans
Comparison:31 Dextran as an adjuvant intervention
Outcome: 04 Major bleed
Study
or sub-category
SCHONDORF1980
SWIERSTRA1984
VANGELOVEN1977
Dextran
n/N
0/54
17/71
2/79
Control
n/N
RR (fixed)
95% CI
Weight
%
0/55
8/81
1/80
88.26
11.74
204
216
Total (95% CI)
Total events: 19 (Dextran), 9 (Control)
Test for heterogeneity: Chi² = 0.02, df = 1 (P = 0.89), I² = 0%
Test for overall effect: Z = 2.30 (P = 0.02)
0.01
7
8
100.00
0.1
Favours dextran
1
10
RR (fixed)
95% CI
Not estimable
2.42 [1.11, 5.28]
2.03 [0.19, 21.89]
2.38 [1.13, 4.98]
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
576 of 648
DRAFT FOR CONSULTATION
1
2
Dextran vs no prophylaxis – subgrouped by Dextran 40 and
Dextran 70
3
Figure 100. Dextran vs no prophylaxis – subgrouped by Dextran 40 and
4
Dextran 70 – DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 35 Dextran vs no prophylaxis - subgroup analysis comparing Dextran 40 and Dextran 70
Outcome:
01 DVT
Study
or sub-category
Dextran
n/N
Control
n/N
RR (random)
95% CI
Weight
%
01 Dextran 40
20/92
36/100
GRUBER1977A
15/45
14/42
HEFLEY1990
5/39
9/41
HUBENS1976
176
183
Subtotal (95% CI)
Total events: 40 (Dextran), 59 (Control)
Test for heterogeneity: Chi² = 1.89, df = 2 (P = 0.39), I² = 0%
Test for overall effect: Z = 1.92 (P = 0.05)
02 Dextran 70
15/52
14/51
BERGQVIST1980
13/27
20/22
BERGQVST1979
1/120
15/140
BONNAR1974
1/106
10/101
CARTER1973
15/55
9/51
HURSON1979
1/27
13/25
JOHNSSON1968
32/128
47/128
MACINTYRE1974
10/34
16/46
STEPHENSON1973
3/39
2/47
VONHOSPENTHAL1997
4/16
5/18
WELINBERGER1982
604
629
Subtotal (95% CI)
Total events: 95 (Dextran), 151 (Control)
Test for heterogeneity: Chi² = 23.96, df = 9 (P = 0.004), I² = 62.4%
Test for overall effect: Z = 1.84 (P = 0.07)
780
812
Total (95% CI)
Total events: 135 (Dextran), 210 (Control)
Test for heterogeneity: Chi² = 25.67, df = 12 (P = 0.01), I² = 53.2%
Test for overall effect: Z = 2.27 (P = 0.02)
5
6
7
12.58
10.66
6.16
29.40
0.60
1.00
0.58
0.71
[0.38,
[0.55,
[0.21,
[0.50,
0.96]
1.81]
1.59]
1.01]
10.34
13.44
2.07
2.02
8.83
2.16
14.01
9.84
2.66
5.23
70.60
1.05
0.53
0.08
0.10
1.55
0.07
0.68
0.85
1.81
0.90
0.67
[0.57,
[0.35,
[0.01,
[0.01,
[0.74,
[0.01,
[0.47,
[0.44,
[0.32,
[0.29,
[0.44,
1.95]
0.80]
0.58]
0.73]
3.22]
0.51]
0.99]
1.63]
10.28]
2.78]
1.03]
100.00
0.01
0.1
Favours Dextran
1
10
RR (random)
95% CI
0.70 [0.52, 0.95]
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
577 of 648
DRAFT FOR CONSULTATION
1
Figure 101. Dextran vs no prophylaxis – subgrouped by molecular
2
weight – proximal DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 35 Dextran vs no prophylaxis - subgroup analysis comparing Dextran 40 and Dextran 70
Outcome:
02 Proximal DVT
Study
or sub-category
Dextrans
n/N
Control
n/N
RR (random)
95% CI
Weight
%
01 Dextran 40
0/92
4/100
GRUBER1977A
1/39
2/41
HUBENS1976
131
141
Subtotal (95% CI)
Total events: 1 (Dextrans), 6 (Control)
Test for heterogeneity: Chi² = 0.63, df = 1 (P = 0.43), I² = 0%
Test for overall effect: Z = 1.31 (P = 0.19)
02 Dextran 70
10/52
8/51
BERGQVIST1980
0/120
4/150
BONNAR1974
5/55
7/51
HURSON1979
3/16
2/18
WELINBERGER1982
243
270
Subtotal (95% CI)
Total events: 18 (Dextrans), 21 (Control)
Test for heterogeneity: Chi² = 3.02, df = 3 (P = 0.39), I² = 0.7%
Test for overall effect: Z = 0.13 (P = 0.89)
374
411
Total (95% CI)
Total events: 19 (Dextrans), 27 (Control)
Test for heterogeneity: Chi² = 5.27, df = 5 (P = 0.38), I² = 5.1%
Test for overall effect: Z = 0.57 (P = 0.57)
4.30
6.47
10.77
0.12 [0.01, 2.21]
0.53 [0.05, 5.57]
0.29 [0.05, 1.83]
43.74
4.29
28.37
12.83
89.23
1.23
0.14
0.66
1.69
0.96
100.00
0.01
3
0.1
1
Favours Dextrans
4
Dextran vs LMWH
5
Figure 102. Dextran vs LMWH – DVT
10
RR (random)
95% CI
[0.53,
[0.01,
[0.22,
[0.32,
[0.52,
2.86]
2.55]
1.96]
8.85]
1.76]
0.84 [0.46, 1.54]
100
Favours control
Review:
VTE Oral anticoagulants and Dextrans
Comparison:33 Dextran vs LMWH
Outcome: 01 DVT
Study
or sub-category
DANENOX1991
ERIKSSON1988
MATZCH1991
OERTLI1992
WIIG1995
Dextran
n/N
24/111
22/49
36/108
31/95
38/134
LMWH
n/N
RR (random)
95% CI
Weight
%
13.71
17.63
22.91
20.50
25.25
7/108
10/49
22/111
16/103
35/128
497
499
Total (95% CI)
Total events: 151 (Dextran), 90 (LMWH)
Test for heterogeneity: Chi² = 10.08, df = 4 (P = 0.04), I² = 60.3%
Test for overall effect: Z = 3.00 (P = 0.003)
0.01
6
7
100.00
0.1
Favours Dextran
1
10
RR (random)
95% CI
3.34
2.20
1.68
2.10
1.04
[1.50,
[1.17,
[1.06,
[1.23,
[0.70,
7.42]
4.15]
2.66]
3.59]
1.53]
1.79 [1.22, 2.63]
100
Favours LMWH
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
578 of 648
DRAFT FOR CONSULTATION
1
Figure 103. Dextran vs LMWH – pulmonary embolism
Review:
VTE Oral anticoagulants and Dextrans
Comparison:33 Dextran vs LMWH
Outcome: 02 Pulmonary embolism
Study
or sub-category
ERIKSSON1988
MATZCH1991
OERTLI1992
WIIG1995
Dextran
n/N
LMWH
n/N
RR (fixed)
95% CI
2/49
4/108
1/95
0/134
Weight
%
2/49
2/111
2/103
0/128
33.95
33.48
32.57
386
391
Total (95% CI)
Total events: 7 (Dextran), 6 (LMWH)
Test for heterogeneity: Chi² = 0.86, df = 2 (P = 0.65), I² = 0%
Test for overall effect: Z = 0.34 (P = 0.74)
100.00
0.01
2
3
0.1
1
Favours Dextran
10
RR (fixed)
95% CI
1.00 [0.15, 6.82]
2.06 [0.38, 10.99]
0.54 [0.05, 5.88]
Not estimable
1.20 [0.41, 3.54]
100
Favours LMWH
Figure 104. Dextran vs LMWH – proximal DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 33 Dextran vs LMWH
Outcome:
03 Proximal DVT
Study
or sub-category
DANENOX1991
ERIKSSON1988
MATZCH1991
OERTLI1992
WIIG1995
Dextran
n/N
LMWH
n/N
6/111
3/49
2/108
1/95
0/134
RR (random)
95% CI
Weight
%
32.67
12.57
24.49
17.83
12.45
2/108
0/49
2/111
2/103
3/128
497
499
Total (95% CI)
Total events: 12 (Dextran), 9 (LMWH)
Test for heterogeneity: Chi² = 5.08, df = 4 (P = 0.28), I² = 21.3%
Test for overall effect: Z = 0.43 (P = 0.67)
100.00
0.01
4
5
6
7
8
9
0.1
1
Favours Dextran
10
RR (random)
95% CI
2.92
7.00
1.03
0.54
0.14
[0.60,
[0.37,
[0.15,
[0.05,
[0.01,
14.15]
132.03]
7.17]
5.88]
2.62]
1.28 [0.42, 3.91]
100
Favours LMWH
Figure 105. Dextran vs LMWH – major bleed
Review:
VTE Oral anticoagulants and Dextrans
Comparison:33 Dextran vs LMWH
Outcome: 04 Major bleed
Study
or sub-category
ERIKSSON1988
MATZCH1991
OERTLI1992
WIIG1995
Dextran
n/N
0/51
0/123
0/103
0/164
0
Total (95% CI)
Total events: 0 (Dextran), 0 (LMWH)
Test for heterogeneity: not applicable
Test for overall effect: not applicable
LMWH
n/N
RR (random)
95% CI
RR (random)
95% CI
0/50
0/120
0/113
0/165
Not
Not
Not
Not
0
Not estimable
0.01
10
11
Weight
%
0.1
Favours Dextran
1
10
estimable
estimable
estimable
estimable
100
Favours LMWH
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
579 of 648
DRAFT FOR CONSULTATION
1
Dextran vs UFH
2
Figure 106. Dextran vs UFH – DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison:32 Dextran vs UFH
Outcome: 01 DVT
Study
or sub-category
BARBER1977
BERGQVIST1980
BERGQVST1979
FREDIN1983
GRUBER1977A
HOHL1980
HUBENS1976
MACINTYRE1974
MCCARTHY1974
URBANYI1982
VANGELOVEN1977
WELINBERGER1982
WILLEJORGENSEN1991
Dextran
n/N
LDUH
n/N
26/51
15/52
13/27
49/114
20/92
17/117
5/39
32/128
11/68
2/46
9/79
4/16
13/85
RR (random)
95% CI
Weight
%
10/19
6/46
18/28
41/93
12/94
2/115
4/39
15/125
7/64
1/43
13/74
8/17
2/79
11.11
7.57
11.38
13.10
9.50
4.02
4.97
10.49
7.36
1.80
8.20
6.55
3.96
914
836
Total (95% CI)
Total events: 216 (Dextran), 139 (LDUH)
Test for heterogeneity: Chi² = 32.20, df = 12 (P = 0.001), I² = 62.7%
Test for overall effect: Z = 1.61 (P = 0.11)
0.01
3
4
100.00
0.1
1
10
Favours Dextran
RR (random)
95% CI
0.97
2.21
0.75
0.97
1.70
8.35
1.25
2.08
1.48
1.87
0.65
0.53
6.04
[0.58,
[0.94,
[0.46,
[0.71,
[0.88,
[1.97,
[0.36,
[1.19,
[0.61,
[0.18,
[0.29,
[0.20,
[1.41,
1.60]
5.22]
1.21]
1.33]
3.28]
35.35]
4.31]
3.65]
3.58]
19.88]
1.43]
1.43]
25.93]
1.32 [0.94, 1.85]
100
Favours LDUH
Figure 107. Dextran vs UFH – pulmonary embolism
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 32 Dextran vs UFH
Outcome: 02 Pulmonary embolism
Study
or sub-category
FREDIN1983
URBANYI1982
VANGELOVEN1977
WELINBERGER1982
WILLEJORGENSEN1991
Dextran
n/N
LDUH
n/N
22/114
0/46
4/79
0/16
1/85
RR (fixed)
95% CI
Weight
%
87.66
20/93
0/43
2/74
0/17
1/79
8.22
4.12
340
306
Total (95% CI)
Total events: 27 (Dextran), 23 (LDUH)
Test for heterogeneity: Chi² = 0.68, df = 2 (P = 0.71), I² = 0%
Test for overall effect: Z = 0.08 (P = 0.93)
100.00
0.01
5
6
7
0.1
1
Favours Dextran
10
RR (fixed)
95% CI
0.90 [0.52, 1.54]
Not estimable
1.87 [0.35, 9.93]
Not estimable
0.93 [0.06, 14.61]
0.98 [0.59, 1.62]
100
Favours LDUH
Figure 108. Dextran vs UFH – proximal DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison: 32 Dextran vs UFH
Outcome:
03 Proximal DVT
Study
or sub-category
BERGQVIST1980
GRUBER1977A
HOHL1980
HUBENS1976
WELINBERGER1982
Dextran
n/N
10/52
0/92
3/117
1/39
3/16
LDUH
n/N
RR (random)
95% CI
Weight
%
43.18
6.40
12.87
6.47
31.07
3/46
1/94
1/115
0/39
3/17
316
311
Total (95% CI)
Total events: 17 (Dextran), 8 (LDUH)
Test for heterogeneity: Chi² = 2.46, df = 4 (P = 0.65), I² = 0%
Test for overall effect: Z = 1.52 (P = 0.13)
100.00
0.01
8
0.1
Favours Dextran
1
10
RR (random)
95% CI
2.95
0.34
2.95
3.00
1.06
[0.86,
[0.01,
[0.31,
[0.13,
[0.25,
10.07]
8.25]
27.93]
71.46]
4.52]
1.87 [0.84, 4.19]
100
Favours LDUH
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
580 of 648
DRAFT FOR CONSULTATION
1
Figure 109. Dextran vs UFH – major bleed
Review:
VTE Oral anticoagulants and Dextrans
Comparison:32 Dextran vs UFH
Outcome: 04 Major bleed
Study
or sub-category
BERGQVIST1980
BERGQVST1979
GRUBER1977A
HUBENS1976
MACINTYRE1974
URBANYI1982
VANGELOVEN1977
WILLEJORGENSEN1991
Dextran
n/N
LDUH
n/N
RR (fixed)
95% CI
0/57
0/27
1/113
0/39
0/130
0/46
2/79
1/98
Weight
%
0/58
0/28
8/119
0/39
1/128
0/46
2/74
0/94
65.60
12.72
17.38
4.30
589
586
Total (95% CI)
Total events: 4 (Dextran), 11 (LDUH)
Test for heterogeneity: Chi² = 3.31, df = 3 (P = 0.35), I² = 9.4%
Test for overall effect: Z = 1.65 (P = 0.10)
0.01
2
3
4
100.00
0.1
1
10
Favours Dextran
5
Dextran vs aspirin
6
Figure 110. Dextran vs aspirin – DVT
RR (fixed)
95% CI
Not estimable
Not estimable
0.13 [0.02, 1.04]
Not estimable
0.33 [0.01, 7.98]
Not estimable
0.94 [0.14, 6.48]
2.88 [0.12, 69.80]
0.41 [0.15, 1.18]
100
Favours LDUH
Review:
VTE Oral anticoagulants and Dextrans
Comparison:34 Dextran vs aspirin
Outcome: 01 DVT
Study
or sub-category
Dex
n/N
HARRIS1974
14/62
Aspirin
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
18/51
100.00
0.64 [0.35, 1.16]
51
100.00
0.64 [0.35, 1.16]
62
Total (95% CI)
Total events: 14 (Dex), 18 (Aspirin)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.48 (P = 0.14)
0.01
7
8
Weight
%
0.1
1
Favours Dextran
10
100
Favours aspirin
Figure 111. Dextran vs aspirin – proximal DVT
Review:
VTE Oral anticoagulants and Dextrans
Comparison:34 Dextran vs aspirin
Outcome: 02 Proximal DVT
Study
or sub-category
HARRIS1974
Dex
n/N
8/62
62
Total (95% CI)
Total events: 8 (Dex), 10 (Aspirin)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.96 (P = 0.34)
Aspirin
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
10/51
100.00
0.66 [0.28, 1.54]
51
100.00
0.66 [0.28, 1.54]
0.01
9
10
11
Weight
%
0.1
Favours Dextran
1
10
100
Favours aspirin
12
13
14
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
581 of 648
DRAFT FOR CONSULTATION
1
UFH vs no prophylaxis
2
Figure 112. UFH vs no prophylaxis – DVT
Review:
VTE Heparins
Comparison: 01 UFH vs no prophylaxis
Outcome: 01 DVT
Study
or sub-category
UFH
n/N
ABERNETHY1974
ABRAHAM1975
ANON1975
ANON1979
BALLARD1973
BEISAW1988
BELCH1980
BERGQVIST1979 i
BERGQVIST1979 ii
BERGQVIST1980
CALOGHERA1984
CERRATO1978
CHRISTENSEN1989A
CLARKEPEARSON 1990
CLARKEPEARSON1983
COE1978
COVEY1975
DECHAVANNE1974
DECHAVANNE1975
GALLUS1973 i
GALLUS1973 ii
GALLUS1973 iii
GALLUS1976A
GORDONSMITH1972
HAMPSON1974A
HEDLUND1981
KAKKAR1972
KETTUNEN1974
KOPPENHAGEN1982
KRAYTMAN1977 i
KRAYTMAN1977 ii
KUTNOWSKI1977
LAHNBORG1975
LAHNBORG1980
LAWRENCE1977
LOEW1977
LOWE1981
MACINTYRE1974
MANNUCCI1976
MORRIS1974
MORRIS1977
MOSKOVITZ1978 i
MOSKOVITZ1978 ii
NICOLAIDES1972
PLANTE1979
RIBAUDO1975
ROBERTS1975
SASAHARA1984 i
SASAHARA1984 ii
SEBESERI1975
SPEBAR1981
STRAND1975
SVENDHANSEN1981
TABERNER1978
TORNGREN1979 i
VANDENDRIS1980
VANGELOVEN1977
WELINBERGER1982
WU1977
XABREGAS1978
ZIEMSKI1979
4/63
1/12
2/34
30/323
2/55
16/65
3/24
24/50
18/28
6/46
2/40
3/50
3/28
9/104
9/97
6/28
4/53
2/29
1/20
1/100
1/8
3/23
9/408
17/100
15/48
2/29
3/39
7/83
32/162
3/25
6/23
1/6
3/58
15/70
8/122
5/57
7/51
15/128
3/23
3/27
12/24
8/35
10/29
1/122
3/42
7/22
10/39
32/190
17/181
4/34
3/24
3/50
15/65
3/49
10/63
3/31
13/74
8/17
0/44
0/25
0/30
Nil
n/N
RR (random)
95% CI
Weight
%
3/62
5/13
11/30
54/323
16/55
34/65
8/25
32/51
20/22
14/51
3/40
17/50
3/27
19/103
12/88
5/24
5/52
13/29
8/21
16/109
3/9
11/23
49/412
21/50
25/52
11/28
17/39
48/117
15/50
11/22
17/27
4/13
11/54
28/69
20/120
19/63
16/49
47/128
10/24
16/32
16/24
19/32
8/33
29/122
14/66
10/19
8/45
22/90
18/93
18/31
2/19
10/50
28/65
11/48
20/61
13/33
20/80
5/18
6/44
12/25
8/20
0.92
0.55
0.95
3.03
0.96
2.83
1.22
3.21
3.35
1.80
0.70
1.27
0.87
2.10
1.93
1.44
1.14
0.98
0.56
0.55
0.53
1.31
2.22
2.66
2.77
0.96
1.30
2.10
2.71
1.30
2.09
0.57
1.19
2.69
2.01
1.70
1.97
2.70
1.28
1.33
2.81
2.29
2.00
0.56
1.24
2.09
1.90
2.84
2.45
1.60
0.73
1.18
2.71
1.20
2.29
1.28
2.42
1.74
0.29
0.31
0.30
3929
3639
Total (95% CI)
Total events: 466 (UFH), 994 (Nil)
Test for heterogeneity: Chi² = 129.15, df = 60 (P < 0.00001), I² = 53.5%
Test for overall effect: Z = 9.98 (P < 0.00001)
0.01
3
4
100.00
0.1
Favours UFH
1
10
RR (random)
95% CI
1.31
0.22
0.16
0.56
0.13
0.47
0.39
0.77
0.71
0.48
0.67
0.18
0.96
0.47
0.68
1.03
0.78
0.15
0.13
0.07
0.38
0.27
0.19
0.40
0.65
0.18
0.18
0.21
0.66
0.24
0.41
0.54
0.25
0.53
0.39
0.29
0.42
0.32
0.31
0.22
0.75
0.38
1.42
0.03
0.34
0.60
1.44
0.69
0.49
0.20
1.19
0.30
0.54
0.27
0.48
0.25
0.70
1.69
0.08
0.04
0.04
[0.31,
[0.03,
[0.04,
[0.37,
[0.03,
[0.29,
[0.12,
[0.53,
[0.52,
[0.20,
[0.12,
[0.06,
[0.21,
[0.22,
[0.30,
[0.36,
[0.22,
[0.04,
[0.02,
[0.01,
[0.05,
[0.09,
[0.09,
[0.24,
[0.39,
[0.04,
[0.06,
[0.10,
[0.39,
[0.08,
[0.20,
[0.08,
[0.07,
[0.31,
[0.18,
[0.12,
[0.19,
[0.19,
[0.10,
[0.07,
[0.46,
[0.20,
[0.65,
[0.00,
[0.10,
[0.29,
[0.63,
[0.43,
[0.26,
[0.08,
[0.22,
[0.09,
[0.32,
[0.08,
[0.25,
[0.08,
[0.38,
[0.69,
[0.00,
[0.00,
[0.00,
5.62]
1.60]
0.67]
0.84]
0.52]
0.76]
1.30]
1.09]
0.96]
1.13]
3.78]
0.56]
4.37]
0.99]
1.54]
2.95]
2.76]
0.62]
0.96]
0.50]
2.92]
0.85]
0.37]
0.70]
1.08]
0.72]
0.55]
0.43]
1.11]
0.75]
0.87]
3.87]
0.86]
0.90]
0.86]
0.73]
0.93]
0.54]
1.00]
0.68]
1.22]
0.75]
3.12]
0.25]
1.10]
1.27]
3.29]
1.12]
0.90]
0.53]
6.40]
1.03]
0.91]
0.90]
0.95]
0.78]
1.31]
4.16]
1.33]
0.64]
0.65]
0.44 [0.38, 0.52]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
582 of 648
DRAFT FOR CONSULTATION
1
Figure 113. UFH vs no prophylaxis – pulmonary embolism
Review:
VTE Heparins
Comparison:01 UFH vs no prophylaxis
Outcome: 02 Pulmonary embolism
Study
or sub-category
UFH
n/N
ABERNETHY1974
ANON1979
BEIJANI1983
BERGQVIST1979 i
CLARKEPEARSON1983
COE1978
GALASKO1976
KIIL1979
LAHNBORG1975
LAHNBORG1976
LOEW1977
LOWE1981
MORRIS1974
MORRIS1977
MOSKOVITZ1978 i
MOSKOVITZ1978 ii
RIBAUDO1975
SPEBAR1981
VANDENDRIS1980
VANGELOVEN1977
WELINBERGER1982
WILLIAMS1978
0/21
12/323
0/17
18/72
4/97
1/28
1/50
0/650
9/58
0/24
0/57
2/51
0/27
0/24
3/35
2/29
0/22
1/24
0/31
2/74
0/20
19/106
Nil
n/N
RR (fixed)
95% CI
5/26
15/323
1/17
14/71
0/88
1/24
2/50
6/663
24/54
0/24
0/63
5/49
1/32
0/24
1/19
1/33
1/19
0/19
0/33
9/80
0/20
18/106
4.58
13.90
1.39
13.06
0.49
1.00
1.85
5.96
23.03
1840
1837
Total (95% CI)
Total events: 74 (UFH), 104 (Nil)
Test for heterogeneity: Chi² = 21.63, df = 16 (P = 0.16), I² = 26.0%
Test for overall effect: Z = 2.52 (P = 0.01)
100.00
4.72
1.28
1.20
0.87
1.49
0.51
8.01
16.67
0.01
2
3
Weight
%
0.1
Favours UFH
1
10
RR (fixed)
95% CI
0.11 [0.01, 1.91]
0.80 [0.38, 1.68]
0.33 [0.01, 7.65]
1.27 [0.68, 2.35]
8.17 [0.45, 149.68]
0.86 [0.06, 12.98]
0.50 [0.05, 5.34]
0.08 [0.00, 1.39]
0.35 [0.18, 0.68]
Not estimable
Not estimable
0.38 [0.08, 1.89]
0.39 [0.02, 9.27]
Not estimable
1.63 [0.18, 14.60]
2.28 [0.22, 23.82]
0.29 [0.01, 6.72]
2.40 [0.10, 55.79]
Not estimable
0.24 [0.05, 1.08]
Not estimable
1.06 [0.59, 1.90]
0.70 [0.53, 0.93]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
583 of 648
DRAFT FOR CONSULTATION
1
Figure 114. UFH vs no prophylaxis – proximal DVT
Review:
VTE Heparins
Comparison:01 UFH vs no prophylaxis
Outcome: 03 Proximal DVT
Study
or sub-category
UFH
n/N
ANON1975
ANON1979
BEISAW1988
BELCH1980
BERGQVIST1979 i
BERGQVIST1979 ii
BERGQVIST1980
CLARKEPEARSON1983
GALLUS1973 iii
GALLUS1976A
HEDLUND1981
KILLEWICH2002
LOEW1977
MORRIS1974
MOSKOVITZ1978 i
MOSKOVITZ1978 ii
NICOLAIDES1972
RIBAUDO1975
SPEBAR1981
TABERNER1978
VANDENDRIS1980
VINAZZER1980
WELINBERGER1982
XABREGAS1978
0/34
5/85
3/63
0/24
10/50
10/28
3/46
5/97
2/23
4/408
1/29
0/15
0/57
0/27
4/35
4/29
0/122
0/22
1/24
1/31
1/31
1/350
3/17
0/25
Nil
n/N
RR (fixed)
95% CI
3/30
3/83
12/65
1/25
14/51
11/22
9/51
1/88
2/23
12/412
2/28
0/15
3/63
5/32
9/32
5/22
9/122
2/19
0/19
2/33
2/33
14/365
2/18
5/25
2.79
2.28
8.88
1.11
10.42
9.26
6.42
0.79
1.50
8.98
1.53
1672
1676
Total (95% CI)
Total events: 58 (UFH), 128 (Nil)
Test for heterogeneity: Chi² = 25.95, df = 22 (P = 0.25), I² = 15.2%
