Improving Thromboprophylaxis Using Atrial Fibrillation Diagnostic

Improving Thromboprophylaxis Using Atrial Fibrillation
Diagnostic Capabilities in Implantable
Cardioverter-Defibrillators
The Multicentre Italian ANGELS of AF Project
Giuseppe Boriani, MD, PhD; Massimo Santini, MD; Maurizio Lunati, MD;
Maurizio Gasparini, MD; Alessandro Proclemer, MD; Maurizio Landolina, MD;
Luigi Padeletti, MD; Giovanni Luca Botto, MD; Alessandro Capucci, MD; Stefano Bianchi, MD;
Mauro Biffi, MD; Renato Pietro Ricci, MD; Marco Vimercati, BS; Andrea Grammatico, PhD;
Gregory Y.H. Lip, MD; on behalf of the Italian ClinicalService Project
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Background—Atrial fibrillation (AF) is a well-established risk factor for stroke and thromboembolism and is a frequent
comorbid arrhythmia in patients with implantable cardioverter-defibrillators (ICDs). The Anticoagulation Use Evaluation and
Life Threatening Events Sentinels (ANGELS) of AF project was a medical care program aimed at supporting adherence to
oral anticoagulation (OAC) guidelines for thromboprophylaxis through the use of ICD AF diagnostics.
Methods and Results—Fifty Italian cardiology clinics followed 3438 patients with ICDs. In a subgroup of 15 centers (the
ANGELS of AF centers), cardiologists attending to follow-up visits were supplied with specific reports describing stroke risk
factors and risk scores (American College of Chest Physicians and CHADS2 [congestive heart failure, hypertension, age ⱖ75
years, diabetes mellitus, and prior stroke or transient ischemic attack]), AF occurrence and duration, and current
antithrombotic therapy for patients with AF, especially those with a CHADS2 score ⬎0 and not on OAC therapy. The
remaining centers represented a control group of patients as a comparison of OAC use. In the ANGELS of AF centers, 709
(36%) patients had AF described either in their clinical history (n⫽426 [22%]) or as new-onset AF (n⫽257 [14%]). Among
683 (96%) patients with CHADS2 score ⬎0, 209 (30.6%) were not taking an OAC. Appropriate OAC therapy was prescribed
in 10% (22/209) of patients after evaluation of ANGELS of AF reports. The percentage of patients on OAC therapy, as
indicated by guidelines, increased during follow-up from 46.1% at baseline, to 69.4% at the stroke risk evaluation phase, to
up to 72.6% at the end of the observation period. In control centers, corresponding figures were 46.9% at baseline and 56.8%
at the end of the observation period (P⬍0.001 versus ANGELS of AF group).
Conclusions—The ANGELS of AF project demonstrates the possibility to improve OAC use in accordance with available
guidelines for stroke risk reduction in AF by supplying attending physicians with reports about patients risk factors and
AF information from continuous ICD monitoring.
Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01007474.
(Circ Cardiovasc Qual Outcomes. 2012;5:00-00.)
Key Words: stroke 䡲 cerebral ischemia 䡲 anticoagulants 䡲 atrial fibrillation 䡲 implantable cardioverter-defibrillators
A
trial fibrillation (AF) is the most common cardiac arrhythmia, which is increasing in prevalence and incidence.1,2
Importantly, AF has been associated with a 5-fold increase in the
risk of ischemic stroke.2,3 Effective prevention of stroke and
thromboembolism requires oral anticoagulation (OAC), although stroke risk is influenced by associated risk factors.2,3
Underuse of OAC therapy with warfarin has been shown to
occur in real-world clinical practice in patients at moderate to
high thromboembolic risk.4 – 6 Current guidelines for stroke
prevention in AF2,3,7 do not differentiate between patients
with symptomatic or asymptomatic AF or between paroxysmal or persistent AF. Continuous device monitoring has
Received September 27, 2011; accepted February 8, 2012.
From the S Orsola-Malpighi Hospital, Bologna, Italy (G.B., M.B.); San Filippo Neri Hospital, Rome, Italy (M.S.); Niguarda Ca’ Granda Hospital
Milano, Italy (M. Lunati); Istituto Clinico Humanitas IRCCS, Rozzano, Italy (M.G.); S Maria della Misericordia Hospital, Udine, Italy (A.P.); S Matteo
IRCCS, Pavia, Italy (M. Landolina); Careggi Hospital, Florence, Italy (L.P.); S Anna Hospital, Como, Italy (G.L.B.); Lancisi Hospital, Ancona, Italy
(A.C.); S Giovanni Calibita-Fatebenefratelli Hospital, Rome, Italy (S.B.); Medtronic Italia, Rome, Italy (M.V., A.G.); and University of Birmingham,
Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK (G.Y.H.L.).
Correspondence to Giuseppe Boriani, MD, PhD, Institute of Cardiology, University of Bologna and Azienda Ospedaliera S Orsola-Malpighi, Bologna
Via Massarenti 9, 40138 Bologna, Italy. E-mail [email protected]
© 2012 American Heart Association, Inc.