Test for overall effect: Z = 5.45 (P < 0.00001)
100.00
2.50
3.80
7.07
4.28
7.14
2.01
0.42
1.46
1.46
10.31
1.46
4.14
0.01
2
3
Weight
%
0.1
Favours UFH
1
10
RR (fixed)
95% CI
0.13 [0.01, 2.35]
1.63 [0.40, 6.59]
0.26 [0.08, 0.87]
0.35 [0.01, 8.12]
0.73 [0.36, 1.48]
0.71 [0.37, 1.37]
0.37 [0.11, 1.28]
4.54 [0.54, 38.08]
1.00 [0.15, 6.51]
0.34 [0.11, 1.04]
0.48 [0.05, 5.03]
Not estimable
0.16 [0.01, 2.99]
0.11 [0.01, 1.85]
0.41 [0.14, 1.19]
0.61 [0.18, 2.00]
0.05 [0.00, 0.89]
0.17 [0.01, 3.41]
2.40 [0.10, 55.79]
0.53 [0.05, 5.58]
0.53 [0.05, 5.58]
0.07 [0.01, 0.56]
1.59 [0.30, 8.37]
0.09 [0.01, 1.56]
0.45 [0.34, 0.60]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
584 of 648
DRAFT FOR CONSULTATION
1
Figure 115. UFH vs no prophylaxis – major bleed
Review:
VTE Heparins
Comparison: 01 UFH vs no prophylaxis
Outcome: 04 Bleeding
Study
or sub-category
UFH
n/N
ABERNETHY1974
ABRAHAM1975
ABRAHAM1979
ALLEN1978
ANON1975
ANON1979
BEIJANI1983
BEISAW1988
BELCH1980
BERGQVIST1979 i
BERGQVIST1979 ii
BERGQVIST1980
CALOGHERA1984
CERRATO1978
CLARKEPEARSON1983
COVEY1975
DECHAVANNE1974
DECHAVANNE1975
GALASKO1976
GORDONSMITH1972
HAMPSON1974A
HEDLUND1981
JOURDAN1984
KAKKAR1972
KETTUNEN1974
KIIL1979
KRAYTMAN1976
KRAYTMAN1977 i
KRAYTMAN1977 ii
KRUSEBLINKENBER1980
KUTNOWSKI1977
LAHNBORG1975
LAWRENCE1977
LOEW1977
LOWE1981
MACINTYRE1974
MANNUCCI1976
MARCHETTI1983
MORRIS1974
MORRIS1977
MOSKOVITZ1978 i
MOSKOVITZ1978 ii
NICOLAIDES1972
RIBAUDO1975
ROBERTS1975
SAGAR1975
SASAHARA1984 i
SASAHARA1984 ii
SEBESERI1975
SPEBAR1981
TABERNER1978
TORNGREN1979 i
VANDENDRIS1980
VANGELOVEN1977
VINAZZER1980
WELINBERGER1982
WU1977
XABREGAS1978
ZIEMSKI1979
0/63
0/12
2/20
6/30
1/34
11/323
1/17
4/74
8/24
0/72
0/28
2/53
0/40
2/50
8/97
14/53
3/29
0/20
0/50
2/105
0/48
1/30
0/21
0/39
2/83
0/650
0/21
0/25
1/23
11/29
0/6
0/58
4/133
0/57
2/51
1/128
4/23
0/30
1/27
0/24
0/29
3/35
1/128
2/75
0/39
4/264
7/222
4/214
2/34
0/24
5/49
24/66
3/31
1/74
11/402
1/20
8/44
4/27
1/30
Control
n/N
RR (fixed)
95% CI
Weight
%
0/62
0/13
2/20
0/30
0/30
2/323
1/17
0/74
1/25
0/71
0/22
0/58
0/40
1/50
6/88
10/52
2/29
1/21
1/50
0/51
0/52
1/29
0/21
0/39
0/117
0/663
1/28
0/22
1/27
6/33
0/13
0/54
4/129
0/63
2/49
2/128
2/24
0/30
2/32
0/24
0/33
0/32
0/122
2/75
0/45
0/236
2/108
2/110
0/31
0/19
0/48
23/62
13/33
1/80
3/404
2/20
9/44
5/26
0/20
1.68
0.42
0.45
1.68
0.84
0.42
0.82
0.40
0.84
5.29
8.48
1.68
1.23
1.26
0.56
0.85
0.35
1.09
0.77
4.72
3.41
1.71
1.68
1.64
1.54
0.44
0.43
1.68
0.44
2.26
2.22
0.44
0.42
19.93
10.58
0.81
2.51
1.68
7.56
4.28
0.50
4507
4251
Total (95% CI)
Total events: 172 (UFH), 110 (Control)
Test for heterogeneity: Chi² = 39.94, df = 40 (P = 0.47), I² = 0%
Test for overall effect: Z = 3.45 (P = 0.0006)
100.00
0.01
2
3
0.1
Favours UFH
1
10
RR (fixed)
95% CI
Not estimable
Not estimable
1.00 [0.16, 6.42]
13.00 [0.76, 220.96]
2.66 [0.11, 62.87]
5.50 [1.23, 24.62]
1.00 [0.07, 14.72]
9.00 [0.49, 164.25]
8.33 [1.13, 61.70]
Not estimable
Not estimable
5.46 [0.27, 111.26]
Not estimable
2.00 [0.19, 21.36]
1.21 [0.44, 3.35]
1.37 [0.67, 2.81]
1.50 [0.27, 8.32]
0.35 [0.02, 8.10]
0.33 [0.01, 7.99]
2.45 [0.12, 50.17]
Not estimable
0.97 [0.06, 14.74]
Not estimable
Not estimable
7.02 [0.34, 144.42]
Not estimable
0.44 [0.02, 10.28]
Not estimable
1.17 [0.08, 17.74]
2.09 [0.88, 4.93]
Not estimable
Not estimable
0.97 [0.25, 3.80]
Not estimable
0.96 [0.14, 6.56]
0.50 [0.05, 5.45]
2.09 [0.42, 10.32]
Not estimable
0.59 [0.06, 6.18]
Not estimable
Not estimable
6.42 [0.34, 119.61]
2.86 [0.12, 69.55]
1.00 [0.14, 6.91]
Not estimable
8.05 [0.44, 148.72]
1.70 [0.36, 8.06]
1.03 [0.19, 5.53]
4.57 [0.23, 91.66]
Not estimable
10.78 [0.61, 189.77]
0.98 [0.62, 1.54]
0.25 [0.08, 0.78]
1.08 [0.07, 16.97]
3.68 [1.04, 13.11]
0.50 [0.05, 5.08]
0.89 [0.38, 2.09]
0.77 [0.23, 2.56]
2.03 [0.09, 47.53]
1.46 [1.18, 1.82]
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
585 of 648
DRAFT FOR CONSULTATION
1
LMWH vs no prophylaxis
2
Figure 116. LMWH vs no prophylaxis – DVT
Review:
VTE Heparins
Comparison:02 LMWH vs no prophylaxis
Outcome: 01 DVT
Study
or sub-category
AGNELLI1998
BERGQVIST1996B
BERGQVIST1996F
DICKINSON1998
JORGENSEN1992
KALODIKI1996
LASSEN1988
LASSEN1989
LASSEN1991
LECLERC1992
LEGAGNEUX1987
LEVINE1996
MARASSI1993
MELON1987
MICHOT2002A
NURMOHAMED1996
OCKELFORD1989
SAMAMA1997
SOURMELIS1995
TORHOLM1991
TURPIE1986
VALLE1988
WARWICK1995A
WIRTH2001A
YOO1997
LMWH
n/N
Nil
n/N
22/130
21/117
3/39
4/23
9/30
3/13
35/107
14/53
29/93
11/65
0/44
28/96
2/30
10/64
1/66
31/166
4/95
11/78
24/72
9/58
3/30
0/50
22/78
1/117
1/50
RR (fixed)
95% CI
RR (fixed)
95% CI
43/130
43/116
9/41
3/22
22/38
13/14
53/97
23/54
44/97
37/64
0/45
60/103
11/31
14/58
10/64
47/179
14/88
28/75
56/78
19/54
20/33
3/50
33/78
5/122
8/50
7.02
7.05
1.43
0.50
3.17
2.04
9.08
3.72
7.03
6.09
9.45
1.77
2.40
1.66
7.38
2.37
4.66
8.78
3.21
3.11
0.57
5.39
0.80
1.31
0.51 [0.33, 0.80]
0.48 [0.31, 0.76]
0.35 [0.10, 1.20]
1.28 [0.32, 5.06]
0.52 [0.28, 0.95]
0.25 [0.09, 0.68]
0.60 [0.43, 0.83]
0.62 [0.36, 1.07]
0.69 [0.47, 1.00]
0.29 [0.16, 0.52]
Not estimable
0.50 [0.35, 0.71]
0.19 [0.05, 0.78]
0.65 [0.31, 1.34]
0.10 [0.01, 0.74]
0.71 [0.48, 1.06]
0.26 [0.09, 0.77]
0.38 [0.20, 0.70]
0.46 [0.33, 0.66]
0.44 [0.22, 0.89]
0.17 [0.05, 0.50]
0.14 [0.01, 2.70]
0.67 [0.43, 1.03]
0.21 [0.02, 1.76]
0.13 [0.02, 0.96]
1764
1781
Total (95% CI)
Total events: 298 (LMWH), 618 (Nil)
Test for heterogeneity: Chi² = 31.11, df = 23 (P = 0.12), I² = 26.1%
Test for overall effect: Z = 12.01 (P < 0.00001)
100.00
0.49 [0.44, 0.55]
0.01
3
4
Weight
%
0.1
1
Favours LMWH
10
100
Favours nil
Figure 117. LMWH vs no prophylaxis – pulmonary embolism
Review:
VTE Heparins
Comparison:02 LMWH vs no prophylaxis
Outcome: 02 Pulmonary embolism
Study
or sub-category
AGNELLI1998
BERGQVIST1996B
DICKINSON1998
HO1999
KALODIKI1996
LEVINE1996
MICHOT2002A
NURMOHAMED1996
OCKELFORD1989
PEZZULI1989
SAMAMA1997
TORHOLM1991
VALLE1988
YOO1997
LMWH
n/N
0/130
0/117
0/23
0/134
3/29
1/122
1/66
1/241
0/95
2/2247
0/85
0/58
0/50
1/50
Nil
n/N
RR (fixed)
95% CI
Weight
%
4.64
7.77
1/130
2/116
0/22
3/169
5/12
0/124
0/64
2/244
2/88
8/2251
0/85
1/54
0/50
3/50
9.59
21.89
1.53
1.57
6.15
8.03
24.74
4.80
9.28
3447
3459
Total (95% CI)
Total events: 9 (LMWH), 27 (Nil)
Test for heterogeneity: Chi² = 4.53, df = 10 (P = 0.92), I² = 0%
Test for overall effect: Z = 3.19 (P = 0.001)
0.01
5
100.00
0.1
Favours LMWH
1
10
RR (fixed)
95% CI
0.33 [0.01, 8.11]
0.20 [0.01, 4.09]
Not estimable
0.18 [0.01, 3.45]
0.25 [0.07, 0.88]
3.05 [0.13, 74.12]
2.91 [0.12, 70.15]
0.51 [0.05, 5.55]
0.19 [0.01, 3.81]
0.25 [0.05, 1.18]
Not estimable
0.31 [0.01, 7.47]
Not estimable
0.33 [0.04, 3.10]
0.35 [0.18, 0.67]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
586 of 648
DRAFT FOR CONSULTATION
1
Figure 118. LMWH vs no prophylaxis – proximal DVT
Review:
VTE Heparins
Comparison:02 LMWH vs no prophylaxis
Outcome: 03 Proximal DVT
Study
or sub-category
AGNELLI1998
KALODIKI1996
LASSEN1988
LASSEN1991
LECLERC1992
LEVINE1996
NURMOHAMED1996
SAMAMA1997
SOURMELIS1995
TORHOLM1991
TURPIE1986
VALLE1988
WARWICK1995A
YOO1997
LMWH
n/N
Nil
n/N
RR (random)
95% CI
17/129
9/14
28/97
35/97
12/64
16/103
21/179
12/75
19/78
5/54
10/50
2/50
14/78
3/50
9.77
11.36
12.97
15.33
1.65
5.03
11.87
4.93
5.15
1.58
4.91
1.45
11.51
2.49
1125
1118
Total (95% CI)
Total events: 85 (LMWH), 203 (Nil)
Test for heterogeneity: Chi² = 24.24, df = 13 (P = 0.03), I² = 46.4%
Test for overall effect: Z = 4.99 (P < 0.00001)
100.00
7/130
8/32
13/107
24/93
0/65
2/96
12/166
2/78
2/72
0/58
2/50
0/50
12/78
1/50
0.01
2
3
4
Weight
%
0.1
1
Favours LMWH
10
RR (random)
95% CI
0.41
0.39
0.42
0.72
0.04
0.13
0.62
0.16
0.11
0.08
0.20
0.20
0.86
0.33
[0.18,
[0.19,
[0.23,
[0.46,
[0.00,
[0.03,
[0.31,
[0.04,
[0.03,
[0.00,
[0.05,
[0.01,
[0.42,
[0.04,
0.95]
0.80]
0.77]
1.10]
0.65]
0.57]
1.21]
0.69]
0.47]
1.50]
0.87]
4.06]
1.73]
3.10]
0.38 [0.26, 0.56]
100
Favours nil
Figure 119. LMWH vs no prophylaxis – major bleed
Review:
VTE Heparins
Comparison:02 LMWH vs no prophylaxis
Outcome: 04 Major bleed
Study
or sub-category
AGNELLI1998
BALAS1992
BERGQVIST1996F
DICKINSON1998
HO1999
JORGENSEN1992
LASSEN1988
LASSEN1989
LECLERC1992
LEGAGNEUX1987
LEVINE1996
MELON1987
MICHOT2002A
NURMOHAMED1996
OCKELFORD1989
PEZZULI1989
SAMAMA1997
TURPIE1986
VALLE1988
WIRTH2001A
Treatment
n/N
4/153
0/94
1/39
3/23
3/134
0/41
1/118
1/68
0/66
0/44
3/122
0/67
0/66
6/241
4/102
67/2247
1/85
1/50
0/50
0/117
Control
n/N
RR (fixed)
95% CI
Weight
%
4/154
2/95
0/41
0/22
1/169
0/41
2/116
1/74
1/65
0/45
3/124
0/63
0/64
2/244
4/95
30/2251
1/85
2/50
0/50
0/122
7.26
4.53
0.89
0.93
1.61
3.67
1.74
2.75
5.42
3.62
7.54
54.57
1.82
3.64
3927
3970
Total (95% CI)
Total events: 95 (Treatment), 53 (Control)
Test for heterogeneity: Chi² = 10.50, df = 13 (P = 0.65), I² = 0%
Test for overall effect: Z = 3.43 (P = 0.0006)
0.01
5
6
100.00
0.1
Favours LMWH
1
10
RR (fixed)
95% CI
1.01 [0.26, 3.95]
0.20 [0.01, 4.15]
3.15 [0.13, 75.08]
6.71 [0.37, 122.83]
3.78 [0.40, 35.96]
Not estimable
0.49 [0.05, 5.35]
1.09 [0.07, 17.06]
0.33 [0.01, 7.92]
Not estimable
1.02 [0.21, 4.94]
Not estimable
Not estimable
3.04 [0.62, 14.90]
0.93 [0.24, 3.62]
2.24 [1.46, 3.43]
1.00 [0.06, 15.73]
0.50 [0.05, 5.34]
Not estimable
Not estimable
1.77 [1.28, 2.46]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
587 of 648
DRAFT FOR CONSULTATION
1
LMWH preoperative vs postoperative initiation
2
Figure 120. LMWH preoperative vs postoperative initiation – DVT
Review:
VTE Heparins
Comparison:04 LMWH preoperative vs postoperative initiation
Outcome: 01 DVT
Study
or sub-category
PALARETTI1996
Pre-op initiation
n/N
Post-op initiation
n/N
27/65
RR (fixed)
95% CI
Weight
%
24/66
65
66
Total (95% CI)
Total events: 27 (Pre-op initiation), 24 (Post-op initiation)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.61 (P = 0.54)
0.01
3
0.1
1
Favours pre-op start
10
RR (fixed)
95% CI
100.00
1.14 [0.74, 1.76]
100.00
1.14 [0.74, 1.76]
100
Favours post-op
4
Figure 121. LMWH preoperative vs postoperative initiation – pulmonary
5
embolism
Review:
VTE Heparins
Comparison: 04 LMWH preoperative vs postoperative initiation
Outcome:
02 Pulmonary embolism
Study
or sub-category
PALARETTI1996
Pre-op initiation
n/N
Post-op initiation
n/N
0/90
0
Total (95% CI)
Total events: 0 (Pre-op initiation), 0 (Post-op initiation)
Test for heterogeneity: not applicable
Test for overall effect: not applicable
RR (fixed)
95% CI
RR (fixed)
95% CI
0/89
Not estimable
0
Not estimable
0.01
6
Weight
%
0.1
1
Favours pre-op start
10
100
Favours post-op
7
Figure 122. LMWH preoperative vs postoperative initiation – proximal
8
DVT
Review:
VTE Heparins
Comparison: 04 LMWH preoperative vs postoperative initiation
Outcome:
03 Proximal DVT
Study
or sub-category
PALARETTI1996
Pre-op initiation
n/N
Post-op initiation
n/N
7/65
65
Total (95% CI)
Total events: 7 (Pre-op initiation), 4 (Post-op initiation)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.96 (P = 0.34)
RR (fixed)
95% CI
RR (fixed)
95% CI
4/66
100.00
1.78 [0.55, 5.78]
66
100.00
1.78 [0.55, 5.78]
0.01
9
Weight
%
0.1
Favours pre-op start
1
10
100
Favours post-op
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
588 of 648
DRAFT FOR CONSULTATION
1
Figure 123. LMWH preoperative vs postoperative initiation – major bleed
Review:
VTE Heparins
Comparison: 04 LMWH preoperative vs postoperative initiation
Outcome:
04 Major bleed
Study
or sub-category
PALARETTI1996
Pre-op initiation
n/N
Post-op initiation
n/N
2/90
90
Total (95% CI)
Total events: 2 (Pre-op initiation), 3 (Post-op initiation)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.46 (P = 0.64)
RR (fixed)
95% CI
RR (fixed)
95% CI
3/89
100.00
0.66 [0.11, 3.85]
89
100.00
0.66 [0.11, 3.85]
0.01
2
3
4
Weight
%
0.1
1
Favours pre-op start
10
100
Favours post-op
5
6
LMWH vs no prophylaxis – subgrouped by preoperative or
postoperative initiation
7
Figure 124. LMWH vs no prophylaxis – subgrouped by preoperative or
8
postoperative initiation – DVT
Review:
VTE Heparins
Comparison: 05 LMWH vs no prophylaxis - subgrouped by preoperative or postoperative initiation
Outcome: 01 DVT
Study
or sub-category
LMWH
n/N
Nil
n/N
RR (fixed)
95% CI
Weight
%
01 Preoperative
21/117
43/116
BERGQVIST1996B
9/30
22/38
JORGENSEN1992
3/13
13/14
KALODIKI1996
35/107
53/97
LASSEN1988
14/53
23/54
LASSEN1989
29/93
44/97
LASSEN1991
0/44
0/45
LEGAGNEUX1987
2/30
11/31
MARASSI1993
1/66
10/64
MICHOT2002A
4/95
14/88
OCKELFORD1989
24/72
56/78
SOURMELIS1995
9/58
19/54
TORHOLM1991
0/50
3/50
VALLE1988
22/78
33/78
WARWICK1995A
1/50
8/50
YOO1997
956
954
Subtotal (95% CI)
Total events: 174 (LMWH), 352 (Nil)
Test for heterogeneity: Chi² = 16.56, df = 13 (P = 0.22), I² = 21.5%
Test for overall effect: Z = 9.11 (P < 0.00001)
7.09
3.19
2.05
9.12
3.74
7.07
02 Postoperative
22/130
43/130
AGNELLI1998
3/39
9/41
BERGQVIST1996F
11/65
37/64
LECLERC1992
28/96
60/103
LEVINE1996
10/64
14/58
MELON1987
31/166
47/179
NURMOHAMED1996
11/78
28/75
SAMAMA1997
3/30
20/33
TURPIE1986
1/117
5/122
WIRTH2001A
785
805
Subtotal (95% CI)
Total events: 120 (LMWH), 263 (Nil)
Test for heterogeneity: Chi² = 12.37, df = 8 (P = 0.14), I² = 35.3%
Test for overall effect: Z = 7.94 (P < 0.00001)
1741
1759
Total (95% CI)
Total events: 294 (LMWH), 615 (Nil)
Test for heterogeneity: Chi² = 29.49, df = 22 (P = 0.13), I² = 25.4%
Test for overall effect: Z = 12.09 (P < 0.00001)
0.01
9
1.78
1.67
2.39
8.82
3.23
0.57
5.42
1.31
57.44
0.48 [0.31, 0.76]
0.52 [0.28, 0.95]
0.25 [0.09, 0.68]
0.60 [0.43, 0.83]
0.62 [0.36, 1.07]
0.69 [0.47, 1.00]
Not estimable
0.19 [0.05, 0.78]
0.10 [0.01, 0.74]
0.26 [0.09, 0.77]
0.46 [0.33, 0.66]
0.44 [0.22, 0.89]
0.14 [0.01, 2.70]
0.67 [0.43, 1.03]
0.13 [0.02, 0.96]
0.50 [0.43, 0.58]
7.06
1.44
6.12
9.50
2.41
7.42
4.68
3.13
0.80
42.56
0.51
0.35
0.29
0.50
0.65
0.71
0.38
0.17
0.21
0.47
100.00
0.1
Favours LMWH
1
10
RR (fixed)
95% CI
[0.33,
[0.10,
[0.16,
[0.35,
[0.31,
[0.48,
[0.20,
[0.05,
[0.02,
[0.39,
0.80]
1.20]
0.52]
0.71]
1.34]
1.06]
0.70]
0.50]
1.76]
0.57]
0.49 [0.43, 0.55]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
589 of 648
DRAFT FOR CONSULTATION
1
2
3
Figure 125. LMWH vs no prophylaxis – subgrouped by preoperative or
4
postoperative initiation – pulmonary embolism
Review:
VTE Heparins
Comparison:05 LMWH vs no prophylaxis - subgrouped by preoperative or postoperative initiation
Outcome: 04 PE
Study
or sub-category
Treatment
n/N
Control
n/N
RR (fixed)
95% CI
Weight
%
01 Preoperative
0/117
2/116
BERGQVIST1996B
3/29
5/12
KALODIKI1996
1/66
0/64
MICHOT2002A
0/58
1/54
TORHOLM1991
1/50
3/50
YOO1997
320
296
Subtotal (95% CI)
Total events: 5 (Treatment), 11 (Control)
Test for heterogeneity: Chi² = 2.14, df = 4 (P = 0.71), I² = 0%
Test for overall effect: Z = 2.26 (P = 0.02)
02 Postoperative
0/85
SAMAMA1997
0
Subtotal (95% CI)
Total events: 0 (Treatment), 0 (Control)
Test for heterogeneity: not applicable
Test for overall effect: not applicable
17.14
48.30
3.47
10.60
20.49
100.00
0/85
0
100.00
0.01
0.20
0.25
2.91
0.31
0.33
0.36
[0.01,
[0.07,
[0.12,
[0.01,
[0.04,
[0.15,
4.09]
0.88]
70.15]
7.47]
3.10]
0.87]
Not estimable
Not estimable
405
381
Total (95% CI)
Total events: 5 (Treatment), 11 (Control)
Test for heterogeneity: Chi² = 2.14, df = 4 (P = 0.71), I² = 0%
Test for overall effect: Z = 2.26 (P = 0.02)
5
6
7
RR (fixed)
95% CI
0.1
Favours LMWH
1
10
0.36 [0.15, 0.87]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
590 of 648
DRAFT FOR CONSULTATION
1
Figure 126. LMWH vs no prophylaxis – subgrouped by preoperative or
2
postoperative initiation – proximal DVT
Review:
VTE Heparins
Comparison:05 LMWH vs no prophylaxis - subgrouped by preoperative or postoperative initiation
Outcome: 03 Proximal DVT
Study
or sub-category
Treatment
n/N
Control
n/N
RR (random)
95% CI
Weight
%
01 Preoperative
8/32
9/14
KALODIKI1996
13/107
28/97
LASSEN1988
24/93
35/97
LASSEN1991
2/72
19/78
SOURMELIS1995
0/58
5/54
TORHOLM1991
12/78
14/78
WARWICK1995A
1/50
3/50
YOO1997
490
468
Subtotal (95% CI)
Total events: 60 (Treatment), 113 (Control)
Test for heterogeneity: Chi² = 11.58, df = 6 (P = 0.07), I² = 48.2%
Test for overall effect: Z = 3.25 (P = 0.001)
02 Postoperative
7/130
17/129
AGNELLI1998
0/65
12/64
LECLERC1992
12/166
21/179
NURMOHAMED1996
361
372
Subtotal (95% CI)
Total events: 19 (Treatment), 50 (Control)
Test for heterogeneity: Chi² = 4.20, df = 2 (P = 0.12), I² = 52.3%
Test for overall effect: Z = 1.98 (P = 0.05)
851
840
Total (95% CI)
Total events: 79 (Treatment), 163 (Control)
Test for heterogeneity: Chi² = 16.02, df = 9 (P = 0.07), I² = 43.8%
Test for overall effect: Z = 4.01 (P < 0.0001)
0.01
3
4
13.56
15.96
19.76
5.51
1.60
13.78
2.55
72.70
0.39
0.42
0.72
0.11
0.08
0.86
0.33
0.47
[0.19,
[0.23,
[0.46,
[0.03,
[0.00,
[0.42,
[0.04,
[0.30,
0.80]
0.77]
1.10]
0.47]
1.50]
1.73]
3.10]
0.74]
11.33
1.67
14.31
27.30
0.41
0.04
0.62
0.41
[0.18,
[0.00,
[0.31,
[0.17,
0.95]
0.65]
1.21]
0.99]
100.00
0.1
Favours LMWH
1
10
RR (random)
95% CI
0.47 [0.32, 0.68]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
591 of 648
DRAFT FOR CONSULTATION
1
Figure 127. LMWH vs no prophylaxis – subgrouped by preoperative or
2
postoperative initiation – major bleed
Review:
VTE Heparins
Comparison:05 LMWH vs no prophylaxis - subgrouped by preoperative or postoperative initiation
Outcome: 02 Major bleed
Study
or sub-category
Treatment
n/N
Control
n/N
RR (fixed)
95% CI
Weight
%
01 Preoperative
0/94
2/95
BALAS1992
3/134
1/169
HO1999
0/41
0/41
JORGENSEN1992
1/118
2/116
LASSEN1988
1/68
1/74
LASSEN1989
0/44
0/45
LEGAGNEUX1987
0/66
0/64
MICHOT2002A
4/102
4/95
OCKELFORD1989
67/2247
30/2251
PEZZULI1989
0/50
0/50
VALLE1988
2964
3000
Subtotal (95% CI)
Total events: 76 (Treatment), 40 (Control)
Test for heterogeneity: Chi² = 5.48, df = 5 (P = 0.36), I² = 8.8%
Test for overall effect: Z = 3.34 (P = 0.0009)
4.75
1.69
3.85
1.83
7.90
57.19
77.20
02 Postoperative
4/153
4/154
AGNELLI1998
1/39
0/41
BERGQVIST1996F
0/66
1/65
LECLERC1992
3/122
3/124
LEVINE1996
0/67
0/63
MELON1987
6/241
2/244
NURMOHAMED1996
1/85
1/85
SAMAMA1997
0/117
0/122
WIRTH2001A
890
898
Subtotal (95% CI)
Total events: 15 (Treatment), 11 (Control)
Test for heterogeneity: Chi² = 2.38, df = 5 (P = 0.79), I² = 0%
Test for overall effect: Z = 0.79 (P = 0.43)
7.61
0.93
2.88
5.68
3.79
1.91
22.80
3854
3898
Total (95% CI)
Total events: 91 (Treatment), 51 (Control)
Test for heterogeneity: Chi² = 8.60, df = 11 (P = 0.66), I² = 0%
Test for overall effect: Z = 3.35 (P = 0.0008)
0.01
3
4
5
6
100.00
0.1
1
Favours LMWH
10
RR (fixed)
95% CI
0.20 [0.01, 4.15]
3.78 [0.40, 35.96]
Not estimable
0.49 [0.05, 5.35]
1.09 [0.07, 17.06]
Not estimable
Not estimable
0.93 [0.24, 3.62]
2.24 [1.46, 3.43]
Not estimable
1.90 [1.30, 2.77]
1.01 [0.26, 3.95]
3.15 [0.13, 75.08]
0.33 [0.01, 7.92]
1.02 [0.21, 4.94]
Not estimable
3.04 [0.62, 14.90]
1.00 [0.06, 15.73]
Not estimable
1.35 [0.64, 2.83]
1.77 [1.27, 2.48]
100
Favours nil
7
LMWH higher vs lower dose
8
Figure 128. LMWH higher vs lower dose - DVT
Review:
VTE Heparins
Comparison:06 LMWH higher vs lower dose
Outcome: 01 DVT
Study
or sub-category
ADOLF1999
BERGQVIST1995
COLWELL1994
HAUCH1988
SPIRO1994A
Higher dose
n/N
16/169
65/981
8/136
0/19
16/143
Lower dose
n/N
RR (random)
95% CI
Weight
%
21.02
36.86
17.85
1.81
22.46
17/172
124/976
28/136
2/16
21/149
1448
1449
Total (95% CI)
Total events: 105 (Higher dose), 192 (Lower dose)
Test for heterogeneity: Chi² = 7.88, df = 4 (P = 0.10), I² = 49.2%
Test for overall effect: Z = 2.68 (P = 0.007)
0.01
9
10
100.00
0.1
Favours higher dose
1
10
RR (random)
95% CI
0.96
0.52
0.29
0.17
0.79
[0.50,
[0.39,
[0.14,
[0.01,
[0.43,
1.83]
0.69]
0.60]
3.30]
1.46]
0.57 [0.38, 0.86]
100
Favours lower dose
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
592 of 648
DRAFT FOR CONSULTATION
1
Figure 129. LMWH higher vs lower dose – pulmonary embolism
Review:
VTE Heparins
Comparison:06 LMWH higher vs lower dose
Outcome: 02 Pulmonary embolism
Study
or sub-category
HAUCH1988
Higher dose
n/N
0/19
0
Total (95% CI)
Total events: 0 (Higher dose), 0 (Lower dose)
Test for heterogeneity: not applicable
Test for overall effect: not applicable
Lower dose
n/N
RR (fixed)
95% CI
3
RR (fixed)
95% CI
0/16
Not estimable
0
Not estimable
0.01
2
Weight
%
0.1
1
Favours higher dose
10
100
Favours lower dose
Figure 130. LMWH higher vs lower dose – proximal DVT
Review:
VTE Heparins
Comparison:06 LMWH higher vs lower dose
Outcome: 03 Proximal DVT
Study
or sub-category
ADOLF1999
COLWELL1994
SPIRO1994A
Higher dose
n/N
4/169
4/136
8/143
Lower dose
n/N
RR (fixed)
95% CI
Weight
%
0.01
4
5
6
10.55
42.56
46.89
2.04 [0.38, 10.97]
0.50 [0.15, 1.62]
0.93 [0.37, 2.33]
100.00
0.86 [0.45, 1.65]
2/172
8/136
9/149
448
457
Total (95% CI)
Total events: 16 (Higher dose), 19 (Lower dose)
Test for heterogeneity: Chi² = 1.85, df = 2 (P = 0.40), I² = 0%
Test for overall effect: Z = 0.45 (P = 0.65)
0.1
1
Favours higher dose
10
RR (fixed)
95% CI
100
Favours lower dose
Figure 131. LMWH higher vs lower dose – major bleed
Review:
VTE Heparins
Comparison:06 LMWH higher vs lower dose
Outcome: 04 Major bleed
Study
or sub-category
BERGQVIST1995
COLWELL1994
HAUCH1988
SPIRO1994A
Higher dose
n/N
13/1036
8/195
1/19
11/208
lower dose
n/N
RR (fixed)
95% CI
Weight
%
3/1034
3/203
0/16
7/199
22.02
21.56
3.96
52.46
1458
1452
Total (95% CI)
Total events: 33 (Higher dose), 13 (lower dose)
Test for heterogeneity: Chi² = 1.89, df = 3 (P = 0.60), I² = 0%
Test for overall effect: Z = 2.81 (P = 0.005)
0.01
7
8
9
100.00
0.1
Favours higher dose
1
10
RR (fixed)
95% CI
4.32
2.78
2.55
1.50
[1.24,
[0.75,
[0.11,
[0.59,
15.13]
10.31]
58.60]
3.80]
2.44 [1.31, 4.55]
100
Favours lower dose
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
593 of 648
DRAFT FOR CONSULTATION
1
LMWH vs no prophylaxis – subgrouped by dose
2
Figure 132. LMWH vs no prophylaxis – subgrouped by dose - DVT
Review:
VTE Heparins
Comparison: 07 LMWH vs no prophylaxis - subgrouped by dose
Outcome: 01 DVT
Study
or sub-category
LMWH
n/N
Nil
n/N
RR (fixed)
95% CI
Weight
%
01 'Low' dose
3/39
9/41
BERGQVIST1996F
35/107
53/97
LASSEN1988
14/53
23/54
LASSEN1989
29/93
44/97
LASSEN1991
0/44
0/45
LEGAGNEUX1987
2/30
11/31
MARASSI1993
10/64
14/58
MELON1987
1/66
10/64
MICHOT2002A
4/95
14/88
OCKELFORD1989
0/50
3/50
VALLE1988
1/117
5/122
WIRTH2001A
758
747
Subtotal (95% CI)
Total events: 99 (LMWH), 186 (Nil)
Test for heterogeneity: Chi² = 11.63, df = 9 (P = 0.24), I² = 22.6%
Test for overall effect: Z = 6.29 (P < 0.00001)
1.44
9.12
3.74
7.07
02 'Medium' dose
22/130
43/130
AGNELLI1998
21/117
43/116
BERGQVIST1996B
3/13
13/14
KALODIKI1996
11/78
28/75
SAMAMA1997
24/72
56/78
SOURMELIS1995
22/78
33/78
WARWICK1995A
1/50
8/50
YOO1997
538
541
Subtotal (95% CI)
Total events: 104 (LMWH), 224 (Nil)
Test for heterogeneity: Chi² = 6.21, df = 6 (P = 0.40), I² = 3.5%
Test for overall effect: Z = 7.57 (P < 0.00001)
03 'High' dose
9/30
22/38
JORGENSEN1992
11/65
37/64
LECLERC1992
28/96
60/103
LEVINE1996
31/166
47/179
NURMOHAMED1996
9/58
19/54
TORHOLM1991
3/30
20/33
TURPIE1986
445
471
Subtotal (95% CI)
Total events: 91 (LMWH), 205 (Nil)
Test for heterogeneity: Chi² = 10.31, df = 5 (P = 0.07), I² = 51.5%
Test for overall effect: Z = 7.05 (P < 0.00001)
1741
1759
Total (95% CI)
Total events: 294 (LMWH), 615 (Nil)
Test for heterogeneity: Chi² = 29.49, df = 22 (P = 0.13), I² = 25.4%
Test for overall effect: Z = 12.09 (P < 0.00001)
0.01
3
4
1.78
2.41
1.67
2.39
0.57
0.80
30.99
0.35 [0.10, 1.20]
0.60 [0.43, 0.83]
0.62 [0.36, 1.07]
0.69 [0.47, 1.00]
Not estimable
0.19 [0.05, 0.78]
0.65 [0.31, 1.34]
0.10 [0.01, 0.74]
0.26 [0.09, 0.77]
0.14 [0.01, 2.70]
0.21 [0.02, 1.76]
0.52 [0.42, 0.64]
7.06
7.09
2.05
4.68
8.82
5.42
1.31
36.43
0.51
0.48
0.25
0.38
0.46
0.67
0.13
0.47
[0.33,
[0.31,
[0.09,
[0.20,
[0.33,
[0.43,
[0.02,
[0.39,
0.80]
0.76]
0.68]
0.70]
0.66]
1.03]
0.96]
0.57]
3.19
6.12
9.50
7.42
3.23
3.13
32.58
0.52
0.29
0.50
0.71
0.44
0.17
0.47
[0.28,
[0.16,
[0.35,
[0.48,
[0.22,
[0.05,
[0.38,
0.95]
0.52]
0.71]
1.06]
0.89]
0.50]
0.58]
100.00
0.1
Favours LMWH
1
10
RR (fixed)
95% CI
0.49 [0.43, 0.55]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
594 of 648
DRAFT FOR CONSULTATION
1
Figure 133. LMWH vs no prophylaxis – subgrouped by dose –
2
pulmonary embolism
Review:
VTE Heparins
Comparison: 07 LMWH vs no prophylaxis - subgrouped by dose
Outcome:
02 Pulmonary embolism
Study
or sub-category
LMWH
n/N
Nil
n/N
RR (fixed)
95% CI
Weight
%
01 'Low' dose
1/66
0/64
MICHOT2002A
0/95
2/88
OCKELFORD1989
2/2247
8/2251
PEZZULI1989
0/50
0/50
VALLE1988
2458
2453
Subtotal (95% CI)
Total events: 3 (LMWH), 10 (Nil)
Test for heterogeneity: Chi² = 2.05, df = 2 (P = 0.36), I² = 2.5%
Test for overall effect: Z = 1.77 (P = 0.08)
1.57
8.03
24.74
34.34
02 'Medium' dose
0/130
1/130
AGNELLI1998
0/117
2/116
BERGQVIST1996B
0/134
3/169
HO1999
3/29
5/12
KALODIKI1996
0/85
0/85
SAMAMA1997
1/50
3/50
YOO1997
545
562
Subtotal (95% CI)
Total events: 4 (LMWH), 14 (Nil)
Test for heterogeneity: Chi² = 0.17, df = 4 (P = 1.00), I² = 0%
Test for overall effect: Z = 2.81 (P = 0.005)
4.64
7.77
9.59
21.89
03 'High' dose
1/122
0/124
LEVINE1996
1/241
2/244
NURMOHAMED1996
0/58
1/54
TORHOLM1991
421
422
Subtotal (95% CI)
Total events: 2 (LMWH), 3 (Nil)
Test for heterogeneity: Chi² = 1.14, df = 2 (P = 0.57), I² = 0%
Test for overall effect: Z = 0.39 (P = 0.70)
3424
3437
Total (95% CI)
Total events: 9 (LMWH), 27 (Nil)
Test for heterogeneity: Chi² = 4.53, df = 10 (P = 0.92), I² = 0%
Test for overall effect: Z = 3.19 (P = 0.001)
3
0.1
Favours LMWH
1
10
2.91 [0.12, 70.15]
0.19 [0.01, 3.81]
0.25 [0.05, 1.18]
Not estimable
0.36 [0.11, 1.12]
9.28
53.17
0.33 [0.01, 8.11]
0.20 [0.01, 4.09]
0.18 [0.01, 3.45]
0.25 [0.07, 0.88]
Not estimable
0.33 [0.04, 3.10]
0.25 [0.10, 0.66]
1.53
6.15
4.80
12.49
3.05
0.51
0.31
0.74
100.00
0.01
RR (fixed)
95% CI
[0.13,
[0.05,
[0.01,
[0.17,
74.12]
5.55]
7.47]
3.28]
0.35 [0.18, 0.67]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
595 of 648
DRAFT FOR CONSULTATION
1
Figure 134. LMWH vs no prophylaxis – subgrouped by dose – proximal
2
DVT
Review:
VTE Heparins
Comparison:07 LMWH vs no prophylaxis - subgrouped by dose
Outcome: 03 Proximal DVT
Study
or sub-category
LMWH
n/N
Nil
n/N
RR (random)
95% CI
Weight
%
01 'Low' dose
13/107
28/97
LASSEN1988
24/93
35/97
LASSEN1991
0/50
2/50
VALLE1988
250
244
Subtotal (95% CI)
Total events: 37 (LMWH), 65 (Nil)
Test for heterogeneity: Chi² = 2.52, df = 2 (P = 0.28), I² = 20.6%
Test for overall effect: Z = 2.54 (P = 0.01)
02 'Medium' dose
7/130
17/129
AGNELLI1998
8/32
9/14
KALODIKI1996
2/78
12/75
SAMAMA1997
2/72
19/78
SOURMELIS1995
12/78
14/78
WARWICK1995A
1/50
3/50
YOO1997
440
424
Subtotal (95% CI)
Total events: 32 (LMWH), 74 (Nil)
Test for heterogeneity: Chi² = 9.35, df = 5 (P = 0.10), I² = 46.5%
Test for overall effect: Z = 3.32 (P = 0.0009)
03 'High' dose
0/65
12/64
LECLERC1992
2/96
16/103
LEVINE1996
12/166
21/179
NURMOHAMED1996
0/58
5/54
TORHOLM1991
2/50
10/50
TURPIE1986
435
450
Subtotal (95% CI)
Total events: 16 (LMWH), 64 (Nil)
Test for heterogeneity: Chi² = 9.10, df = 4 (P = 0.06), I² = 56.1%
Test for overall effect: Z = 2.92 (P = 0.004)
1125
1118
Total (95% CI)
Total events: 85 (LMWH), 203 (Nil)
Test for heterogeneity: Chi² = 24.24, df = 13 (P = 0.03), I² = 46.4%
Test for overall effect: Z = 4.99 (P < 0.00001)
0.01
3
12.97
15.33
1.45
29.75
0.42
0.72
0.20
0.57
[0.23,
[0.46,
[0.01,
[0.37,
0.77]
1.10]
4.06]
0.88]
9.77
11.36
4.93
5.15
11.51
2.49
45.20
0.41
0.39
0.16
0.11
0.86
0.33
0.37
[0.18,
[0.19,
[0.04,
[0.03,
[0.42,
[0.04,
[0.21,
0.95]
0.80]
0.69]
0.47]
1.73]
3.10]
0.67]
1.65
5.03
11.87
1.58
4.91
25.04
0.04
0.13
0.62
0.08
0.20
0.21
[0.00,
[0.03,
[0.31,
[0.00,
[0.05,
[0.07,
0.65]
0.57]
1.21]
1.50]
0.87]
0.60]
100.00
0.1
Favours LMWH
1
10
RR (random)
95% CI
0.38 [0.26, 0.56]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
596 of 648
DRAFT FOR CONSULTATION
1
Figure 135. LMWH vs no prophylaxis – subgrouped by dose – major
2
bleed
Review:
VTE Heparins
Comparison:07 LMWH vs no prophylaxis - subgrouped by dose
Outcome: 04 Major bleed
Study
or sub-category
Treatment
n/N
Control
n/N
RR (fixed)
95% CI
Weight
%
01 'Low' dose
0/94
2/95
BALAS1992
1/39
0/41
BERGQVIST1996F
1/118
2/116
LASSEN1988
1/68
1/74
LASSEN1989
0/44
0/45
LEGAGNEUX1987
0/67
0/63
MELON1987
0/66
0/64
MICHOT2002A
4/102
4/95
OCKELFORD1989
67/2247
30/2251
PEZZULI1989
0/50
0/50
VALLE1988
0/117
0/122
WIRTH2001A
3012
3016
Subtotal (95% CI)
Total events: 74 (Treatment), 39 (Control)
Test for heterogeneity: Chi² = 5.23, df = 5 (P = 0.39), I² = 4.4%
Test for overall effect: Z = 3.24 (P = 0.001)
4.57
0.90
3.71
1.76
03 'High' dose
0/41
0/41
JORGENSEN1992
0/66
1/65
LECLERC1992
3/122
3/124
LEVINE1996
6/241
2/244
NURMOHAMED1996
1/50
2/50
TURPIE1986
520
524
Subtotal (95% CI)
Total events: 10 (Treatment), 8 (Control)
Test for heterogeneity: Chi² = 2.52, df = 3 (P = 0.47), I² = 0%
Test for overall effect: Z = 0.48 (P = 0.63)
3904
3948
Total (95% CI)
Total events: 92 (Treatment), 53 (Control)
Test for heterogeneity: Chi² = 9.69, df = 12 (P = 0.64), I² = 0%
Test for overall effect: Z = 3.24 (P = 0.001)
0.01
3
4
73.63
0.20 [0.01, 4.15]
3.15 [0.13, 75.08]
0.49 [0.05, 5.35]
1.09 [0.07, 17.06]
Not estimable
Not estimable
Not estimable
0.93 [0.24, 3.62]
2.24 [1.46, 3.43]
Not estimable
Not estimable
1.87 [1.28, 2.74]
7.33
1.63
1.84
10.79
1.01
3.78
1.00
1.42
2.78
5.47
3.65
3.68
15.58
Not estimable
0.33 [0.01, 7.92]
1.02 [0.21, 4.94]
3.04 [0.62, 14.90]
0.50 [0.05, 5.34]
1.25 [0.51, 3.05]
7.61
55.09
02 'Medium' dose
4/153
4/154
AGNELLI1998
3/134
1/169
HO1999
1/85
1/85
SAMAMA1997
372
408
Subtotal (95% CI)
Total events: 8 (Treatment), 6 (Control)
Test for heterogeneity: Chi² = 1.03, df = 2 (P = 0.60), I² = 0%
Test for overall effect: Z = 0.67 (P = 0.50)
100.00
0.1
Favours LMWH
1
10
RR (fixed)
95% CI
[0.26,
[0.40,
[0.06,
[0.51,
3.95]
35.96]
15.73]
4.01]
1.73 [1.24, 2.40]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
597 of 648
DRAFT FOR CONSULTATION
1
LMWH extended duration
2
Figure 136. LMWH extended duration – DVT
Review:
VTE Heparins
Comparison: 03 LMWH extended duration
Outcome: 01 DVT
Study
or sub-category
BERGQVIST1996B
BERGQVIST2002D
COMP2001
DAHL1997
HULL2000A
KOLB2003
LASSEN1998
LAUSEN1998A
MANGANELLI1998A
PLANES1996
TINCAN2005
LMWH
n/N
Nil
n/N
21/117
8/165
48/307
11/93
14/291
7/146
5/113
3/58
4/33
6/85
0/104
RR (fixed)
95% CI
Weight
%
45/116
20/167
76/282
23/89
14/133
17/127
12/102
6/60
6/28
17/88
1/105
18.19
8.00
31.89
9.46
7.74
7.32
5.08
2.37
2.61
6.72
0.60
1512
1297
Total (95% CI)
Total events: 127 (LMWH), 237 (Nil)
Test for heterogeneity: Chi² = 2.75, df = 10 (P = 0.99), I² = 0%
Test for overall effect: Z = 7.27 (P < 0.00001)
100.00
0.01
3
4
0.1
1
Favours LMWH
10
RR (fixed)
95% CI
0.46
0.40
0.58
0.46
0.46
0.36
0.38
0.52
0.57
0.37
0.34
[0.30,
[0.18,
[0.42,
[0.24,
[0.22,
[0.15,
[0.14,
[0.14,
[0.18,
[0.15,
[0.01,
0.73]
0.89]
0.80]
0.88]
0.93]
0.84]
1.03]
1.97]
1.81]
0.88]
8.17]
0.48 [0.39, 0.58]
100
Favours nil
Figure 137. LMWH extended duration – pulmonary embolism
Review:
VTE Heparins
Comparison: 03 LMWH extended duration
Outcome:
02 Pulmonary embolism
Study
or sub-category
BERGQVIST1996B
BERGQVIST2002D
COMP2001
DAHL1997
KOLB2003
LASSEN1998
PLANES1996
TINCAN2005
LMWH
n/N
0/177
0/165
0/441
0/111
0/147
0/140
0/90
0/104
Nil
n/N
RR (fixed)
95% CI
Weight
%
2/166
1/167
3/432
3/106
2/127
0/141
0/89
0/105
1375
1333
Total (95% CI)
Total events: 0 (LMWH), 11 (Nil)
Test for heterogeneity: Chi² = 0.21, df = 4 (P = 0.99), I² = 0%
Test for overall effect: Z = 2.54 (P = 0.01)
0.01
5
0.1
Favours LMWH
1
10
RR (fixed)
95% CI
18.60
10.75
25.50
25.81
19.33
0.19 [0.01, 3.88]
0.34 [0.01, 8.22]
0.14 [0.01, 2.70]
0.14 [0.01, 2.61]
0.17 [0.01, 3.57]
Not estimable
Not estimable
Not estimable
100.00
0.18 [0.05, 0.67]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
598 of 648
DRAFT FOR CONSULTATION
1
Figure 138. LMWH extended duration – proximal DVT
2
Review:
VTE Heparins
Comparison:03 LMWH extended duration
Outcome: 03 Proximal DVT
Study
or sub-category
BERGQVIST1996B
BERGQVIST2002D
COMP2001
DAHL1997
HULL2000A
KOLB2003
LASSEN1998
LAUSEN1998A
MANGANELLI1998A
PLANES1996
LMWH
n/N
Nil
n/N
8/117
1/165
13/307
10/114
3/308
2/146
1/111
0/58
1/33
5/85
RR (fixed)
95% CI
Weight
%
28/116
3/167
31/282
14/104
7/146
17/147
5/101
0/60
5/28
7/88
23.04
2.44
26.48
12.00
7.78
13.88
4.29
1444
1239
Total (95% CI)
Total events: 44 (LMWH), 117 (Nil)
Test for heterogeneity: Chi² = 8.36, df = 8 (P = 0.40), I² = 4.3%
Test for overall effect: Z = 6.28 (P < 0.00001)
0.01
3
4
0.1
1
Favours LMWH
10
RR (fixed)
95% CI
4.43
5.64
0.28 [0.13, 0.60]
0.34 [0.04, 3.21]
0.39 [0.21, 0.72]
0.65 [0.30, 1.40]
0.20 [0.05, 0.77]
0.12 [0.03, 0.50]
0.18 [0.02, 1.53]
Not estimable
0.17 [0.02, 1.37]
0.74 [0.24, 2.24]
100.00
0.34 [0.25, 0.48]
100
Favours nil
Figure 139. LMWH extended duration – major bleed
Review:
VTE Heparins
Comparison:03 LMWH extended duration
Outcome: 05 Major bleed
Study
or sub-category
BERGQVIST2002D
MANGANELLI1998A
TINCAN2005
LMWH
n/N
3/253
0/33
0/104
390
Total (95% CI)
Total events: 3 (LMWH), 1 (Nil)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.96 (P = 0.34)
Nil
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
1/255
0/33
0/105
100.00
3.02 [0.32, 28.87]
Not estimable
Not estimable
393
100.00
3.02 [0.32, 28.87]
0.01
5
6
7
Weight
%
0.1
Favours LMWH
1
10
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
599 of 648
DRAFT FOR CONSULTATION
1
LMWH vs UFH
2
Figure 140. LMWH vs UFH - DVT
Review:
VTE Heparins
Comparison:08 LMWH vs UFH
Outcome: 01 DVT
Study
or sub-category
ADOLF1989
AVIKAINEN1995
BARBUI1990
BAUMGARTNER1989
BEGHI1993
BERGQVIST1986A
BERGQVIST1990A
BERGQVIST1997B
BONEU1993
BORSTAD1988
BRIEL1988
CAEN1988
COLWELL1994
COLWELL1995
CREPERIO1990
DAHAN1989
DECHAVANNE1989
ENKE1988
ERIKSSON1991A
EURIN1994
FARKAS1993
FAUNO1994
FREICK1991
FRICKER1988
GARCEA1992
GAZZANIGA1993
GHAT1992
GODWIN1993
GONZALEZ1996
HAAS1987
HARTL1990
HEILMANN1989
HEILMANN1998
HORBACH1996
KAKKAR1985
KAKKAR1989
KAKKAR2000
KOLLER1986 ii
KOPPENHAGAN1990
KOPPENHAGAN1992
LASSEN1988
LASSEN1989
LASTORIA2006
LEGNANI1990
LEIZOROVICZ1991
LEVINE1991
LIMMER1994
MCLEOD2001
MONREAL1989A
NURMOHAMED1995A
ONARHEIM1986
PLANES1990A
REILMAN1989
SAMAMA1994 III
SAMAMA1994 i
SAMAMA1994 ii
SASAHARA1986
SCHIELKE1991
SCHMITZHUEBNER1984
SENARAN2006
VERARDI1989
VOIGT1986
VONTEMPELHOFF2000
WARD1998A
WELZEL1988
LMWH
n/N
9/202
1/79
45/312
2/27
0/20
6/87
13/215
27/960
30/648
0/105
1/95
6/195
36/136
54/145
5/20
0/46
6/82
28/505
19/67
1/240
10/122
21/92
5/55
0/40
0/45
2/561
45/169
0/595
0/84
15/80
5/112
2/150
10/160
17/142
5/196
8/88
9/101
2/70
4/51
24/323
35/118
14/68
4/41
5/24
23/861
50/333
3/103
44/468
14/46
42/718
1/25
15/124
8/68
4/137
6/159
3/106
14/134
0/47
3/81
0/50
1/44
1/103
10/160
0/271
4/98
UFH
n/N
RR (fixed)
95% CI
6/202
4/79
58/319
2/33
0/19
7/89
9/217
42/936
28/663
0/110
1/98
7/190
21/142
74/143
3/20
0/41
4/40
41/497
25/69
0/239
4/111
25/93
12/55
0/40
1/40
5/561
47/172
3/309
0/82
15/80
5/115
6/150
10/164
14/147
14/199
10/91
24/116
1/68
7/53
26/330
34/122
23/71
4/34
5/26
7/429
61/332
3/100
44/468
6/44
25/709
0/27
27/113
6/71
5/133
12/158
3/110
13/126
0/51
0/39
2/50
3/44
1/97
10/164
1/281
14/103
0.69
0.46
6.55
0.21
11809
11024
Total (95% CI)
Total events: 777 (LMWH), 870 (UFH)
Test for heterogeneity: Chi² = 69.86, df = 58 (P = 0.14), I² = 17.0%
Test for overall effect: Z = 2.78 (P = 0.005)
100.00
0.01
3
Weight
%
0.79
1.02
4.86
3.16
0.11
0.81
2.35
8.51
0.34
0.61
4.72
2.81
0.06
0.48
2.84
1.37
0.18
0.57
5.32
0.53
1.71
0.56
0.69
1.13
1.57
1.59
1.12
2.55
0.12
0.78
2.94
3.82
2.57
0.50
0.55
1.07
6.98
0.35
5.03
0.70
2.87
0.06
3.23
0.67
0.58
1.38
0.34
1.53
0.08
0.29
0.34
0.12
1.13
0.17
1.56
0.1
Favours LMWH
1
10
RR (fixed)
95% CI
1.50 [0.54, 4.14]
0.25 [0.03, 2.19]
0.79 [0.56, 1.13]
1.22 [0.18, 8.11]
Not estimable
0.88 [0.31, 2.50]
1.46 [0.64, 3.34]
0.63 [0.39, 1.01]
1.10 [0.66, 1.81]
Not estimable
1.03 [0.07, 16.26]
0.84 [0.29, 2.44]
1.79 [1.10, 2.90]
0.72 [0.55, 0.94]
1.67 [0.46, 6.06]
Not estimable
0.73 [0.22, 2.45]
0.67 [0.42, 1.07]
0.78 [0.48, 1.28]
2.99 [0.12, 72.97]
2.27 [0.73, 7.05]
0.85 [0.51, 1.40]
0.42 [0.16, 1.10]
Not estimable
0.30 [0.01, 7.09]
0.40 [0.08, 2.05]
0.97 [0.69, 1.38]
0.07 [0.00, 1.43]
Not estimable
1.00 [0.52, 1.91]
1.03 [0.31, 3.45]
0.33 [0.07, 1.63]
1.03 [0.44, 2.40]
1.26 [0.64, 2.45]
0.36 [0.13, 0.99]
0.83 [0.34, 2.00]
0.43 [0.21, 0.88]
1.94 [0.18, 20.93]
0.59 [0.18, 1.91]
0.94 [0.55, 1.61]
1.06 [0.71, 1.59]
0.64 [0.36, 1.13]
0.83 [0.22, 3.07]
1.08 [0.36, 3.28]
1.64 [0.71, 3.78]
0.82 [0.58, 1.15]
0.97 [0.20, 4.70]
1.00 [0.67, 1.49]
2.23 [0.94, 5.29]
1.66 [1.02, 2.69]
3.23 [0.14, 75.83]
0.51 [0.28, 0.90]
1.39 [0.51, 3.80]
0.78 [0.21, 2.83]
0.50 [0.19, 1.29]
1.04 [0.21, 5.03]
1.01 [0.50, 2.07]
Not estimable
3.41 [0.18, 64.52]
0.20 [0.01, 4.06]
0.33 [0.04, 3.08]
0.94 [0.06, 14.85]
1.03 [0.44, 2.40]
0.35 [0.01, 8.45]
0.30 [0.10, 0.88]
0.88 [0.81, 0.96]
100
Favours UFH
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
600 of 648
DRAFT FOR CONSULTATION
1
2
Figure 141. LMWH vs UFH – pulmonary embolism
Review:
VTE Heparins
Comparison:08 LMWH vs UFH
Outcome: 02 Pulmonary embolism
Study
or sub-category
AVIKAINEN1995
BERGQVIST1990A
BONEU1993
BORSTAD1988
CAEN1988
CATANIA1988
COLWELL1995
ERIKSSON1991A
FARKAS1993
FAUNO1994
FREICK1991
FRICKER1988
GARCEA1992
GAZZANIGA1993
GHAT1992
HAAS1987
HEILMANN1989
HOFFMANN1992
HORBACH1996
KAAJA1992
KAKKAR1985
KAKKAR2000
KOPPENHAGAN1992
LASSEN1989
LEVINE1991
LIMMER1994
MCLEOD2001
MONREAL1989A
NURMOHAMED1995A
PLANES1990A
SALCUNI1988
SAMAMA1994 III
SAMAMA1994 i
SAMAMA1994 ii
WARD1998A
LMWH
n/N
0/84
0/505
1/648
0/105
0/195
0/88
0/145
8/65
0/122
0/92
0/55
0/40
0/45
2/561
2/167
0/80
7/160
1/298
0/142
0/37
0/196
1/125
3/323
1/53
0/332
0/103
1/468
6/46
0/718
0/124
0/73
0/157
0/167
0/124
5/271
UFH
n/N
RR (fixed)
95% CI
Weight
%
1/83
5/497
3/663
0/110
0/190
1/85
1/143
19/62
0/111
0/93
1/55
2/40
0/40
2/561
6/168
1/80
4/164
1/296
1/147
0/31
0/199
2/134
2/330
0/54
2/333
0/100
0/468
0/42
1/709
1/113
1/68
1/147
0/167
0/123
1/281
2.24
8.21
4.39
2.26
2.24
28.81
2.22
3.70
2.96
8.86
2.22
5.85
1.49
2.18
2.86
2.93
0.73
3.70
0.74
0.77
2.24
2.32
2.30
2.29
1.45
6914
6887
Total (95% CI)
Total events: 38 (LMWH), 59 (UFH)
Test for heterogeneity: Chi² = 20.78, df = 24 (P = 0.65), I² = 0%
Test for overall effect: Z = 2.09 (P = 0.04)
0.01
3
4
100.00
0.1
Favours LMWH
1
10
RR (fixed)
95% CI
0.33 [0.01, 7.97]
0.09 [0.00, 1.61]
0.34 [0.04, 3.27]
Not estimable
Not estimable
0.32 [0.01, 7.80]
0.33 [0.01, 8.00]
0.40 [0.19, 0.85]
Not estimable
Not estimable
0.33 [0.01, 8.01]
0.20 [0.01, 4.04]
Not estimable
1.00 [0.14, 7.07]
0.34 [0.07, 1.64]
0.33 [0.01, 8.06]
1.79 [0.54, 6.01]
0.99 [0.06, 15.81]
0.34 [0.01, 8.40]
Not estimable
Not estimable
0.54 [0.05, 5.84]
1.53 [0.26, 9.11]
3.06 [0.13, 73.37]
0.20 [0.01, 4.16]
Not estimable
3.00 [0.12, 73.45]
11.89 [0.69, 204.91]
0.33 [0.01, 8.07]
0.30 [0.01, 7.39]
0.31 [0.01, 7.50]
0.31 [0.01, 7.60]
Not estimable
Not estimable
5.18 [0.61, 44.09]
0.68 [0.47, 0.98]
100
Favours UFH
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
601 of 648
DRAFT FOR CONSULTATION
1
Figure 142. LMWH vs UFH – proximal DVT
Review:
VTE Heparins
Comparison: 08 LMWH vs UFH
Outcome:
03 Proximal DVT
Study
or sub-category
AVIKAINEN1995
BONEU1993
CAEN1988
DECHAVANNE1989
ENKE1988
ERIKSSON1991A
FAUNO1994
FREICK1991
GHAT1992
HARTL1990
HORBACH1996
KAKKAR1985
KAKKAR2000
LASSEN1988
LEVINE1991
MONREAL1989A
PLANES1990A
LMWH
n/N
1/79
9/648
1/195
2/77
4/960
6/63
3/92
5/52
14/136
0/112
0/142
1/199
3/101
13/107
16/258
12/46
9/120
UFH
n/N
RR (random)
95% CI
RR (random)
95% CI
4/79
3/663
3/190
3/38
13/936
18/59
5/93
8/48
27/137
0/115
0/147
4/196
5/116
21/112
18/263
5/44
20/106
2.20
5.12
2.05
3.21
6.37
8.91
4.57
6.95
12.40
2.18
4.55
11.80
11.61
7.78
10.31
0.25 [0.03, 2.19]
3.07 [0.83, 11.29]
0.32 [0.03, 3.09]
0.33 [0.06, 1.89]
0.30 [0.10, 0.92]
0.31 [0.13, 0.73]
0.61 [0.15, 2.46]
0.58 [0.20, 1.64]
0.52 [0.29, 0.95]
Not estimable
Not estimable
0.25 [0.03, 2.18]
0.69 [0.17, 2.81]
0.65 [0.34, 1.23]
0.91 [0.47, 1.74]
2.30 [0.88, 5.98]
0.40 [0.19, 0.83]
3387
3342
Total (95% CI)
Total events: 99 (LMWH), 157 (UFH)
Test for heterogeneity: Chi² = 22.31, df = 14 (P = 0.07), I² = 37.2%
Test for overall effect: Z = 2.84 (P = 0.004)
100.00
0.61 [0.43, 0.86]
0.01
2
3
Weight
%
0.1
Favours LMWH
1
10
100
Favours UFH
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
602 of 648
DRAFT FOR CONSULTATION
1
Figure 143. LMWH vs UFH – major bleed
Review:
VTE Heparins
Comparison:08 LMWH vs UFH
Outcome: 04 Major bleed
Study
or sub-category
BAUMGARTNER1989
BERGQVIST1986A
BERGQVIST1997B
BONEU1993
BORSTAD1988
BORSTAD1992
CAEN1988
CATANIA1988
COLWELL1994
COLWELL1995
ERIKSSON1991A
FRICKER1988
GARCEA1992
GAZZANIGA1993
GONZALEZ1996
HAAS1987
HARTL1990
HEILMANN1989
HEILMANN1998
HOFFMANN1992
KAAJA1992
KAKKAR1989
KAKKAR1993
KOLLER1986 i
KOLLER1986 ii
KOPPENHAGAN1990
LASSEN1988
LASTORIA2006
LEIZOROVICZ1991
LEVINE1991
LIMMER1994
MCLEOD2001
NURMOHAMED1995A
ONARHEIM1986
REILMAN1989
SALCUNI1988
SAMAMA1994 III
SAMAMA1994 i
SAMAMA1994 ii
SCHIELKE1991
SCHMITZHUEBNER1984
SENARAN2006
VOIGT1986
LMWH
n/N
0/99
10/215
23/555
48/648
1/105
14/77
0/195
0/88
11/398
3/228
1/67
2/40
0/45
1/561
0/84
3/80
2/126
2/150
27/179
10/298
0/37
2/88
69/1894
1/75
6/23
0/51
1/118
0/41
22/861
11/332
0/103
18/653
11/737
1/25
1/68
6/73
1/160
1/168
1/127
1/47
2/84
2/50
3/103
UFH
n/N
RR (fixed)
95% CI
Weight
%
0/102
3/217
16/560
48/663
1/110
9/75
1/190
0/85
13/209
3/225
5/69
1/40
7/45
2/561
5/82
1/80
3/124
3/150
47/179
7/296
6/31
0/91
91/1915
0/75
2/20
0/53
1/122
0/34
14/429
19/333
0/100
10/643
18/734
1/27
3/71
5/68
1/147
1/167
0/123
0/51
0/42
0/50
1/97
0.83
4.40
13.11
0.27
2.52
0.42
4.71
0.83
1.36
0.28
2.07
0.55
1.54
0.28
0.84
0.83
12.99
1.94
1.95
0.14
25.01
0.14
0.59
0.27
5.16
5.24
2.79
4.98
0.27
0.81
1.43
0.29
0.28
0.14
0.13
0.18
0.14
0.28
10156
9485
Total (95% CI)
Total events: 318 (LMWH), 348 (UFH)
Test for heterogeneity: Chi² = 45.12, df = 37 (P = 0.17), I² = 18.0%
Test for overall effect: Z = 2.01 (P = 0.04)
0.01
2
3
100.00
0.1
Favours LMWH
1
10
RR (fixed)
95% CI
Not estimable
3.36 [0.94, 12.06]
1.45 [0.77, 2.72]
1.02 [0.70, 1.50]
1.05 [0.07, 16.53]
1.52 [0.70, 3.29]
0.32 [0.01, 7.92]
Not estimable
0.44 [0.20, 0.97]
0.99 [0.20, 4.84]
0.21 [0.02, 1.72]
2.00 [0.19, 21.18]
0.07 [0.00, 1.13]
0.50 [0.05, 5.50]
0.09 [0.00, 1.58]
3.00 [0.32, 28.23]
0.66 [0.11, 3.86]
0.67 [0.11, 3.93]
0.57 [0.38, 0.88]
1.42 [0.55, 3.68]
0.06 [0.00, 1.11]
5.17 [0.25, 106.16]
0.77 [0.56, 1.04]
3.00 [0.12, 72.49]
2.61 [0.59, 11.50]
Not estimable
1.03 [0.07, 16.34]
Not estimable
0.78 [0.40, 1.51]
0.58 [0.28, 1.20]
Not estimable
1.77 [0.82, 3.81]
0.61 [0.29, 1.28]
1.08 [0.07, 16.36]
0.35 [0.04, 3.26]
1.12 [0.36, 3.49]
0.92 [0.06, 14.56]
0.99 [0.06, 15.76]
2.91 [0.12, 70.66]
3.25 [0.14, 77.88]
2.53 [0.12, 51.53]
5.00 [0.25, 101.58]
2.83 [0.30, 26.70]
0.86 [0.74, 1.00]
100
Favours UFH
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
603 of 648
DRAFT FOR CONSULTATION
1
Fondaparinux vs LMWH
2
Figure 144. Fondaparinux vs LMWH – DVT
Review:
VTE Fondaparinux
Comparison: 01 Fondaparinux vs LMWH
Outcome:
01 DVT
Study
or sub-category
AGNELLI2005
BAUER2001
ERIKSSON2001
LASSEN2002
TURPIE2002K
Fondaparinux
n/N
43/1024
45/361
49/624
36/908
44/784
LMWH
n/N
RR (random)
95% CI
Weight
%
18.38
21.80
22.21
18.53
19.08
59/1018
98/361
117/623
83/918
65/796
3701
3716
Total (95% CI)
Total events: 217 (Fondaparinux), 422 (LMWH)
Test for heterogeneity: Chi² = 8.25, df = 4 (P = 0.08), I² = 51.5%
Test for overall effect: Z = 5.61 (P < 0.00001)
0.01
3
4
100.00
0.1
1
10
Favours fondaparinux
RR (random)
95% CI
0.72
0.46
0.42
0.44
0.69
[0.49,
[0.33,
[0.31,
[0.30,
[0.47,
1.06]
0.63]
0.57]
0.64]
0.99]
0.52 [0.42, 0.66]
100
Favours LMWH
Figure 145. Fondaparinux vs LMWH – pulmonary embolism
Review:
VTE Fondaparinux
Comparison: 01 Fondaparinux vs LMWH
Outcome:
02 Pulmonary embolism
Study
or sub-category
BAUER2001
ERIKSSON2001
LASSEN2002
TURPIE2002K
Fondaparinux
n/N
LMWH
n/N
1/517
3/831
2/1129
5/1126
RR (fixed)
95% CI
Weight
%
4/517
3/840
2/1123
1/1128
40.05
29.87
20.08
10.00
3603
3608
Total (95% CI)
Total events: 11 (Fondaparinux), 10 (LMWH)
Test for heterogeneity: Chi² = 3.70, df = 3 (P = 0.30), I² = 18.9%
Test for overall effect: Z = 0.22 (P = 0.82)
0.01
5
6
100.00
0.1
1
Favours fondaparinux
10
RR (fixed)
95% CI
0.25
1.01
0.99
5.01
[0.03,
[0.20,
[0.14,
[0.59,
2.23]
4.99]
7.05]
42.81]
1.10 [0.47, 2.59]
100
Favours LMWH
Figure 146. Fondaparinux vs LMWH – proximal DVT
Review:
VTE Fondaparinux
Comparison: 01 Fondaparinux vs LMWH
Outcome:
03 Proximal DVT
Study
or sub-category
Fondaparinux
n/N
AGNELLI2005
5/1076
1076
Total (95% CI)
Total events: 5 (Fondaparinux), 5 (LMWH)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.00 (P = 1.00)
LMWH
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
5/1077
100.00
1.00 [0.29, 3.45]
1077
100.00
1.00 [0.29, 3.45]
0.01
7
Weight
%
0.1
Favours fondaparinux
1
10
100
Favours LMWH
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
604 of 648
DRAFT FOR CONSULTATION
1
Figure 147. Fondaparinux vs LMWH – major bleed
Review:
VTE Fondaparinux
Comparison:01 Fondaparinux vs LMWH
Outcome: 04 Major bleed
Study
or sub-category
AGNELLI2005
Fondaparinux
n/N
49/1433
LMWH
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
34/1425
100.00
1.43 [0.93, 2.21]
1425
100.00
1.43 [0.93, 2.21]
1433
Total (95% CI)
Total events: 49 (Fondaparinux), 34 (LMWH)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.64 (P = 0.10)
0.01
2
3
4
Weight
%
0.1
1
Favours fondaparinux
10
100
Favours LMWH
5
Fondaparinux extended durtation
6
Figure 148. Fondaparinux extended duration – DVT
Review:
VTE Fondaparinux
Comparison:02 Fondaparinux - extended duration
Outcome: 01 DVT
Study
or sub-category
ERIKSSON2003A
Fondaparinux
n/N
3/208
Control
n/N
RR (fixed)
95% CI
100.00
0.04 [0.01, 0.13]
218
100.00
0.04 [0.01, 0.13]
0.01
8
RR (fixed)
95% CI
74/218
208
Total (95% CI)
Total events: 3 (Fondaparinux), 74 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 5.44 (P < 0.00001)
7
Weight
%
0.1
1
Favours fondaparinux
10
100
Favours control
Figure 149. Fondaparinux extended duration – pulmonary embolism
Review:
VTE Fondaparinux
Comparison:02 Fondaparinux - extended duration
Outcome: 02 Pulmonary embolism
Study
or sub-category
ERIKSSON2003A
Treatment
n/N
1/326
326
Total (95% CI)
Total events: 1 (Treatment), 9 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 2.08 (P = 0.04)
Control
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
9/330
100.00
0.11 [0.01, 0.88]
330
100.00
0.11 [0.01, 0.88]
0.01
9
Weight
%
0.1
Favours treatment
1
10
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
605 of 648
DRAFT FOR CONSULTATION
1
Figure 150. Fondaparinux extended duration – proximal DVT
Review:
VTE Fondaparinux
Comparison:02 Fondaparinux - extended duration
Outcome: 03 Proximal DVT
Study
or sub-category
ERIKSSON2003A
Fondaparinux
n/N
2/221
Control
n/N
RR (fixed)
95% CI
100.00
0.06 [0.01, 0.24]
222
100.00
0.06 [0.01, 0.24]
0.01
3
RR (fixed)
95% CI
35/222
221
Total (95% CI)
Total events: 2 (Fondaparinux), 35 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 3.96 (P < 0.0001)
2
Weight
%
0.1
1
Favours fondaparinux
10
100
Favours control
Figure 151. Fondaparinux extended duration – major bleed
Review:
VTE Fondaparinux
Comparison:02 Fondaparinux - extended duration
Outcome: 04 Major Bleed
Study
or sub-category
ERIKSSON2003A
Fondaparinux
n/N
6/327
327
Total (95% CI)
Total events: 6 (Fondaparinux), 0 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.75 (P = 0.08)
Control
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
0/329
100.00
13.08 [0.74, 231.23]
329
100.00
13.08 [0.74, 231.23]
0.01
4
5
6
7
8
Weight
%
0.1
Favours fondaparinux
1
10
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
606 of 648
DRAFT FOR CONSULTATION
1
Antiplatelet therapy vs no prophylaxis
2
Figure 152. Antiplatelet vs no prophylaxis – DVT
Review:
VTE Aspirin
Comparison:02 Antiplatelet vs no prophylaxis - subgrouped by antiplatelet therapy
Outcome: 01 DVT
Study
or sub-category
Antiplatelet Therapy
n/N
No prophylaxis
n/N
RR (random)
95% CI
Weight
%
01 Aspirin v nil
3/60
11/30
ALFARO1986
9/56
11/49
CLAGETT1975
11/58
23/59
HARRIS1977
8/24
9/12
MCKENNA1980
42/153
33/150
MRC1972
27/66
29/63
POWERS1989
16/44
20/44
SCHREIBER1979 ii
7/138
17/140
ZEKERT1975A
16/50
12/50
ZEKERT1982
649
597
Subtotal (95% CI)
Total events: 139 (Antiplatelet Therapy), 165 (No prophylaxis)
Test for heterogeneity: Chi² = 23.91, df = 8 (P = 0.002), I² = 66.5%
Test for overall effect: Z = 2.11 (P = 0.03)
02 Aspirin + other antiplatelet v nil
3/21
4/11
BOEHRINGER1976
10/20
8/20
DECHAVANNE1975
12/21
4/9
ENCKE1976 i
12/62
13/34
ENCKE1976 ii
14/34
8/25
ENCKE1976 iii
8/21
8/22
MCBRIDE1975
15/24
16/24
MORRIS1977 i
20/32
21/32
MORRIS1977 ii
13/75
35/75
OSULLIVAN1972
6/40
9/22
PARODI1973 i
16/91
13/35
PARODI1973 ii
3/38
14/66
PLANTE1979
12/85
24/75
RENNEY1976
33/68
52/77
SAUTTER1983
23/64
17/68
SILBERG1978
1/30
11/36
WEISS1977
20/21
6/9
WOOD1973
1/46
6/44
WU1977
54/135
16/46
ZEKERT1975 i
928
730
Subtotal (95% CI)
Total events: 276 (Antiplatelet Therapy), 285 (No prophylaxis)
Test for heterogeneity: Chi² = 49.95, df = 18 (P < 0.0001), I² = 64.0%
Test for overall effect: Z = 2.24 (P = 0.03)
03 Other antiplatelet therapies v nil
7/48
14/48
ARAPAKIS1981
0/284
25/281
CARTER1971 i
5/107
17/97
CARTER1974
24/48
33/50
HANSEN1976 i
7/27
18/28
HANSEN1976 ii
10/20
10/20
HUME1977
36/48
39/46
HURLOW1983
12/18
11/17
JOHANSSON1981
8/40
12/40
LASIERRA1982
14/29
16/29
MCKENNA1983
13/20
12/20
MORRIS1977 iii
8/20
13/20
REVOL1977
17/68
12/68
TURPIE1985
20/120
14/118
VETH1985
7/31
9/33
WALKER1983
1/46
6/44
WU1977
974
959
Subtotal (95% CI)
Total events: 189 (Antiplatelet Therapy), 261 (No prophylaxis)
Test for heterogeneity: Chi² = 35.41, df = 15 (P = 0.002), I² = 57.6%
Test for overall effect: Z = 2.14 (P = 0.03)
2551
2286
Total (95% CI)
Total events: 604 (Antiplatelet Therapy), 711 (No prophylaxis)
Test for heterogeneity: Chi² = 107.75, df = 43 (P < 0.00001), I² = 60.1%
Test for overall effect: Z = 3.82 (P = 0.0001)
0.01
3
4
1.09
1.90
2.45
2.34
3.36
3.37
2.89
1.75
2.39
21.55
0.14
0.72
0.49
0.44
1.25
0.89
0.80
0.42
1.33
0.69
[0.04,
[0.32,
[0.26,
[0.23,
[0.84,
[0.60,
[0.48,
[0.18,
[0.70,
[0.48,
0.45]
1.58]
0.90]
0.85]
1.85]
1.32]
1.33]
0.98]
2.52]
0.97]
0.95
2.20
1.83
2.30
2.18
1.95
3.26
3.49
2.72
1.65
2.46
1.11
2.46
3.82
2.82
0.47
3.04
0.43
3.15
42.29
0.39
1.25
1.29
0.51
1.29
1.05
0.94
0.95
0.37
0.37
0.47
0.37
0.44
0.72
1.44
0.11
1.43
0.16
1.15
0.76
[0.11,
[0.63,
[0.57,
[0.26,
[0.64,
[0.48,
[0.62,
[0.66,
[0.21,
[0.15,
[0.25,
[0.11,
[0.24,
[0.54,
[0.85,
[0.01,
[0.89,
[0.02,
[0.74,
[0.60,
1.45]
2.50]
2.92]
0.98]
2.59]
2.28]
1.43]
1.38]
0.64]
0.90]
0.88]
1.21]
0.82]
0.96]
2.43]
0.80]
2.29]
1.27]
1.80]
0.97]
1.84
0.25
1.50
3.58
2.20
2.45
4.15
3.01
1.94
2.92
3.00
2.43
2.32
2.40
1.73
0.43
36.16
0.50
0.02
0.27
0.76
0.40
1.00
0.88
1.03
0.67
0.88
1.08
0.62
1.42
1.40
0.83
0.16
0.78
[0.22,
[0.00,
[0.10,
[0.54,
[0.20,
[0.54,
[0.72,
[0.64,
[0.31,
[0.53,
[0.67,
[0.33,
[0.73,
[0.75,
[0.35,
[0.02,
[0.62,
1.13]
0.32]
0.70]
1.07]
0.81]
1.86]
1.08]
1.66]
1.45]
1.44]
1.75]
1.15]
2.74]
2.65]
1.95]
1.27]
0.98]
100.00
0.1
Favours antiplatelet
1
10
RR (random)
95% CI
0.76 [0.65, 0.87]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
607 of 648
DRAFT FOR CONSULTATION
1
2
Figure 153. Antiplatelet vs no prophylaxis – proximal DVT
Review:
VTE Aspirin
Comparison: 02 Antiplatelet vs no prophylaxis - subgrouped by antiplatelet therapy
Outcome: 03 Proximal DVT
Study
or sub-category
Antilplatelet
n/N
no prophylaxis
n/N
RR (fixed)
95% CI
Weight
%
01 Aspirin v nil
5/58
14/59
HARRIS1977
2/24
3/12
MCKENNA1980
7/66
19/63
POWERS1989
3/50
0/50
ZEKERT1982
198
184
Subtotal (95% CI)
Total events: 17 (Antilplatelet), 36 (no prophylaxis)
Test for heterogeneity: Chi² = 3.99, df = 3 (P = 0.26), I² = 24.8%
Test for overall effect: Z = 3.02 (P = 0.003)
02 Aspirin + other antiplatelet v nil
1/91
2/35
PARODI1973 ii
13/68
29/77
SAUTTER1983
16/21
5/9
WOOD1973
180
121
Subtotal (95% CI)
Total events: 30 (Antilplatelet), 36 (no prophylaxis)
Test for heterogeneity: Chi² = 7.16, df = 2 (P = 0.03), I² = 72.1%
Test for overall effect: Z = 2.04 (P = 0.04)
04 Other antiplatelet therapies v nil
0/107
1/97
CARTER1974
14/48
12/46
HURLOW1983
2/40
4/40
LASIERRA1982
2/68
3/68
TURPIE1985
263
251
Subtotal (95% CI)
Total events: 18 (Antilplatelet), 20 (no prophylaxis)
Test for heterogeneity: Chi² = 1.50, df = 3 (P = 0.68), I² = 0%
Test for overall effect: Z = 0.47 (P = 0.64)
641
556
Total (95% CI)
Total events: 65 (Antilplatelet), 92 (no prophylaxis)
Test for heterogeneity: Chi² = 17.24, df = 10 (P = 0.07), I² = 42.0%
Test for overall effect: Z = 3.36 (P = 0.0008)
0.01
3
4
14.50
4.18
20.31
0.52
39.51
0.36
0.33
0.35
7.00
0.44
[0.14,
[0.06,
[0.16,
[0.37,
[0.26,
0.94]
1.73]
0.78]
132.10]
0.75]
3.02
28.41
7.31
38.74
0.19
0.51
1.37
0.65
[0.02,
[0.29,
[0.73,
[0.42,
2.05]
0.89]
2.58]
0.98]
1.64
12.80
4.18
3.13
21.76
0.30
1.12
0.50
0.67
0.87
[0.01,
[0.58,
[0.10,
[0.12,
[0.50,
7.34]
2.16]
2.58]
3.86]
1.53]
100.00
0.1
Favours antiplatelet
1
10
RR (fixed)
95% CI
0.61 [0.46, 0.82]
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
608 of 648
DRAFT FOR CONSULTATION
1
Figure 154. Antiplatelet vs no prophylaxis – major bleed
Review:
VTE Aspirin
Comparison:02 Antiplatelet vs no prophylaxis - subgrouped by antiplatelet therapy
Outcome: 04 Major bleed
Study
or sub-category
Antiplatelet Therapy
n/N
No Prophylaxis
n/N
RR (fixed)
95% CI
Weight
%
01 Aspirin v nil
0/60
0/30
ALFARO1986
0/56
0/49
CLAGETT1975
0/58
0/59
HARRIS1977
0/702
0/679
LOEW1974A
1/24
0/12
MCKENNA1980
1/66
1/63
POWERS1989
3/357
0/357
SCHREIBER1979 i
0/44
0/44
SCHREIBER1979 ii
0/26
0/25
SOREFF1975
0/138
2/140
ZEKERT1975A
0/50
0/50
ZEKERT1982
1581
1508
Subtotal (95% CI)
Total events: 5 (Antiplatelet Therapy), 3 (No Prophylaxis)
Test for heterogeneity: Chi² = 2.75, df = 3 (P = 0.43), I² = 0%
Test for overall effect: Z = 0.41 (P = 0.68)
4.37
6.80
3.32
16.49
30.98
02 Aspirin + other antiplatelet v nil
1/21
0/11
BOEHRINGER1976
0/20
0/20
DECHAVANNE1975
0/21
0/9
ENCKE1976 i
0/62
0/34
ENCKE1976 ii
0/34
0/25
ENCKE1976 iii
0/300
0/100
HARJOLA1980
0/24
0/24
MORRIS1977 i
0/32
0/32
MORRIS1977 ii
0/91
0/35
PARODI1973 ii
0/38
0/66
PLANTE1979
0/85
0/75
RENNEY1976
0/68
0/77
SAUTTER1983
7/50
3/25
SNOOK1981
0/30
0/36
WEISS1977
0/21
0/9
WOOD1973
3/135
0/46
ZEKERT1975 i
1032
624
Subtotal (95% CI)
Total events: 11 (Antiplatelet Therapy), 3 (No Prophylaxis)
Test for heterogeneity: Chi² = 0.22, df = 2 (P = 0.90), I² = 0%
Test for overall effect: Z = 0.60 (P = 0.55)
4.30
26.57
4.94
35.81
04 Other antiplatelet therapies v nil
0/48
0/48
ARAPAKIS1981
0/107
0/97
CARTER1974
2/51
2/51
CHRISMAN1976
0/25
0/25
COOKE1977
0/48
0/50
HANSEN1976 i
0/27
0/28
HANSEN1976 ii
0/20
0/20
HUME1977
0/18
0/17
JOHANSSON1981
0/29
0/29
MCKENNA1983
0/20
0/20
MORRIS1977 iii
0/50
0/58
PILCHER1975
0/20
0/20
REVOL1977
4/68
3/68
TURPIE1985
0/120
0/118
VETH1985
651
649
Subtotal (95% CI)
Total events: 6 (Antiplatelet Therapy), 5 (No Prophylaxis)
Test for heterogeneity: Chi² = 0.05, df = 1 (P = 0.82), I² = 0%
Test for overall effect: Z = 0.31 (P = 0.76)
0.01
2
0.1
1
10
1.64 [0.07, 37.15]
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
1.17 [0.33, 4.13]
Not estimable
Not estimable
2.42 [0.13, 45.97]
1.40 [0.47, 4.15]
33.21
100.00
1.30 [0.67, 2.52]
19.93
Favours antiplatelet
Not estimable
Not estimable
Not estimable
Not estimable
1.56 [0.07, 35.67]
0.95 [0.06, 14.93]
7.00 [0.36, 135.03]
Not estimable
Not estimable
0.20 [0.01, 4.19]
Not estimable
1.29 [0.38, 4.32]
Not estimable
Not estimable
1.00 [0.15, 6.83]
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
1.33 [0.31, 5.73]
Not estimable
1.20 [0.38, 3.82]
13.29
3264
2781
Total (95% CI)
Total events: 22 (Antiplatelet Therapy), 11 (No Prophylaxis)
Test for heterogeneity: Chi² = 3.04, df = 8 (P = 0.93), I² = 0%
Test for overall effect: Z = 0.77 (P = 0.44)
RR (fixed)
95% CI
100
Favours nil
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
609 of 648
DRAFT FOR CONSULTATION
1
Aspirin as an adjuvant
2
Figure 155. Aspirin adjuvant - DVT
Review:
VTE Aspirin
Comparison: 03 Aspirin adjuvant
Outcome:
01 DVT
Study
or sub-category
Aspirin adjuvant
n/N
Control
n/N
RR (fixed)
95% CI
Weight
%
01 Aspirin + heparin v heparin
4/20
4/20
FLICOTEAUX1977
5/62
11/62
LOEW1977
27/151
27/154
MONREAL1995
12/50
16/49
ZEKERT1980
283
285
Subtotal (95% CI)
Total events: 48 (Aspirin adjuvant), 58 (Control)
Test for heterogeneity: Chi² = 2.32, df = 3 (P = 0.51), I² = 0%
Test for overall effect: Z = 1.05 (P = 0.29)
02 Aspirin + dipyridamole v dipyridamole
2/21
4/19
PARODI1973 i
3/31
6/30
PARODI1973 iv
6/17
8/19
ZEKERT1975 i
69
68
Subtotal (95% CI)
Total events: 11 (Aspirin adjuvant), 18 (Control)
Test for heterogeneity: Chi² = 0.79, df = 2 (P = 0.67), I² = 0%
Test for overall effect: Z = 1.42 (P = 0.16)
352
353
Total (95% CI)
Total events: 59 (Aspirin adjuvant), 76 (Control)
Test for heterogeneity: Chi² = 3.50, df = 6 (P = 0.74), I² = 0%
Test for overall effect: Z = 1.58 (P = 0.11)
0.01
5
5.28
14.52
35.29
21.34
76.43
1.00
0.45
1.02
0.74
0.83
[0.29,
[0.17,
[0.63,
[0.39,
[0.59,
3.45]
1.23]
1.65]
1.39]
1.17]
5.54
8.05
9.97
23.57
0.45
0.48
0.84
0.63
[0.09,
[0.13,
[0.36,
[0.33,
2.20]
1.76]
1.93]
1.19]
100.00
3
4
0.1
1
Favours aspirin
10
RR (fixed)
95% CI
0.78 [0.58, 1.06]
100
Favours control
Figure 156. Aspirin adjuvant – pulmonary embolism
Review:
VTE Aspirin
Comparison: 03 Aspirin adjuvant
Outcome: 02 Pulmonary embolism
Study
or sub-category
Aspirin adjuvant
n/N
Control
n/N
RR (fixed)
95% CI
Weight
%
01 Aspirin + unfractionated heparin v unfractionated heparin
8/151
8/154
MONREAL1995
151
154
Subtotal (95% CI)
Total events: 8 (Aspirin adjuvant), 8 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.04 (P = 0.97)
02 Aspirin + IPC+ GCS v IPC + GCS
1/72
WOOLSON1991
72
Subtotal (95% CI)
Total events: 1 (Aspirin adjuvant), 0 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.71 (P = 0.48)
0/76
76
03 Aspirin adjuvant (variety of additional prophylaxis)
9/2047
10/2041
PEP2000 elective
46/6679
81/6671
PEP2000 hip fracture
8726
8712
Subtotal (95% CI)
Total events: 55 (Aspirin adjuvant), 91 (Control)
Test for heterogeneity: Chi² = 0.86, df = 1 (P = 0.35), I² = 0%
Test for overall effect: Z = 2.97 (P = 0.003)
8949
8942
Total (95% CI)
Total events: 64 (Aspirin adjuvant), 99 (Control)
Test for heterogeneity: Chi² = 2.85, df = 3 (P = 0.42), I² = 0%
Test for overall effect: Z = 2.72 (P = 0.007)
0.01
6
7
0.1
Favours aspirin
1
10
RR (fixed)
95% CI
7.96
7.96
1.02 [0.39, 2.65]
1.02 [0.39, 2.65]
0.49
0.49
3.16 [0.13, 76.44]
3.16 [0.13, 76.44]
10.07
81.48
91.55
0.90 [0.37, 2.20]
0.57 [0.40, 0.81]
0.60 [0.43, 0.84]
100.00
0.65 [0.48, 0.89]
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
610 of 648
DRAFT FOR CONSULTATION
1
Figure 157. Aspirin adjuvant – proximal DVT
Review:
VTE Aspirin
Comparison: 03 Aspirin adjuvant
Outcome:
03 Proximal DVT
Study
or sub-category
Aspirin adjuvant
n/N
Control
n/N
RR (fixed)
95% CI
Weight
%
01 Aspirin + unfractionated heparin v unfractionated heparin
0/20
1/20
FLICOTEAUX1977
0/62
5/62
LOEW1977
14/151
13/154
MONREAL1995
1/350
9/378
VINAZZER1980
5/50
5/49
ZEKERT1980
633
663
Subtotal (95% CI)
Total events: 20 (Aspirin adjuvant), 33 (Control)
Test for heterogeneity: Chi² = 7.22, df = 4 (P = 0.12), I² = 44.6%
Test for overall effect: Z = 1.72 (P = 0.09)
02 Aspirin + dipyridamole v dipyridamole
0/31
PARODI1973 iv
31
Subtotal (95% CI)
Total events: 0 (Aspirin adjuvant), 1 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.70 (P = 0.48)
3.42
12.54
29.35
19.73
11.52
76.56
0.33
0.09
1.10
0.12
0.98
0.63
[0.01,
[0.01,
[0.53,
[0.02,
[0.30,
[0.37,
7.72]
1.61]
2.26]
0.94]
3.17]
1.07]
1/30
30
3.47
3.47
0.32 [0.01, 7.63]
0.32 [0.01, 7.63]
9/76
76
19.97
19.97
0.82 [0.32, 2.09]
0.82 [0.32, 2.09]
736
769
Total (95% CI)
Total events: 27 (Aspirin adjuvant), 43 (Control)
Test for heterogeneity: Chi² = 7.42, df = 6 (P = 0.28), I² = 19.2%
Test for overall effect: Z = 1.82 (P = 0.07)
100.00
0.66 [0.42, 1.03]
03 Aspirin + IPC+ GCS v IPC + GCS
7/72
WOOLSON1991
72
Subtotal (95% CI)
Total events: 7 (Aspirin adjuvant), 9 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.41 (P = 0.68)
0.01
2
3
RR (fixed)
95% CI
0.1
Favours aspirin
1
10
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
611 of 648
DRAFT FOR CONSULTATION
1
Figure 158. Aspirin adjuvant – major bleed
Review:
VTE Aspirin
Comparison:03 Aspirin adjuvant
Outcome: 04 Major bleed
Study
or sub-category
Aspirin adjuvant
n/N
Control
n/N
RR (fixed)
95% CI
Weight
%
01 Aspirin + unfractionated heparin v unfractionated heparin
1/20
0/20
FLICOTEAUX1977
0/62
0/62
LOEW1977
58/151
47/154
MONREAL1995
11/402
3/404
VINAZZER1980
4/50
1/49
ZEKERT1980
685
689
Subtotal (95% CI)
Total events: 74 (Aspirin adjuvant), 51 (Control)
Test for heterogeneity: Chi² = 3.96, df = 3 (P = 0.27), I² = 24.2%
Test for overall effect: Z = 2.52 (P = 0.01)
02 Aspirin + dipyridamole v dipyridamole
0/31
PARODI1973 iv
0
Subtotal (95% CI)
Total events: 0 (Aspirin adjuvant), 0 (Control)
Test for heterogeneity: not applicable
Test for overall effect: not applicable
0.17
15.40
0.99
0.33
16.89
3.00 [0.13, 69.52]
Not estimable
1.26 [0.92, 1.72]
3.68 [1.04, 13.11]
3.92 [0.45, 33.84]
1.47 [1.09, 1.99]
0/30
0
Not estimable
Not estimable
03 Aspirin adjuvant (variety of additional prophylaxis)
64/2047
75/2041
PEP2000 elective
211/6679
176/6677
PEP2000 hip fracture
8726
8718
Subtotal (95% CI)
Total events: 275 (Aspirin adjuvant), 251 (Control)
Test for heterogeneity: Chi² = 3.08, df = 1 (P = 0.08), I² = 67.5%
Test for overall effect: Z = 1.05 (P = 0.29)
9442
9437
Total (95% CI)
Total events: 349 (Aspirin adjuvant), 302 (Control)
Test for heterogeneity: Chi² = 8.56, df = 5 (P = 0.13), I² = 41.6%
Test for overall effect: Z = 1.95 (P = 0.05)
0.01
2
3
4
RR (fixed)
95% CI
0.1
Favours aspirin
1
10
24.86
58.25
83.11
0.85 [0.61, 1.18]
1.20 [0.98, 1.46]
1.09 [0.92, 1.30]
100.00
1.16 [1.00, 1.34]
100
Favours control
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
612 of 648
DRAFT FOR CONSULTATION
1
Higher dose aspirin vs lower dose aspirin
2
Figure 159. Higher dose aspirin vs lower dose aspirin - DVT
Review:
VTE Aspirin
Comparison:05 Aspirin - higher dose vs lower dose
Outcome: 01 DVT
Study
or sub-category
Treatment
n/N
ALFARO1986
HARRIS1985
MCKENNA1980
Control
n/N
2/30
29/50
1/13
RR (fixed)
95% CI
Weight
%
2.89
75.18
21.93
1/30
26/50
7/11
93
91
Total (95% CI)
Total events: 32 (Treatment), 34 (Control)
Test for heterogeneity: Chi² = 5.74, df = 2 (P = 0.06), I² = 65.2%
Test for overall effect: Z = 0.45 (P = 0.65)
0.01
3
4
100.00
0.1
1
Favours treatment
10
RR (fixed)
95% CI
2.00 [0.19, 20.90]
1.12 [0.78, 1.59]
0.12 [0.02, 0.84]
0.92 [0.65, 1.30]
100
Favours control
Figure 160. Higher dose aspirin vs lower dose aspirin – major bleed
Review:
VTE Aspirin
Comparison:05 Aspirin - higher dose vs lower dose
Outcome: 04 Major bleed
Study
or sub-category
Treatment
n/N
ALFARO1986
MCKENNA1980
Control
n/N
0/30
0/13
43
Total (95% CI)
Total events: 0 (Treatment), 1 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.79 (P = 0.43)
RR (fixed)
95% CI
RR (fixed)
95% CI
0/30
1/11
100.00
Not estimable
0.29 [0.01, 6.38]
41
100.00
0.29 [0.01, 6.38]
0.01
5
Weight
%
0.1
1
Favours treatment
10
100
Favours control
6
7
Aspirin vs unfractionated heparin
8
Figure 161. Aspirin vs unfractionated heparin - DVT
Review:
VTE Aspirin
Comparison:04 Aspirin vs UFH
Outcome: 01 DVT
Study
or sub-category
DECHAVANNE1975
JOSEFSSON1987
LOEW1977
PLANTE1979
ZANASI1988
Aspirin
n/N
10/20
3/40
19/63
3/38
7/19
Unfractionated Hep
n/N
RR (fixed)
95% CI
Weight
%
3.71
10.85
42.84
10.57
32.03
1/20
3/42
11/57
3/42
10/25
180
186
Total (95% CI)
Total events: 42 (Aspirin), 28 (Unfractionated Hep)
Test for heterogeneity: Chi² = 5.77, df = 4 (P = 0.22), I² = 30.7%
Test for overall effect: Z = 2.05 (P = 0.04)
100.00
0.01
9
0.1
Favours aspirin
1
10
RR (fixed)
95% CI
10.00
1.05
1.56
1.11
0.92
[1.41,
[0.22,
[0.82,
[0.24,
[0.43,
70.99]
4.90]
2.99]
5.15]
1.97]
1.57 [1.02, 2.40]
100
Favours heparin
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
613 of 648
DRAFT FOR CONSULTATION
1
2
3
Figure 162. Aspirin vs unfractionated heparin – pulmonary embolism
Review:
VTE Aspirin
Comparison: 04 Aspirin vs UFH
Outcome: 02 Pulmonary embolism
Study
or sub-category
Aspirin
n/N
JOSEFSSON1987
VINAZZER1980
Heparin
n/N
4/40
1/365
RR (fixed)
95% CI
Weight
%
3/42
1/378
74.87
25.13
405
420
Total (95% CI)
Total events: 5 (Aspirin), 4 (Heparin)
Test for heterogeneity: Chi² = 0.04, df = 1 (P = 0.85), I² = 0%
Test for overall effect: Z = 0.41 (P = 0.68)
100.00
0.01
4
5
6
0.1
1
Favours aspirin
10
RR (fixed)
95% CI
1.40 [0.33, 5.87]
1.04 [0.07, 16.50]
1.31 [0.37, 4.66]
100
Favours heparin
Figure 163. Aspirin vs unfractionated heparin – proximal DVT
Review:
VTE Aspirin
Comparison:04 Aspirin vs UFH
Outcome: 03 Proximal DVT
Study
or sub-category
Treatment
n/N
VINAZZER1980
Control
n/N
14/365
365
Total (95% CI)
Total events: 14 (Treatment), 9 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.13 (P = 0.26)
OR (fixed)
95% CI
11
OR (fixed)
95% CI
9/378
100.00
1.64 [0.70, 3.83]
378
100.00
1.64 [0.70, 3.83]
0.01
7
8
9
10
Weight
%
0.1
1
Favours treatment
10
100
Favours control
Figure 164. Aspirin vs unfractionated heparin – major bleed
Review:
VTE Aspirin
Comparison: 04 Aspirin vs UFH
Outcome: 04 Major bleed
Study
or sub-category
JOSEFSSON1987
LOEW1977
VINAZZER1980
Aspirin
n/N
0/40
0/63
3/404
507
Total (95% CI)
Total events: 3 (Aspirin), 3 (Heparin)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.00 (P = 1.00)
Heparin
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
0/42
0/57
3/404
100.00
Not estimable
Not estimable
1.00 [0.20, 4.93]
503
100.00
1.00 [0.20, 4.93]
0.01
12
13
14
15
Weight
%
0.1
Favours aspirin
1
10
100
Favours heparin
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
614 of 648
DRAFT FOR CONSULTATION
1
Mechanical vs pharmacological prophylaxis
2
3
Mechanical compression vs pharmacological prophylaxis –
subgrouped by pharmacological
4
Figure 165. Mechanical compression vs pharmacological – subgrouped
5
by pharmacological - DVT
Review:
Comparison:
Outcome:
Study
or sub-category
VTE Mechanical v pharmacological
01 Mechanical vs pharmacological - subgrouped by pharmacological
01 DVT
Mechanical
n/N
Pharmacological
n/N
RR (random)
95% CI
Weight
%
01 Any mechanical vs unfractionated heparin
3/101
6/107
CLARKEPEARSON1993
1/29
6/28
COE1978
3/52
3/45
FASTING1985
8/49
2/25
HANSBERRY1991
1/68
1/68
KOSIR1998
10/54
2/52
MELLBRING1986
22/74
25/85
RASMUSSEN1998
9/67
23/65
SANTORI1994
494
475
Subtotal (95% CI)
Total events: 57 (Mechanical), 68 (Pharmacological)
Test for heterogeneity: Chi² = 15.39, df = 7 (P = 0.03), I² = 54.5%
Test for overall effect: Z = 0.52 (P = 0.60)
02 Any mechanical vs low molecular weight heparin
34/63
16/67
BLANCHARD1999A
1/106
2/105
MAXWELL2001
4/15
0/14
NOGREN1998
24/136
18/138
WARWICK1998
57/99
48/89
WARWICK2002
419
413
Subtotal (95% CI)
Total events: 120 (Mechanical), 84 (Pharmacological)
Test for heterogeneity: Chi² = 10.04, df = 4 (P = 0.04), I² = 60.2%
Test for overall effect: Z = 1.56 (P = 0.12)
03 Any mechanical vs oral anticoagulant
3/50
12/45
BAILEY1991
4/47
0/53
CHANDHOKE1992
26/98
32/103
FRANCIS1992
12/48
13/52
KAEMPFFE1991
11/66
12/72
PAIEMENT1987
0/35
0/33
ROKITO1996
344
358
Subtotal (95% CI)
Total events: 56 (Mechanical), 69 (Pharmacological)
Test for heterogeneity: Chi² = 7.93, df = 4 (P = 0.09), I² = 49.6%
Test for overall effect: Z = 0.69 (P = 0.49)
04 Any mechanical vs aspirin
8/36
HAAS1990 i
12/25
HAAS1990 ii
1/10
MCKENNA1980
71
Subtotal (95% CI)
Total events: 21 (Mechanical), 40 (Pharmacological)
Test for heterogeneity: Chi² = 1.77, df = 2 (P = 0.41), I² = 0%
Test for overall effect: Z = 2.57 (P = 0.01)
05 Any mechanical vs dextrans
36/95
SMITH1978
95
Subtotal (95% CI)
Total events: 36 (Mechanical), 21 (Pharmacological)
Test for heterogeneity: not applicable
Test for overall effect: Z = 2.40 (P = 0.02)
06 Foot pump vs UF heparin + aspirin
0/25
STANNARD1996
25
Subtotal (95% CI)
Total events: 0 (Mechanical), 5 (Pharmacological)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.65 (P = 0.10)
2.89
1.51
2.38
2.57
0.90
2.58
7.59
6.08
26.51
0.53
0.16
0.87
2.04
1.00
4.81
1.01
0.38
0.85
[0.14,
[0.02,
[0.18,
[0.47,
[0.06,
[1.11,
[0.62,
[0.19,
[0.45,
2.06]
1.25]
4.08]
8.90]
15.66]
20.93]
1.63]
0.76]
1.59]
7.57
1.17
0.86
6.99
9.12
25.69
2.26
0.50
8.44
1.35
1.07
1.45
[1.39,
[0.05,
[0.50,
[0.77,
[0.83,
[0.91,
3.67]
5.38]
143.77]
2.38]
1.38]
2.33]
3.42
0.82
7.91
6.16
5.71
24.03
0.23 [0.07, 0.75]
10.13 [0.56, 183.23]
0.85 [0.55, 1.32]
1.00 [0.51, 1.97]
1.00 [0.47, 2.11]
Not estimable
0.83 [0.49, 1.41]
17/36
15/22
8/21
79
6.01
7.47
1.67
15.14
21/97
97
7.76
7.76
1.75 [1.11, 2.77]
1.75 [1.11, 2.77]
5/25
25
0.85
0.85
0.09 [0.01, 1.56]
0.09 [0.01, 1.56]
100.00
0.94 [0.71, 1.23]
1448
1447
Total (95% CI)
Total events: 290 (Mechanical), 287 (Pharmacological)
Test for heterogeneity: Chi² = 56.96, df = 22 (P < 0.0001), I² = 61.4%
Test for overall effect: Z = 0.47 (P = 0.64)
0.01
6
7
RR (random)
95% CI
0.1
Favours mechanical
1
10
0.47
0.70
0.26
0.59
[0.23,
[0.43,
[0.04,
[0.40,
0.95]
1.16]
1.82]
0.88]
100
Favours pharmalogica
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
615 of 648
DRAFT FOR CONSULTATION
1
Figure 166. Mechanical compression vs pharmacological – subgrouped
2
by pharmacological – pulmonary embolism
Review:
Comparison:
Outcome:
VTE Mechanical v pharmacological
01 Mechanical vs pharmacological - subgrouped by pharmacological
02 Pulmonary embolism
Study
or sub-category
Mechanical
n/N
Pharmacological
n/N
01 Any mechanical vs unfractionated heparin
1/29
COE1978
2/49
HANSBERRY1991
1/68
KOSIR1998
146
Subtotal (95% CI)
Total events: 4 (Mechanical), 3 (Pharmacological)
Test for heterogeneity: Chi² = 0.00, df = 2 (P = 1.00), I² = 0%
Test for overall effect: Z = 0.00 (P = 1.00)
02 Any mechanical vs low molecular weight heparin
0/63
BLANCHARD1999A
1/136
WARWICK1998
199
Subtotal (95% CI)
Total events: 1 (Mechanical), 0 (Pharmacological)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.68 (P = 0.49)
03 Any mechanical vs oral anticoagulant
2/47
CHANDHOKE1992
0/66
PAIEMENT1987
0/35
ROKITO1996
148
Subtotal (95% CI)
Total events: 2 (Mechanical), 0 (Pharmacological)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.12 (P = 0.26)
04 Any mechanical vs aspirin
2/36
HAAS1990 i
1/25
HAAS1990 ii
1/10
MCKENNA1980
71
Subtotal (95% CI)
Total events: 4 (Mechanical), 4 (Pharmacological)
Test for heterogeneity: Chi² = 0.65, df = 2 (P = 0.72), I² = 0%
Test for overall effect: Z = 0.46 (P = 0.65)
564
Total (95% CI)
Total events: 11 (Mechanical), 7 (Pharmacological)
Test for heterogeneity: Chi² = 1.91, df = 7 (P = 0.96), I² = 0%
Test for overall effect: Z = 1.01 (P = 0.31)
RR (fixed)
95% CI
1/28
1/25
1/68
121
13.09
17.03
12.86
42.98
0/67
0/138
205
6.38
6.38
0/53
0/72
0/33
158
6.05
6.05
1/36
0/22
3/21
79
12.86
6.82
24.89
44.58
563
100.00
0.01
3
4
Weight
%
0.1
Favours mechanical
1
10
RR (fixed)
95% CI
0.97
1.02
1.00
1.00
[0.06,
[0.10,
[0.06,
[0.22,
14.70]
10.72]
15.66]
4.45]
Not estimable
3.04 [0.13, 74.07]
3.04 [0.13, 74.07]
5.63 [0.28, 114.27]
Not estimable
Not estimable
5.63 [0.28, 114.27]
2.00
2.65
0.70
1.37
[0.19,
[0.11,
[0.08,
[0.35,
21.09]
62.00]
5.92]
5.35]
1.58 [0.65, 3.81]
100
Favours pharmalogica
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
616 of 648
DRAFT FOR CONSULTATION
1
Figure 167. Mechanical compression vs pharmacological – subgrouped
2
by pharmacological – proximal DVT
Review:
VTE Mechanical v pharmacological
Comparison: 01 Mechanical vs pharmacological - subgrouped by pharmacological
Outcome:
03 Proximal DVT
Study
or sub-category
Mechanical
n/N
Pharmacological
n/N
01 Any mechanical vs unfractionated heparin
0/101
CLARKEPEARSON1993
0/15
KILLEWICH2002
116
Subtotal (95% CI)
Total events: 0 (Mechanical), 2 (Pharmacological)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.01 (P = 0.31)
RR (fixed)
95% CI
Weight
%
2/107
0/16
123
6.99
6.99
02 Any mechanical vs low molecular weight heparin
4/63
2/67
BLANCHARD1999A
1/106
2/105
MAXWELL2001
17/136
12/138
WARWICK1998
4/99
0/89
WARWICK2002
404
399
Subtotal (95% CI)
Total events: 26 (Mechanical), 16 (Pharmacological)
Test for heterogeneity: Chi² = 2.34, df = 3 (P = 0.51), I² = 0%
Test for overall effect: Z = 1.59 (P = 0.11)
03 Any mechanical vs oral anticoagulant
12/98
3/103
FRANCIS1992
8/48
6/52
KAEMPFFE1991
9/66
4/72
PAIEMENT1987
212
227
Subtotal (95% CI)
Total events: 29 (Mechanical), 13 (Pharmacological)
Test for heterogeneity: Chi² = 1.82, df = 2 (P = 0.40), I² = 0%
Test for overall effect: Z = 2.74 (P = 0.006)
04 Any mechanical vs aspirin
0/36
0/36
HAAS1990 i
2/25
1/22
HAAS1990 ii
0/10
3/21
MCKENNA1980
71
79
Subtotal (95% CI)
Total events: 2 (Mechanical), 4 (Pharmacological)
Test for heterogeneity: Chi² = 0.95, df = 1 (P = 0.33), I² = 0%
Test for overall effect: Z = 0.34 (P = 0.73)
803
Total (95% CI)
Total events: 57 (Mechanical), 35 (Pharmacological)
Test for heterogeneity: Chi² = 8.31, df = 9 (P = 0.50), I² = 0%
Test for overall effect: Z = 2.63 (P = 0.009)
2.13
0.50
1.44
8.10
1.62
[0.40,
[0.05,
[0.71,
[0.44,
[0.89,
11.21]
5.38]
2.89]
148.37]
2.92]
8.42
16.59
11.02
36.03
4.20
1.44
2.45
2.40
[1.22,
[0.54,
[0.79,
[1.28,
14.45]
3.86]
7.59]
4.48]
100.00
0.01
3
4
0.1
Favours mechanical
1
10
0.21 [0.01, 4.36]
Not estimable
0.21 [0.01, 4.36]
5.58
5.79
34.31
1.52
47.19
3.06
6.72
9.78
828
RR (fixed)
95% CI
Not estimable
1.76 [0.17, 18.11]
0.29 [0.02, 5.06]
0.75 [0.14, 3.92]
1.72 [1.15, 2.56]
100
Favours pharmalogica
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
617 of 648
DRAFT FOR CONSULTATION
1
Figure 168. Mechanical compression vs pharmacological – subgrouped
2
by pharmacological – major bleed
Review:
VTE Mechanical v pharmacological
Comparison: 01 Mechanical vs pharmacological - subgrouped by pharmacological
Outcome:
04 Major bleeds
Study
or sub-category
Mechanical
n/N
Pharmacological
n/N
01 Any mechanical vs unfractionated heparin
0/52
FASTING1985
0
Subtotal (95% CI)
Total events: 0 (Mechanical), 0 (Pharmacological)
Test for heterogeneity: not applicable
Test for overall effect: not applicable
02 Any mechanical vs low molecular weight heparin
0/63
BLANCHARD1999A
63
Subtotal (95% CI)
Total events: 0 (Mechanical), 1 (Pharmacological)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.64 (P = 0.52)
03 Any mechanical vs oral anticoagulant
0/50
BAILEY1991
0/66
PAIEMENT1987
0
Subtotal (95% CI)
Total events: 0 (Mechanical), 0 (Pharmacological)
Test for heterogeneity: not applicable
Test for overall effect: not applicable
04 Any mechanical vs aspirin
0/10
MCKENNA1980
10
Subtotal (95% CI)
Total events: 0 (Mechanical), 1 (Pharmacological)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.25 (P = 0.80)
RR (fixed)
95% CI
0/45
0
RR (fixed)
95% CI
Not estimable
Not estimable
59.26
59.26
1/67
67
0/45
0/72
0
0.35 [0.01, 8.54]
0.35 [0.01, 8.54]
Not estimable
Not estimable
Not estimable
1/21
21
40.74
40.74
241
250
Total (95% CI)
Total events: 0 (Mechanical), 2 (Pharmacological)
Test for heterogeneity: Chi² = 0.08, df = 1 (P = 0.78), I² = 0%
Test for overall effect: Z = 0.65 (P = 0.52)
100.00
0.01
3
Weight
%
0.1
Favours mechanical
1
10
0.67 [0.03, 15.06]
0.67 [0.03, 15.06]
0.48 [0.05, 4.36]
100
Favours pharmalogica
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
618 of 648
DRAFT FOR CONSULTATION
1
2
Electrical stimulation vs pharmacological prophylaxis –
subgrouped by pharmacological
3
Figure 169. Electrical stimulation vs pharmacological – subgrouped by
4
pharmacological - DVT
Review:
VTE Mechanical v pharmacological
Comparison: 02 Electrical stimulation (ES) vs pharmacological - subgrouped by pharmacological
Outcome:
01 DVT
Study
or sub-category
ES
n/N
01 Dextran
5/37
LINDSTROM1982
37
Subtotal (95% CI)
Total events: 5 (ES), 7 (Pharmacological)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.73 (P = 0.46)
02 UFH
12/50
NICCOLAIDES1983
50
Subtotal (95% CI)
Total events: 12 (ES), 7 (Pharmacological)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.25 (P = 0.21)
Pharmacological
n/N
RR (fixed)
95% CI
Weight
%
RR (fixed)
95% CI
7/35
35
50.68
50.68
0.68 [0.24, 1.93]
0.68 [0.24, 1.93]
7/50
50
49.32
49.32
1.71 [0.74, 3.99]
1.71 [0.74, 3.99]
100.00
1.19 [0.63, 2.26]
87
85
Total (95% CI)
Total events: 17 (ES), 14 (Pharmacological)
Test for heterogeneity: Chi² = 1.83, df = 1 (P = 0.18), I² = 45.4%
Test for overall effect: Z = 0.53 (P = 0.60)
0.01
5
6
0.1
1
Favours ES
10
100
Favours pharmacol
7
Figure 170. Electrical stimulation vs pharmacological – subgrouped by
8
pharmacological – pulmonary embolism
Review:
VTE Mechanical v pharmacological
Comparison: 02 Electrical stimulation (ES) vs pharmacological - subgrouped by pharmacological
Outcome:
02 Pulmonary embolism
Study
or sub-category
ES
n/N
01 Dextran
6/37
LINDSTROM1982
37
Subtotal (95% CI)
Total events: 6 (ES), 4 (Pharmacological)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.58 (P = 0.56)
37
Total (95% CI)
Total events: 6 (ES), 4 (Pharmacological)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.58 (P = 0.56)
Pharmacological
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
4/35
35
100.00
100.00
1.42 [0.44, 4.61]
1.42 [0.44, 4.61]
35
100.00
1.42 [0.44, 4.61]
0.01
9
10
Weight
%
0.1
Favours ES
1
10
100
Favours pharmacol
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
619 of 648
DRAFT FOR CONSULTATION
1
Figure 171. Electrical stimulation vs pharmacological – subgrouped by
2
pharmacological – proximal DVT
Review:
VTE Mechanical v pharmacological
Comparison:02 Electrical stimulation (ES) vs pharmacological - subgrouped by pharmacological
Outcome: 03 Proximal DVT
Study
or sub-category
ES
n/N
01 UFH
2/50
NICCOLAIDES1983
50
Subtotal (95% CI)
Total events: 2 (ES), 1 (Pharmacological)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.57 (P = 0.57)
50
Total (95% CI)
Total events: 2 (ES), 1 (Pharmacological)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.57 (P = 0.57)
Pharmacological
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
1/50
50
100.00
100.00
2.00 [0.19, 21.36]
2.00 [0.19, 21.36]
50
100.00
2.00 [0.19, 21.36]
0.01
3
Weight
%
0.1
Favours ES
1
10
100
Favours pharmacol
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
620 of 648
DRAFT FOR CONSULTATION
1
Anaesthesia
2
Regional vs general anaesthesia
3
Figure 172. Regional vs general anaesthesia - DVT
Review:
VTE Anaesthesia
Comparison: 01 Regional vs general
Outcome:
01 DVT
Study
or sub-category
BRICHANT1995
DAVIS1981
DAVIS1989
FREDIN1986
HENDOLIN1981
HENDOLIN1982
JORGENSEN1991
MCKENZIE1985
MITCHELL1991
MODIG1981
MODIG1985
NIELSEN1990
POIKOLAINEN1983
RODRIGO1984
WILLIAMSRUSSO1996
Regional
n/N
General
n/N
RR (random)
95% CI
13/42
28/39
19/68
12/25
11/20
2/40
13/22
16/20
10/38
11/15
38/48
10/16
11/21
7/11
39/81
7.61
12.56
6.32
7.98
2.21
0.79
3.29
8.45
6.56
5.62
13.99
2.30
2.20
5.53
14.60
496
506
Total (95% CI)
Total events: 151 (Regional), 240 (General)
Test for heterogeneity: Chi² = 21.21, df = 14 (P = 0.10), I² = 34.0%
Test for overall effect: Z = 4.33 (P < 0.0001)
100.00
14/46
17/37
9/69
11/26
2/17
1/28
3/17
8/20
12/34
5/15
21/48
2/13
2/17
5/11
39/98
0.01
4
5
Weight
%
0.1
1
Favours regional
10
RR (random)
95% CI
0.98
0.64
0.47
0.88
0.21
0.71
0.30
0.50
1.34
0.45
0.55
0.25
0.22
0.71
0.83
[0.52,
[0.43,
[0.23,
[0.48,
[0.05,
[0.07,
[0.10,
[0.28,
[0.67,
[0.21,
[0.39,
[0.07,
[0.06,
[0.33,
[0.59,
1.84]
0.96]
0.96]
1.62]
0.83]
7.50]
0.88]
0.89]
2.70]
0.99]
0.79]
0.93]
0.88]
1.57]
1.15]
0.62 [0.51, 0.77]
100
Favours general
Figure 173. Regional vs general anaesthesia – Pulmonary embolism
Review:
VTE Anaesthesia
Comparison: 01 Regional vs general
Outcome:
02 Pulmonary embolism
Study
or sub-category
Weight
%
RR (fixed)
95% CI
3/68
7/30
1/24
7/15
15/50
0/11
6/81
8.69
17.26
3.70
17.26
36.98
16.12
0.14 [0.01, 2.68]
0.86 [0.33, 2.25]
0.33 [0.01, 7.80]
0.29 [0.07, 1.16]
0.33 [0.13, 0.85]
Not estimable
1.39 [0.53, 3.66]
296
279
Total (95% CI)
Total events: 23 (Regional), 39 (General)
Test for heterogeneity: Chi² = 7.14, df = 5 (P = 0.21), I² = 29.9%
Test for overall effect: Z = 2.33 (P = 0.02)
100.00
0.57 [0.35, 0.91]
DAVIS1989
FREDIN1986
JORGENSEN1991
MODIG1981
MODIG1985
RODRIGO1984
WILLIAMSRUSSO1996
Regional
n/N
0/69
6/30
0/24
2/15
5/50
0/11
10/97
General
n/N
RR (fixed)
95% CI
0.01
6
0.1
Favours regional
1
10
100
Favours general
Venous thromboembolism: full guideline appendices DRAFT (October 2006)
621 of 648
DRAFT FOR CONSULTATION
1
Figure 174. Regional vs general anaesthesia – Proximal DVT
Review:
VTE Anaesthesia
Comparison: 01 Regional vs general
Outcome:
03 Proximal DVT
Study
or sub-category
DAVIS1989
FREDIN1986
JORGENSEN1991
MODIG1981
MODIG1985
NIELSEN1990
RODRIGO1984
WILLIAMSRUSSO1996
Regional
n/N
3/69
1/26
1/17
3/15
8/48
1/13
1/11
0/97
General
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
13.20
3.34
4.28
18.02
50.19
4.41
6.55
0.37 [0.10, 1.33]
0.48 [0.05, 4.98]
0.43 [0.05, 3.79]
0.27 [0.09, 0.78]
0.26 [0.13, 0.50]
0.41 [0.05, 3.49]
0.25 [0.03, 1.90]
Not estimable
100.00
0.30 [0.19, 0.47]
8/68
2/25
3/22
11/15
30/46
3/16
4/11
0/81
296
Total (95% CI)
Total events: 18 (Regional), 61 (General)
Test for heterogeneity: Chi² = 0.72, df = 6 (P = 0.99), I² = 0%
Test for overall effect: Z = 5.14 (P < 0.00001)
284
0.01
2
3
Weight
%
0.1
1
Favours regional
10
100
Favours general
Figure 175. Regional vs general anaesthesia – Major Bleed
Review:
VTE Anaesthesia
Comparison: 01 Regional vs general
Outcome:
04 Major bleed
Study
or sub-category
BRICHANT1995
DAVIS1981
FREDIN1986
HENDOLIN1982
JORGENSEN1991
MCKENZIE1985
WILLIAMSRUSSO1996
Regional
n/N
General
n/N
0/54
0/64
0/30
0/28
0/24
0/20
0/97
0/52
5/68
0/30
0/40
0/24
0/20
0/81
317
Total (95% CI)
Total events: 0 (Regional), 5 (General)
Test for heterogeneity: not applicable
Test for overall effect: Z = 1.59 (P = 0.11)
315
RR (fixed)
95% CI
100.00
100.00
0.01
4
5
Weight
%
0.1
Favours regional
1
10
RR (fixed)
95% CI
Not estimable
0.10 [0.01, 1.71]
Not estimable
Not estimable
Not estimable
Not estimable
Not estimable
0.10 [0.01, 1.71]
100
Favours general
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1
2
Regional vs general anaesthesia subgrouped by spinal and
epidural
3
Figure 176. Regional vs general anaesthesia subgrouped by spinal and
4
epidural –DVT
Review:
VTE Anaesthesia
Comparison: 03 Regional vs general - subgrouped by spinal or epidural
Outcome:
01 DVT
Study
or sub-category
Regional
n/N
General
n/N
RR (fixed)
95% CI
Weight
%
01 Epidural v general
11/26
12/25
FREDIN1986
2/17
11/20
HENDOLIN1981
1/28
2/40
HENDOLIN1982
3/17
13/22
JORGENSEN1991
12/34
10/38
MITCHELL1991
5/15
11/15
MODIG1981
21/48
38/48
MODIG1985
2/13
10/16
NIELSEN1990
2/17
11/21
POIKOLAINEN1983
5/11
7/11
RODRIGO1984
39/98
39/81
WILLIAMSRUSSO1996
324
337
Subtotal (95% CI)
Total events: 103 (Regional), 164 (General)
Test for heterogeneity: Chi² = 18.03, df = 10 (P = 0.05), I² = 44.6%
Test for overall effect: Z = 4.87 (P < 0.00001)
02 spinal v general
14/46
13/42
BRICHANT1995
17/37
28/39
DAVIS1981
9/69
19/68
DAVIS1989
8/20
16/20
MCKENZIE1985
172
169
Subtotal (95% CI)
Total events: 48 (Regional), 76 (General)
Test for heterogeneity: Chi² = 3.21, df = 3 (P = 0.36), I² = 6.6%
Test for overall effect: Z = 3.28 (P = 0.001)
496
506
Total (95% CI)
Total events: 151 (Regional), 240 (General)
Test for heterogeneity: Chi² = 21.21, df = 14 (P = 0.10), I² = 34.0%
Test for overall effect: Z = 5.87 (P < 0.00001)
0.01
5
5.14
4.24
0.69
4.76
3.96
4.62
15.95
3.76
4.13
2.94
17.92
68.11
0.88
0.21
0.71
0.30
1.34
0.45
0.55
0.25
0.22
0.71
0.83
0.62
[0.48,
[0.05,
[0.07,
[0.10,
[0.67,
[0.21,
[0.39,
[0.07,
[0.06,
[0.33,
[0.59,
[0.51,
1.62]
0.83]
7.50]
0.88]
2.70]
0.99]
0.79]
0.93]
0.88]
1.57]
1.15]
0.75]
5.70
11.44
8.03
6.72
31.89
0.98
0.64
0.47
0.50
0.63
[0.52,
[0.43,
[0.23,
[0.28,
[0.48,
1.84]
0.96]
0.96]
0.89]
0.83]
100.00
0.1
Favours regional
1
10
RR (fixed)
95% CI
0.62 [0.53, 0.73]
100
Favours general
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Figure 177. Regional vs general anaesthesia subgrouped by spinal and
2
epidural – Pulmonary embolism
Review:
VTE Anaesthesia
Comparison: 03 Regional vs general - subgrouped by spinal or epidural
Outcome:
02 Pulmonary embolism
Study
or sub-category
Regional
n/N
General
n/N
RR (fixed)
95% CI
Weight
%
RR (fixed)
95% CI
12.46
2.67
12.46
26.70
11.64
65.93
0.86 [0.33, 2.25]
0.33 [0.01, 7.80]
0.29 [0.07, 1.16]
0.33 [0.13, 0.85]
Not estimable
1.39 [0.53, 3.66]
0.61 [0.38, 0.99]
19/68
68
34.07
34.07
0.47 [0.23, 0.96]
0.47 [0.23, 0.96]
296
279
Total (95% CI)
Total events: 32 (Regional), 55 (General)
Test for heterogeneity: Chi² = 6.57, df = 5 (P = 0.25), I² = 23.9%
Test for overall effect: Z = 2.83 (P = 0.005)
100.00
0.56 [0.38, 0.84]
01 Epidural v general
6/30
7/30
FREDIN1986
0/24
1/24
JORGENSEN1991
2/15
7/15
MODIG1981
5/50
15/50
MODIG1985
0/11
0/11
RODRIGO1984
10/97
6/81
WILLIAMSRUSSO1996
227
211
Subtotal (95% CI)
Total events: 23 (Regional), 36 (General)
Test for heterogeneity: Chi² = 6.15, df = 4 (P = 0.19), I² = 34.9%
Test for overall effect: Z = 2.01 (P = 0.04)
02 Spinal v general
9/69
DAVIS1989
69
Subtotal (95% CI)
Total events: 9 (Regional), 19 (General)
Test for heterogeneity: not applicable
Test for overall effect: Z = 2.08 (P = 0.04)
0.01
3
4
5
0.1
1
Favours regional
10
100
Favours general
6
Regional + general vs general anaesthesia
7
Figure 178. Regional + general vs general anaesthesia - DVT
Review:
VTE Anaesthesia
Comparison:02 Regional + general vs general
Outcome: 01 DVT
Study
or sub-category
DAUPHIN1997
HENDOLIN1982
Regional
n/N
4/20
2/30
General
n/N
RR (fixed)
95% CI
Weight
%
4/17
5/40
50
57
Total (95% CI)
Total events: 6 (Regional), 9 (General)
Test for heterogeneity: Chi² = 0.21, df = 1 (P = 0.64), I² = 0%
Test for overall effect: Z = 0.74 (P = 0.46)
0.01
8
9
0.1
Favours regional
1
10
RR (fixed)
95% CI
50.22
49.78
0.85 [0.25, 2.90]
0.53 [0.11, 2.56]
100.00
0.69 [0.26, 1.82]
100
Favours general
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Other prophylaxis
2
Foot elevation
3
Figure 179. Foot elevation vs no foot elevation - DVT
Review:
VTE Other prophylaxis
Comparison:02 Foot elevation vs no foot elevation
Outcome: 01 DVT
Study
or sub-category
ROSENGARTEN1971A
Foot elevation
n/N
No foot elevation
n/N
4/12
12
Total (95% CI)
Total events: 4 (Foot elevation), 4 (No foot elevation)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.14 (P = 0.89)
Weight
%
RR (fixed)
95% CI
4/13
100.00
1.08 [0.35, 3.40]
13
100.00
1.08 [0.35, 3.40]
0.01
4
5
RR (fixed)
95% CI
0.1
1
Favours elevation
10
100
Favours no elevation
Figure 180. Foot elevation vs no foot elevation – Proximal DVT
Review:
VTE Other prophylaxis
Comparison: 02 Foot elevation vs no foot elevation
Outcome: 02 Proximal DVT
Study
or sub-category
ROSENGARTEN1971A
Foot elevation
n/N
No foot elevation
n/N
1/12
12
Total (95% CI)
Total events: 1 (Foot elevation), 1 (No foot elevation)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.06 (P = 0.95)
RR (fixed)
95% CI
Weight
%
RR (fixed)
95% CI
1/13
100.00
1.08 [0.08, 15.46]
13
100.00
1.08 [0.08, 15.46]
0.01
6
0.1
1
Favours elevation
7
Hydration
8
Figure 181. IV saline vs no IV saline - DVT
10
100
Favours no elevation
Review:
VTE Other prophylaxis
Comparison:01 Intravenous (IV) saline fluids vs no IV saline
Outcome: 01 DVT
Study
or sub-category
JANVRIN1980
IV saline
n/N
9/30
30
Total (95% CI)
Total events: 9 (IV saline), 2 (No IV saline)
Test for heterogeneity: not applicable
Test for overall effect: Z = 2.04 (P = 0.04)
No IV saline
n/N
RR (fixed)
95% CI
RR (fixed)
95% CI
2/30
100.00
4.50 [1.06, 19.11]
30
100.00
4.50 [1.06, 19.11]
0.01
9
10
11
12
13
Weight
%
0.1
Favours IV saline
1
10
100
Favours no IV saline
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APPENDIX F
2
Mixed Treatment Comparisons Meta-analysis –
3
Methods
4
5
1 Data and assumptions
6
7
8
9
10
To estimate these relative risks we have performed a maximum likelihood
mixed-treatment comparisons (MTC) meta-analysis that simultaneously uses
all the RCT evidence to produce consistent effect sizes for all possible
comparisons335. Data from all the relevant RCTs in our clinical review
(Chapters 5, 6 and 7) were included in the analysis.
11
We produced four MTC models:
12
13
14
1. Single intervention DVT meta-analysis. We took into account single
prophylaxis interventions only. We explicitly excluded combined
strategies.
15
16
17
2. Single/combined DVT meta-analysis. We combined all the
mechanical devices into one category (Mech). We also added in two
combination strategies Mech+UFH and Mech+LMWH .
18
3. Model 2) but adding a strategy of two mechanical devices
19
20
21
22
23
24
4. Major bleeding meta-analysis. Mechanical devices do not influence
major bleeding. Therefore, for this model mechanical only strategies
were re-categorised as “nil”. Likewise combination strategies were
categorised according to their drug component only. We assumed that
the major bleeding rate for mechanical only strategies was the same as
for the nil strategy
25
26
The data used in each model have been summarised by treatment
comparison in Table 1, Table 2 and Table 3.
27
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Table 1: Summary of data included in the Major bleeding MTC model
Comparison
Asp vs Nil
Asp vs UFH
Dan vs LMWH
Dan vs OAC-adj
Fon vs LMWH
LMWH vs Nil
LMWH vs Nil vs UFH
LMWH vs OAC-adj
LMWH vs UFH
Nil vs OAC-adj
Nil vs OAC-adj vs UFH
Nil vs UFH
OAC-adj vs UFH
All
Number of
patients
experiencing
the event
7
6
5
14
242
140
4
333
660
48
8
248
15
1730
Total
number
of
patients
534
808
573
488
10095
6706
356
11261
18558
558
145
4532
285
54899
Number
of
studies
4
1
1
1
2
11
1
10
34
5
1
34
3
108
2
3
4
5
6
Source: 1,5,9,10,14,27,38-
7
8
Source includes one paper that reported three trials445, one paper that reported two trials300,
one paper that reported 4 trials140. adj= adjustable dose
40,44,47,49,50,65,66,71,86,92,98,105,107,108,112,114,125,141,146,156,164,171,175,181,184,192,197,199,204,206,213,219,223,225,226,230
,235,244,247,252,266,270,275,282,294,300302,313,317,319,320,322,324,325,333,341,355,357,374,376,383,384,388,389,393,396,403,406,409,412,413,426,439,441,443445,454,458,465,495,497,504,511,516,519,524,525,542,559,560,563,564,567
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2
Table 2: Summary of data included in the single intervention DVT MTC model
Comparison
Asp vs Dan
Asp vs IPCD
Asp vs IPCD vs Nil
Asp vs Nil
Asp vs Nil vs OAC-adj
Asp vs Nil vs UFH
Asp vs OAC-adj
Asp vs UFH
Dan vs LMWH
Dan vs Nil
Dan vs OAC-adj
Dan vs UFH
Fon vs LMWH
FP vs IPCD
FP vs LMWH
FP vs Nil
GCS vs IPCD vs UFH
GCS vs Nil
GCS vs UFH
IPCD vs LMWH
IPCD vs Nil
IPCD vs Nil vs UFH
IPCD vs OAC-adj
IPCD vs UFH
LMWH vs Nil
LMWH vs Nil vs UFH
LMWH vs OAC-adj
LMWH vs UFH
Nil vs OAC-adj
Nil vs OAC-adj vs UFH
Nil vs UFH
OAC-adj vs UFH
All
Number of
patients
experiencing
the event
63
52
18
687
69
39
206
55
16
71
82
131
639
3
151
45
10
200
6
3
369
12
110
11
322
182
1445
1307
133
17
1092
158
7704
Total
number
of
patients
178
119
43
2330
194
206
418
239
162
196
396
774
7417
117
491
126
74
866
97
211
1897
81
539
344
1564
477
6624
19996
322
145
5831
579
53053
Number
of
studies
1
1
1
20
1
2
2
3
1
1
1
2
5
1
3
2
1
6
1
1
15
1
4
2
14
2
9
48
4
1
44
6
206
3
4
5
6
7
8
9
SOURCE: 1,4,6,8,9,11,13,19,21,24,25,28-30,34,35,38,40,44,47,49,50,56,65,66,68,76,83,84,86,87,92,93,95-103,107,108,112,115,125-
10
11
12
13
Source includes: one paper that reported three trials445; one paper that reported two trials 300;
one paper which includes 4 trials140; one paper which includes 3 trials180; one study which
includes three trials375; one study which includes two trials402 and Antiplatelet Trialists'
Collaboration21 which is the right reference for Anon 1972. adj= adjustable dose
127,139-142,148,152,155,156,162,164,169,171,177-181,184,185,187,192,197-199,204-
206,208,210,211,213,219,223,225,226,229,232,237,241-244,247,250,252,263,264,267,272-275,282,294297,299,300,304,306,310,313,314,317,319-322,325,326,331333,338,341,342,349,352,355,357,360,362,370,374,375,383,387,389,392,393,396,400,402,406,409,410,413,415,425,426,443,445,454456,460,462,463,466,472,476,478,486,491,495,501,504-508,511,512,515,516,518,521,525,533,536,537,540-543,553,555,556,559564,566,567
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2
3
4
5
Table 3: Summary of data included in the single/combination intervention DVT
MTC models
Comparison
Asp vs Dan
Asp vs Mech
Asp vs Mech vs Nil
Asp vs Nil
Asp vs Nil vs OAC-adj
Asp vs Nil vs UFH
Asp vs OAC-adj
Asp vs UFH
Dan vs LMWH
Dan vs Nil
Dan vs OAC-adj
Dan vs UFH
Fon vs LMWH
Fon vs Nil
LMWH vs LMWH+Mech
LMWH vs Mech
LMWH vs Nil
LMWH vs Nil vs UFH
LMWH vs OAC-adj
LMWH vs UFH
LMWH+Mech vs Mech
LMWH+Mech vs UFH+Mech
Mech vs Nil
Mech vs Nil vs UFH
Mech vs OAC-adj
Mech vs UFH
Mech vs UFH vs UFH+Mech
Mech vs UFH+Mech
Nil vs OAC-adj
Nil vs OAC-adj vs UFH
Nil vs UFH
Nil vs UFH+Mech
OAC-adj vs UFH
UFH vs UFH+Mech
All (excl Double Mech)
Number of
patients
experiencing
the event
63
52
18
687
69
39
206
55
16
71
82
131
473
77
9
154
322
182
1445
1307
398
147
622
12
110
17
70
145
176
17
1120
3
135
54
8484
Total
number of
patients
178
119
43
2330
194
206
418
239
162
196
396
774
6170
426
191
702
1564
477
6624
19996
1302
849
3065
81
539
441
248
710
479
145
6073
90
492
602
56521
Number
of
studies
1
1
1
20
1
2
2
3
1
1
1
2
4
1
1
4
14
2
9
48
6
4
24
1
4
3
1
7
6
1
45
1
5
4
231
Sensitivity analysis only
Double Mech vs Mech
Double Mech vs LMWH
Double Mech vs Mech+UFH
50
4
32
568
29
132
6
1
1
All
8570
57250
239
Source: 1,4,6,8-11,13,21,24,25,28-30,34,35,38,40,44,47,49,50,56,65,66,68,76,83,84,86,87,92,93,95-103,107,108,112,114,115,125127,139-141,143,148,152,153,155,156,162,164,169,171,177-181,184,185,187,192,197-199,201,204-
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1
2
3
4
5
6
7
8
9
10
206,210,211,213,219,223,225,226,229,232,237,241-244,247,250,252,263,264,267,272-276,282,289,294-297,299,300,303,304,306,310,312314,317,319-322,324-326,328,331-333,338,341,342,349,352,355,357,360,362,370,374-376,378,383,384,387389,392,393,396,400,402,406,407,409,410,412,413,415,422,425,426,428,443-445,445,454456,458,460,462,463,465,471,472,476,478,486,491,495,497,501,503-508,510-512,515,516,518,519,521,525,533,535-537,540543,548,549,553,555,556,559-564,566,567
Source (double mechanical): 89,160,432,450,461,539. Source includes one paper that reported three
trials445; one paper that reported two trials 300; one paper that reported which includes 4
trials140; one paper that reported 3 trials180; one paper that reported three trials375; one paper
that reported two trials402 and Antiplatelet Trialists' Collaboration21 which is the right reference
for Anon 1972. adj= adjustable dose
11
12
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1
2
2 The model
3
4
5
We used a linear MTC model developed by Lumley335. As Bucher et al. have
shown81, indirect estimates can be combined in large samples if there is
insubstantial interaction between the treatment effects and study populations.
6
7
8
A key component of MTC modelsis that a single effect can potentially be
estimated from a number of different comparisons. For example, LMWH vs Nil
can be estimated by
9
a) trials that estimate directly LMWH vs Nil,
10
b) combining LMWH vs UFH with UFH v Nil
11
c) combining LMWH vs Mech with Mech v Nil
12
d) combining LMWH vs UFH with UFH vs Mech and Mech v Nil
13
etc.
14
15
16
17
18
19
20
In Lumley’s approach, the reliability of treatment effects is assessed by
computing the differences between these various comparisons. A key statistic
is the variance of these differences over and above what would be expected
from sampling error within each trial is described as the “incoherence”. The
incoherence statistic can be used to assess the amount of inconsistency
between studies and is used to adjust confidence intervals to account for this
uncertainty.
21
The following notation is used for the model:
22
Yijk are the log relative risks for the kth randomised trial comparing i to j and
23
its estimated standard error by σ ijk .
24
The model is defined as follows:
25
Yijk ~ N μ i − μ j + ξ ij + ε ijk , σ ijk2
(
)
ε ijk ~ N (0,26
τ 2)
27
ξ ij ~ N (0, ω 2 )
28
where μ i and μ j are the unknown mean effects of treatment i and j .
29
Random effects ε ijk with variance τ 2 represent the difference between the
30
31
average effects of treatments i and j and their effect in the study. They
capture the heterogeneity of treatment effect. The random effect ξ ij represent
32
a change in the effect of treatment i when it is compared to treatment j . The
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1
term ξ ij captures the inconsistency of this pair of treatments with the rest of
2
the evidence.
3
Following Lumley, we call ω 2 = var[ξ ] .
4
5
The heterogeneity is modelled in a flexible manner by specifying the variance
in terms of a linear function of the standard error for the trial:
6
var[Yijk | ε , ξ ] = a (b + σ )
7
8
In this model, a is a dispersion parameter, b is the unknown amount of
heterogeneity at the individual level.
2
9
10
11
Using the example of the single intervention DVT meta-analysis which
includes 11 treatments including the placebo arm, the model can be written
as:
12
Yijk = β1 X 1 + β 2 X 2 + β 3 X 3 + β 4 X 4 + β 5 X 5 + β 6 X 6 + β 7 X 7 + β 8 X 8 + β 9 X 9 + β10 X 10 + ξ ij + ε ijk
13
17
The variables X are defined for each treatment except Nil. Therefore the
coefficients β are estimated as treatment effect of the intervention compared
to Nil. In estimating the treatment effect of drug i against drug j we write
β i − β j and all the other X equal 0.
18
19
For the estimation of this regression we follow Lumley335 and use the library
nlme33 of the R419 software.
14
15
16
20
21
3. Estimates of incoherence
22
23
24
25
26
27
The estimate of incoherence (the standard error ω of the interaction effect) is
reported in Table 4 for the four models. It can be noticed, that although this is
slightly higher for major bleeding, the estimates are all small compared with
the standard errors of the estimates of treatment effect (Table 4), suggesting
that there is a high degree of consistency among the results of the included
trials.
28
Table 4: Estimates of Incoherence
Outcome
DVT single
DVT combined
DVT combined+Double
Major Bleeding
Incoherence (standard
error)
0.003
0.002
0.0005
0.008
29
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APPENDIX G
2
Cost-effectiveness analysis - methods
3
4
5
6
7
1. General approach
Our aim in constructing the model was to determine the most cost-effective
thromboprophylaxis strategy for different surgical scenarios. We took a fourstage approach:
8
1. Comparing the different drug interventions
9
2. Evaluating mechanical prophylaxis
10
11
3. Evaluating the addition of a drug as an adjunct to mechanical
prophylaxis.
12
13
4. Evaluating drug prophylaxis in the post-discharge period in high risk
groups.
14
15
16
The thromboprophylaxis interventions we compared in the model are
essentially those which we evaluated in our mixed-treatment comparisons
meta-analysis (Chapter 11).
17
18
The primary outcomes are quality-adjusted life-years (QALYs) gained and
incremental cost.
19
General methodology:
20
21
• The effects were derived from the mixed treatment comparisons metaanalysis reported in chapter 12.
22
23
24
• We performed a probabilistic sensitivity analysis to test the robustness of
the results to the imprecision of these estimates and the other model
parameters.
25
26
27
28
29
• The model employed a cost-effectiveness threshold of £20,000 per
QALY gained, complying with the reference case advocated by NICE379,
such that costs were estimated from an NHS and personal social
services perspective and both future costs and QALYs are discounted at
3.5%.
30
Time horizon:
31
32
33
For our base case analysis we considered only the cost and health effects of
events taking place during the trial observation period. The events included
were:
34
• Symptomatic DVTs
35
• Symptomatic pulmonary emboli
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o Fatal
2
o Non-fatal
3
• Major bleeding events
4
o Fatal
5
o With long term morbidity (e.g. stroke)
6
o No long-term sequalae.
7
8
9
10
11
The incidence of symptomatic VTEs is assumed to be in fixed proportion to
the incidence of DVTs, such that for scenarios with a lower incidence of DVT
there will be proportionately lower incidence of fatal PE, etc. Likewise the
incidence of fatal bleeding events is assumed to be in fixed proportion to the
incidence of major bleeding events.
12
13
14
15
16
17
18
19
20
21
22
Sullivan489 recommends that thromboprophylaxis models adopt two different
time horizons: short-term and five-years. As a sensitivity analysis we estimate
events taking place over five years (recurrent VTE and post-thrombotic
syndrome). While there is no direct RCT evidence, it is hypothesised that
strategies that reduce DVT lead to a similar reduction in the incidence of
recurrence and PTS. The short-term model has the advantage that the results
are mostly observed within the RCTs. The five-year model involves
extrapolation from the trial results but is intended to capture more elements of
health gain and cost impact. We estimate the five-year results using a Markov
model36 where we assume for simplicity that the incidence of post-thrombotic
syndrome and recurrence is constant up to 5-years.
23
24
25
26
27
28
29
2. Relative risks
The between-strategy differences in costs and effects are driven by each
strategy’s relative risk reduction for DVT and its relative risk increase for major
bleeding. We used the relative risks estimated using our mixed treatment
comparisons meta-analysis (Chapter 12). However, we have also sought to
estimate the results for fondaparinux in combination with a mechanical device.
30
31
Key assumptions
32
33
34
1. We make the assumption that the relative risk (RR) change of each
prophylaxis strategy is constant regardless of type of surgery and therefore
we pool together the results of RCTs from all surgical categories.
35
36
37
2. Not every study collected PE data and given the rarity of the event, relative
risks are imprecise, so we assumed that the relative risk reduction in
symptomatic PEs (fatal and non-fatal) is exactly the same as for DVTs.
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2
3. Similarly we assumed that the RR increase in fatal bleeds and strokes
would be exactly the same as for major bleeding overall.
3
4
4. For our main analysis, we assume prophylaxis does not reduce the
incidence of PTS or VTE recurrence.
5
6
7
5. We assume that prophylaxis is continued until discharge. Prophylaxis cost
is sensitive to length off stay; however, we assume the same RR reduction
regardless of the length of stay.
8
9
10
11
12
13
14
We found some evidence to support Assumption 2, for heparin, at least,
Figure 182 shows a RR for fatal PE for unfractionated heparin vs nil of 0.42
(0.22, 0.66) that’s comparable to the RR for DVTs (Chapter 6) of 0.44 (95%
CI: 0.38 to 0.52, 61 studies). However, this analysis of fatal PEs is less
reliable than the data from our systematic review because the data was
extracted from a previous systematic review104 and it is unlikely that all the
events were confirmed by autopsy or other objective test.
15
16
17
For each strategy the results are given relative to the nil prophylaxis strategy.
The nil prophylaxis strategy data is taken from both placebo and open noprophylaxis trial arms.
18
Figure 182: Fatal pulmonary embolism in trials of unfractionated heparin vs nil
19
20
21
22
We assume that the major bleeding rate for mechanical only strategies is the
same as for the nil strategy.
23
24
25
26
The estimates of RR are presented in chapter 12. For extended prophylaxis
beyond discharge the data was more limited and therefore we simply used the
relative risks compared with no post-discharge from our direct comparison
meta-analyses (Chapter 6).
27
28
29
There were no RCTs that explicitly evaluated the adjunctive benefits of
fondaparinux over mechanical prophylaxis. We derived an approximate DVT
RR reduction for this combination because of key interest is the addition of an
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3
4
effective drug to a mechanical intervention and it is highly plausible that the
combination would be more effective since each one operates by a very
different mechanism. We assumed that adding a mechanical to Fondaparinux
has the same relative effect as adding a mechanical to LMWH:
5
RRF+MvNil= RRFvNil( RRL+MvNil / RRLvNil)=0.21(0.26/0.38)=0.14
6
7
8
9
10
11
12
3. Baseline risks
13
14
15
16
17
18
19
20
21
22
23
24
25
There was little data to estimate the post-discharge DVT risk. We estimated
the post-discharge baseline DVT risk (i.e. the post-discharge risk assuming
LMWH is used during the hospital stay only) to be 21% (117/556) in elective
hip patients 43,118,246,311,340,408. This was a ratio of 1:2 (21%:45%) compared
with the pre-discharge baseline risk in elective hip surgery; for other types of
surgery we assumed that post-discharge baseline risk is half that of the predischarge risk. Similarly the post-discharge baseline risk of symptomatic PE
was 1% (6/628) in elective hip patients; a ratio of 1:4 (1%:4%) compared with
the pre-discharge baseline risk. There wasn’t enough data on post-discharge
bleeding to distinguish between different types of surgery so we estimated a
baseline risk from the nil arm of the LMWH and fondaparinux post-discharge
studies) and assumed it to be constant across surgical categories: 0.1%
(1/722)42,143,340,499.
Effectiveness and cost-effectiveness is dependent on the absolute risk
reduction and absolute risk increase rather than just the relative risk (RR)
changes. To estimate absolute risk changes, the model multiplies the RR
changes pooled from across all RCTs by the surgery-specific baseline risk.
The baseline risk of DVT, symptomatic PE and major bleed, were estimated
from the no prophylaxis arms of the RCTs in our clinical review (Chapter 4).
26
27
28
29
4. Symptomatic events
30
31
32
33
34
35
In one of our sensitivity analyses, we included the costs and effects up to fiveyears. We could not find data on the rate of VTE recurrence after
asymptomatic VTE. We decided to be conservative and assume that the
prevention of asymptomatic VTEs does not lead to prevention of recurrence in
later years. However for PTS and for recurrence after symptomatic DVT we
assumed a RR reduction identical to the DVT RR reduction. .
To estimate the incidence of symptomatic events (Table 5), we looked for
good quality systematic reviews, RCTs or cohort studies for each parameter.
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Table 5: Symptomatic events
Event
Probability
Source
Hip fracture
=9/29=31%
Other surgery
=11/184=6%
HTA report – Roderick
(2005)430
5/632=1%
Muntz (2004)377
3%**
Personal communication
from Muntz & Scott
Method
Prevalence of acute
events
Proportion of
symptomatic PEs that
are fatal*
Proportion of major
bleeds that are fatal
(prophylaxis)
Proportion of major
bleeds that lead to
chronic morbidity (i.e.
non-fatal strokes)
Proportion of major
bleeds that require reoperation
Proportion of DVTs that
are symptomatic
25/118=21%
2.6%/17%=15%
Muntz (2004)377
Numerator
(38/1516)=Colwell
(1999)105,
Denominator=expected
DVT rate with LMWH
prophylaxis
Systematic review of
thromboprophylaxis
RCTs
Systematic review of
thromboprophylaxis
RCTs
Systematic review of
thromboprophylaxis
RCTs
Systematic review of
thromboprophylaxis
RCTs
Numerator=RCT
Denominator=
Systematic review of
thromboprophylaxis
RCTs
Incidence of PTS & recurrence (for use in sensitivity analysis but not the base case analysis)
528 consecutive
24.3% x 0.65=16%
patients with
(where 0.65 is the
venographically
RR for surgical
confirmed symptomatic
patients cf all
5-year recurrence rate
DVT followed for 8
patients with
after symptomatic VTE
years
symptomatic VTE)
Prandoni (1997)417
5-year PTS rate after
symptomatic VTE
As above
30%
Prandoni (1997)417
Meta analysis of cohort
studies (n=364). NB
follow-up was 2-10
5-year PTS rate after
21%
Wille-Jorgensen (2005)547 years
asymptomatic VTE
2
3
4
5
6
7
8
9
10
11
*.There were not enough data to estimate a different rate for every type of surgery, however, we estimated a
separate rate for hip fracture, since it has been recognised that events are more likely to be fatal in frail trauma
patients.
** Major bleeds were originally recorded as at site of operation, GI or ‘other site’. The stroke rate was estimated as
the product of the following two components:
a) The ratio of ‘other site’ to all sites=83/378
b) The ratio of stroke to all ‘other site’=2/13
The numerator of b) is smaller than the denominator of a) because in the majority of cases the exact site was not
recorded.
12
13
14
15
5. Resource use & cost - prophylaxis
16
17
18
19
The duration of the intervention in the RCTs was usually until discharge. We
have used the mean length of stay for each surgery type to determine the cost
of the prophylaxis per patient, but this does vary considerably. According to
Hospital Episode Statistics (HES), in 2004 there was a mean length of stay 10
The unit costs of mechanical prophylaxis are given in Table 6. Drug prices
were taken from the current BNF260 (Table 7) for the recommended thromboprophylactic dose.
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2
3
4
days for elective hip and 20 days for hip fracture. This means that the inhospital prophylaxis duration and cost is greater for hip fracture because
these patients are immobile for longer but this should be reflected in the
events averted.
5
6
We added the cost of nurse time and monitoring tests for each intervention
(see Table 8).
7
8
9
10
11
12
For extended prophylaxis, we assumed that LMWH or fondaparinux
prophylaxis would be continued for 21 days beyond discharge. We also
assumed that 8% of patients would require daily visits from the district nurse
to give the injection. This is on the basis of two surveys, which both found that
8% of patients could not comply with administering their own LMWH
prophylaxis106,477 (Chapter 6).
13
14
The total cost of each prophylaxis strategy, assuming a length of stay of 7
days, is shown in Table 9.
15
Table 6: Mechanical prophylaxis unit costs
16
17
Graduated compression stockings (knee
length, class 2) – 1 pair per patient
Intermittent pneumatic compression
(equipment )
Intermittent pneumatic compression (sleeves) 1 pair per patient)
Cost
£9
£865*
Source
NHS Electronic Drug Tariff –
Feb 2006
Huntleigh Healthcare
£20
Huntleigh Healthcare
* The implied rental value is £309 per annum, assuming life expectancy for the equipment of 3 years and an interest
rate of 3.5%. The equipment cost per patient is the rental value multiplied by the patient’s length of stay.
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Table 7: Pharmacological prophylaxis – information and prices from the BNF
March 2006
Drug
Dose
Injections
per day
Drug cost
per day
UFH
5000 U sc every 8 hours for 7 days or
until ambulant
3
£1.41
LMWH*
Varies by specific drug
1
£3.84
Fondaparinux
sodium
2.5mg sc daily 5-9 days post surgery
(longer after hip surgery)
1
£6.66
Danaparoid
sodium
750 U sc 2x daily 7-10 days
2
£59.60
Oral
anticoagulant
(Warfarin)
Aspirin
Dose is adjustable.
[Assumed average of 4mg per day]
N/A
£0.09
Aspirin is not licensed specifically for
thromboprophylaxis [A typical aspirin
dose from the RCTs in our review is
1000mg**]
N/A
£0.14
3
4
5
6
7
8
* This cost is for the dosages designated in the BNF as suitable for high-risk patients. The studies in our clinical
review included a variety of dosages; some substantially lower than this and some substantially higher.
** Later studies have used lower doses and have considered aspirin as adjunctive prophylaxis but the data in our
meta-analysis was from earlier studies where aspirin was the main source of prophylaxis. The affect on prophylaxis is
however negligible given the cheapness of aspirin.
9
Table 8: Prophylaxis - testing & nurse time
Drug
Tests required
Cost of test
(North
Middlesex
Hospital)
UFH
Full blood count: baseline
(+day after start if previous
exposure to UFH) then
alternate days from day 4-14
(BCSH guidelines, Keeling
2006277,278)
Full blood count: baseline
then Every 2-4 days until day
14 (BCSH guidelines, Keeling
2006277,278)
-
£4.04
LMWH
Fondaparinux,
Danaparoid
Nurse time
associated with
administering
and monitoring
prophylaxis
2-3 minutes per
injection
£4.04
2-3 minutes per
injection
-
2-3 minutes per
injection
Oral
anticoagulant
(Warfarin)
Aspirin
INR tests: approximately 3
per week during hospital stay
£4.54
10-20 minutes
per day
-
-
2-3 minutes per
day
Mechanical
-
-
5-10 minutes per
day
10
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Table 9: Prophylaxis costs
Cost per patient
(drugs, consumables,
equipment, tests, nurse time)
Aspirin
UFH
LMWH
OAC-adj*
Fondaparinux
Danaparoid
Stockings
IPCD
Mechanical
(Mean of Stockings & IPCD)
2
3
4
5
6
7
8
9
10
11
12
13
Generic
patient
(7 days)
£7
£44
£45
£51
£53
£429
£26
£43
£34
(21 days)
LMWH (post-discharge)
£115
Fondaparinux
£174
*OAC-adj=adjustable-dose oral anticoagulant
6. Resource use & cost – treatment
To devise resource use protocols for diagnosing and treating VTEs we
examined the BTS guidelines on the management of PE78 and British
Committee for Standards in Haematology (BCSH) guidance on the
prophylaxis and treatment of DVT277,278. Members of the GDG helped develop
treatment protocols that could be costed. We have sought to develop
protocols that would be considered achievable good practice currently in the
NHS. Unit costs were taken from standard NHS sources: NHS reference
costs132, BNF260, NHS Electronic Drug Tariff 381, PASA382, Curtis and Netten
2005116 (Table 10).
14
15
16
17
18
For post-thrombotic syndrome (PTS), recurrence and stroke, the treatment
pathways are varied and complex and therefore we took from the literature
costs estimated from relevant cohort studies of patients (Table 11). In the
case of PTS and recurrent VTE we did not find a suitable cohort based in the
UK and therefore used a Swedish study instead.
19
20
21
22
23
24
25
The cost of treating major bleeding was assumed to vary primarily according
whether there was a need to re-operate (Table 11). We hypothesised that the
cost of treating major bleeding might vary by prophylaxis strategy due to
substantial differences in the cost of antidotes. But in the end we decided that
this would be difficult to substantiate, especially given that the prophylaxis is
unlikely to be identified as the main cause of the major bleeding. So antidote
costs were not explicitly incorporated.
26
27
In Error! Reference source not found. are the estimates of total treatment
costs for each event, derived from the above data and assumptions.
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Table 10: VTE diagnosis and treatment costs
Symptomatic
DVT
Non-fatal
Symptomatic
PE
Source for
resource use
Unit
cost
Source for unit
cost
£99 per
test
£81 per
test
£25 per
test
£19 per
test
NHS reference
costs 2005
NHS reference
costs 2005
NHS reference
costs 2005
NHS reference
costs 2005
Diagnosis
-
1
Published
guidelines
Published
guidelines
Chest x-ray
-
1
Expert opinion
ECG
Treatment
-
1
Expert opinion
Doppler ultrasound
CT pulmonary
angiogram
-
LMWH
7 days
7 days
Published
guidelines
£8.02
per day
Mean of
treatment dose
regimens - BNF
March 2006
Full blood count
2
3 months x
69% (distal)
6 months x
31%
(proximal)*
2
Expert opinion
£4.04
per test
North Middlesex
Hospital
£0.09
per day
BNF March 2006
10% x 4 days
90% x 30
minutes
90% x 6 days
Published
guidelines
VERITY
database*** for
% / NHS
reference
costs 2005 for
LOS
£179 per
day**
NHS reference
costs 2005
10% x 30
minutes
Expert opinion
£21 per
hour
Curtis and
Netten 2005
-
10% x 7days
Expert opinion
£1,470
per day
NHS reference
costs 2005
Graduated
compression
stockings
6 pairs over 2
years
6 pairs over 2
years
Expert opinion
Anticoagulation
clinics (including
cost of INR testing)
Distal = 5
visits
Proximal = 7
visits
7 visits
Expert opinion
5-10% of
visits
Portsmouth
and North
Middlesex
hospitals
2005/6
Warfarin
Extended hospital
stay
Instruction on selfadministration of
LMWH (nurse
time)
ICU stay
2
3
4
5
6
1
Ambulance
transport to
anticoagulation
clinic
5-10% of
visits
6 months
£9 per
pair
£32 first
visit; £26
for each
follow-up
visit
£34 for
return
visit
NHS Electronic
Drug Tariff – Feb
2005
NHS reference
costs 2005
London
ambulance
charge May
2006
(wheelchair
assisted)
* The ratio of proximal DVTs to all DVTs was estimated from the RCTs in our review that reported the incidence of
both: (1,991/34,704)/(6,467/35,256)=(6%/18%)=31%
** Average cost of an excess bed-day for HRG codes D10, D11, E20, E21 (elective and non-elective).
522
*** National Venous Thromboembolism Registry
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Table 11: Other treatment unit costs
Event
Unit cost
Source
Stroke
£7,744
Grieve et al (2000)196
PTS
£4,000
Bergqvist et al (1997)51
Recurrent VTE
£5,000
Bergqvist et al (1997)51
Major bleeding with
re-operation
£2,133
NHS reference costs
2005132
Major bleeding
without re-operation
£901
NHS reference costs
2005132
Method
328 NHS patients followed
prospectively for 12 months after
stroke (inflated to 2005 prices)
Retrospective cohort study of
250 Swedish patients followed
for 15 years after first
symptomatic DVT (converted to
UK£ and inflated to 2005 prices)
As above
Mean cost of a GI bleeding with
major procedure (HRG codes:
F61, F62 non-elective and
elective)
Mean cost of a GI bleeding
treatment episode (HRG codes:
F64, F65 non-elective and
elective)
2
3
Table 12: Summary of the consequences of each event
Events
Fatal PE
Fatal bleed
Symptomatic DVT
Symptomatic PE (non-fatal)
Major bleed (stroke)
Major bleed (other non-fatal)
Additional
treatment
cost
QALYs lost
(Generic
patient)
£0
£0
7.730
7.730
£476
£2,498
£7,744
£1,160
0.004
0.017
0.320
0.011
4
5
6
7. Life expectancy
Naturally for patients dying during hospitalisation expected life-years is zero.
7
• Fatal pulmonary embolism
8
• Fatal bleeding event
9
10
For patients surviving surgery we estimated life expectancy using a
combination of surgery-specific and population data (Table 13).
11
12
13
• Life tables based on mean age & sex distribution of patients undergoing
surgery, separately for each of five common categories of surgery
(source of age/sex: NHS Hospital Episode Statistics131)
14
15
• From 12 months we have to assume age/sex-specific life expectancy for
England & Wales (Source: Government Actuary Department194)
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2
3
4
• For the first 12 months we applied standardised mortality ratios
(Seagroatt & Goldacre, 1994464) to the relevant E&W mortality rate, so
that for the first year after surgery we are using-surgery-specific
mortality.
5
6
7
• Another adjustment was then made to subtract from this mortality the
mortality already captured in the model, so that we don’t double count
deaths.
8
Table 13: Data for estimating life expectancy
HES code
9
10
11
Elective
hip
Hip
fracture
Elective
cholecystectomy
Elective
abdominal
hysterectomy
Elective
inguinal
hernia
repair
Standardised
Mortality Ratio
(in 12 months
after
surgery)*464
Mean
age at
surgery
(HES
20045)131
% Male
(HES
20045)131
83% (71, 97)
461% (432,
491)
70
38%
82
21%
Men aged 70: 13.0
Women age 70: 15.4
Men aged 82: 6.4
Women age 82: 7.7
105% (85, 129)
52
24%
Men aged 52: 26.9
Women age 52: 30.6
77% (50, 114)
50
0%
Men aged 50: 28.7
Women age 50: 32.4
81% (70, 92)
52
92%
Men aged 52: 26.9
Women age 52: 30.6
W37, W38
W46, W47,
W48
JB1
Life expectancy (GAD
2002-4: England &
Wales)194
Q07.4
TB1
* Ratio of the death rate in the surgical group compared with the death rate in the general population, adjusting for
age and sex.
12
13
14
15
16
17
8. Quality of life weightings
18
19
20
21
22
23
24
To estimate lost quality of life for acute events, we followed the approach
taken in a number of earlier models, where the quality of life lost is assumed
to be equivalent to a complete loss of quality of life during the hospital stay.
This does perhaps over-estimate the loss of quality of life attributable to both
VTEs and major bleeding but empirical values are not present in the literature
and besides the results are dependent much more on the impact of fatal
events than on short-term morbidity.
25
26
27
For patients with no event, we used the population average quality of life for
England and Wales measured using the EQ5D, a widely used and validated
measure of overall health-related quality of life.
We have sought to find quality of life weightings in the published literature,
firstly by looking at source data for cost-utility studies included in our review
and also by searching the Cost-effectiveness Analysis Registry’s Catalog of
preference scores2. The scores in Table 14 were combined with the life
expectancy data in Table 13 to estimate QALYs.
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For other long-term states we took scores from well-conducted studies in the
published literature.
3
4
The impact of each event on quality-adjusted life-expectancy is summarised in
Error! Reference source not found. above.
5
Table 14: Quality of life weightings
Health state
No long term event
(general population
average)
Stroke (1st year)
Quality of life
score
(0=death,
1=full health)
0.82
Method / popn
0.50
a) EQ5D, 3086 stroke patients in an
RCT496
b) Standard gamble 36 patients with and
without symptomatic DVT391
c) Standard gamble, 30 doctors & 30
volunteers323
d) Time trade-off, 70 patients with atrial
fibrillation174
e) EQ5D, patients in RCT receiving
warfarin or aspirin397
a) Standard gamble 36 patients with and
without symptomatic DVT391
b) Standard gamble, 30 doctors & 30
volunteers323
Assumed
PTS
0.82x0.97=0.80
During extended hospital
stay for symptomatic VTE
or major bleeding
Warfarin treatment after
symptomatic DVT
Recurrent VTE
0
0.82x0.99=0.81
0.81
EQ5D instrument completed by 3395
people resident in the UK291
Time trade-off, 70 patients with atrial
fibrillation174
Assumed to be the same as warfarin
treatment after symptomatic DVT
6
7
8
9. Sensitivity analysis
To examine the robustness of the model, we did the following:
9
• produced base case results for five different surgical scenarios
10
• conducted a probabilistic sensitivity analysis for each scenario
11
12
• conducted three-way deterministic sensitivity analyses for the ‘generic’
surgical patient
13
Surgical scenarios
14
15
16
17
18
19
Error! Reference source not found. summarises all of the differences
between types of surgery that are captured by the model. Age, sex and
standardised mortality ratio contribute to the estimates of life expectancy and
subsequently the magnitude of QALYs gained from averting a fatal PE and
the magnitude of QALYs lost from incurring a fatal bleeding event. Length of
stay impacts on the cost of prophylaxis. The baseline risk of events affects the
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magnitude of treatment costs (or savings) and the magnitude of QALYs
gained (or lost). In addition to five specific types of surgery we also
constructed a category that we believe is a more typical surgery patient, which
we have labelled ‘generic’.
5
Probabilistic sensitivity analysis (PSA)
6
7
We used our data to estimate the standard error and distribution of each
parameter in our model. (
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
Table 16). We then sampled randomly from all these distributions
simultaneously re-estimating the key outcome variables (incremental cost and
QALYs gained for each prophylaxis strategy). We then repeated this 10,000
times so that we have a distribution for our results as well as a (deterministic)
point estimate. This process is known as Monte Carlo simulation. With this
information we can ask the question: in what proportion of simulations was a
particular strategy cost-effective. This is not an exact science, not least
because we assume that all of the model parameters are independent, when
there could be substantial covariance. However, it still gives us an
appreciation of the uncertainty around our results. For simplicity the following
variables, were left deterministic (i.e. were not varied in the probabilistic
sensitivity analysis: age, % male, standardised mortality ratio (SMR) (since
these were deemed to be fixed by the scenario) and drug prices (which were
subject to a deterministic sensitivity analysis – see below), the discount rate
and cost-effectiveness threshold (which were deemed to be fixed by NICE).
23
24
25
26
27
One way of presenting the uncertainty explored by a PSA is to plot 95%
confidence ellipses in the cost-effectiveness plane (i.e. a graph that has
incremental cost on the vertical axis and QALYs gained on the horizontal
axis). These are two-dimensional outlines that indicate the limit of 95% of our
Monte Carlo simulations.
28
29
30
31
32
33
34
35
36
37
We followed the approach of Van Hout (1994)517, that is, assuming that the
costs and effects follow a joint normal distribution. (A visual inspection of the
simulations on a scatter plot confirmed that a joint normal distribution is
plausible for this data set). To plot the ellipses, we used the library ‘ellipse’ of
the free statistical software R. In order to determine the confidence intervals,
and assuming a bivariate normal distribution on both costs and QALYs, we
need five parameters that are calculated from our 10,000 simulations: mean
difference in QALYs, mean difference in costs, standard deviation of the
incremental costs, standard deviation of incremental QALYs and their
correlation.
38
39
40
41
42
43
44
While a confidence ellipse does indicate the extent of our uncertainty, overlap
between two ellipses does not have much meaning because some of the
variability in the model parameters (for example, baseline risk) affects different
strategies in the same manner. And hence one strategy could be better than
another in almost every simulation and yet the intervals overlap considerably.
We therefore produced additional ellipses that reflect only the variability in our
estimates of RR for each strategy. In these plots, substantial overlap between
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the ellipses of two different strategies does indicate that there is great
uncertainty about which strategy is the most cost-effective.
3
Deterministic sensitivity analysis
4
5
6
7
8
9
10
11
It is obvious that the effectiveness and cost-effectiveness of prophylaxis will
be highly dependent on the baseline risk of VTE and the baseline risk of major
bleeding. Therefore we present the results for the ‘generic’ patient in the form
of a grid that indicates the optimal strategy for different levels of risk (keeping
all other variables constant and keeping symptomatic PEs as a fixed
proportion of DVTs: 10.5%). We then produced this grid a number of times;
each time changing a key assumption in the model. The assumptions that
were tested were:
12
• We used discounted drug prices instead of the BNF list price.
13
• We assumed a major bleeding fatality rate of 5% instead of 1%.
14
15
• We assumed mechanicals are only 50% as effective at reducing fatal
PEs as they are at reducing DVTs.
16
17
• We excluded the most effective combination strategy: Mech +
fondaparinux.
18
19
• We included estimates of the impact on post-thrombotic syndrome &
recurrence.
20
21
• We included single drug strategies in our final analysis as well as
combination strategies.
22
Table 15: Surgical scenarios: summary of differences
Mean age
(years)
% Male
Standardised
Mortality
Ratio (1st year)
Mean LOS
(days)
DVT risk
Symptomatic
PE risk
Major bleeding
risk
Fatal PE / All
symptomatic PE
Hip
Fracture
Elective
Hip
Hysterectomy
Cholecystectomy
'Generic'
82
21%
70
38%
50
0%
52
24%
60
50%
4.6:1
0.8:1
0.8:1
1.1:1
1:1
20
39%
10
45%
6
16%
4
6%
4%
1%
2%
3%
2%
4%
2%
31%
7
25%
6%
23
24
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Table 16: Distributions for model parameters used in the probabilistic sensitivity
analysis
Parameter
Distribution Distribution Assumptions
fitted
properties for distribution parameters
Costs
Gamma
Left skewed -Mean: as for the base case
-Se: found indirectly from
fitted CI (+/-25% Mean)
Hospital
LOS
Log-normal
Bounded at -Mean: as for the base case
zero
-Se: found indirectly from
fitted CI (+/-25% Mean)
Relative risks Log normal
Log RR is
Normally
distributed
Proportions
Beta
Quality of life
scores
Beta
Bounded (0- -Sample size of patients in
1)
the study
-number of those
experiencing the events
Bounded (0- -Sample size of patients in
1)
the study
-percentiles from study
-Mean: Log RR
-Se: standard deviation of
log RR
3
4
5
6
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