Circ Cardiovasc Qual Outcomes is available at http://circoutcomes.ahajournals.org
1
DOI: 10.1161/CIRCOUTCOMES.111.964205
2
Circ Cardiovasc Qual Outcomes
March 2012
shown that atrial tachyarrhythmias are frequent comorbidities in patients with implantable cardioverter-defibrillators
(ICDs)8 –10 and that the majority of AF episodes are asymptomatic, including many episodes of clinically significant
WHAT IS KNOWN
●
●
Atrial fibrillation (AF), either silent or clinically
manifest, is associated with a 5-fold increase in the
risk of ischemic stroke.
Effective prevention of stroke and thromboembolism
requires oral anticoagulation, guided by risk stratification, but underuse of oral anticoagulation with warfarin
is common in real-world clinical practice in patients at
moderate to high risk of thromboembolism.
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WHAT THIS ARTICLE ADDS
●
●
A dedicated medical care program, ANGELS (Anticoagulation Use Evaluation and Life Threatening Events
Sentinels) of AF, including use of information from
implantable cardioverter-defibrillator AF diagnostics
on AF occurrence and duration improved oral anticoagulation use compared with standard care.
This approach may be useful in improving appropriate warfarin use in patients with implantable
cardioverter-defibrillators and concomitant AF.
duration.11 However, it is unknown to what extent physicians
actually make clinical decisions driven by the arrhythmic
events detected by the implantable device.
The Anticoagulation Use Evaluation and Life Threatening
Events Sentinels (ANGELS) of AF project was a medical care
program aimed at improving OAC use as thromboprophylaxis
through the use of information from ICD AF diagnostics. The
main objectives of the ANGELS of AF project were to (1)
evaluate the prevalence of AF and stroke risk factors and their
association with OAC use in the followed patient population; (2)
measure the annual rate of stroke, transient ischemic attacks
(TIAs), and embolic complications; and (3) implement a strategy
for improvement of OAC therapy.
Methods
Patients included in the present analysis were followed in a network
of 50 Italian cardiological centers that participate to the Italian
ClinicalService Project. This national cardiovascular data repository
and medical care project aims to describe and improve the use of
ICDs in Italian clinical practice. The project was approved by each
site’s institutional review board or medical director and conforms
with the principles outlined in the Declaration of Helsinki. Each
patient signed informed consent for data collection and analysis.
All patients received a dual- or triple-chamber ICD for primary or
secondary prevention of sudden cardiac death, according to guidelines.9 All patients had an atrial lead, which was necessary for atrial
diagnostic capability, and were followed for at least 6 months.
Data were prospectively acquired. Patient baseline characteristics
and pharmacological treatment were collected at device implant,
whereas data collection on clinical outcomes, such as stroke, TIAs,
and embolic complications and pharmacological changes, occurred
in the follow-up period during scheduled or unscheduled hospital
visits or through phone calls to patients who missed scheduled visits.
AF detection was programmed to guarantee memorization of atrial
tachyarrhythmia data if the atrial rate was ⬎171 beats per minute for
at least 32 ventricular events in which the AV pattern showed
evidence of an atrial arrhythmia (ie, ⬎1:1 conduction). High sensitivity and specificity of AF detection algorithms in the devices used
has been previously demonstrated.10 Device diagnostics allowed for
the measurement of AF occurrence and duration in each day of the
observation period.
Project Design
Fifty Italian cardiology clinics included in the project 3438 consecutive patients with ICDs and followed them according to standard
clinical practice protocols of follow-up visits. Of these clinics, 15
received reports about AF occurrence and duration, stroke risks
factors, and OAC use and, thus, comprised the active intervention
arm of the project (Figure 1). The remaining 35 cardiological centers
prospectively followed their patients according to their center’s
standard clinical practice without reports and comprised the usual
care control arm of the project.
For patients involved in the active intervention arm, an automatic
algorithm periodically evaluated patient AF history; this information
was collected as a baseline condition or as evidence derived from
device diagnostics at follow-up visits. In the latter case, a minimum
daily AF duration of 6 hours was required to indicate a patient with
clinically significant AF because this cutoff was considered to be
associated with a relevant stroke risk, as shown in the TRENDS
study.12 For each patient with AF, an automatic algorithm estimated
American College of Chest Physicians13 and CHADS2 (congestive
heart failure, hypertension, age ⱖ75 years, diabetes mellitus, and
prior stroke or TIA)3,14 stroke risk scores. If the patient was at high
or moderate stroke risk, an automatic algorithm was used to assess
current pharmacological data to evaluate whether the patient was
taking appropriate antithrombotic agents according to current guidelines. In the case of a patient with AF with moderate of high stroke
risk and without OAC protection, an automatic algorithm produced
a report on the patient’s risk factors and on AF daily history for the
last 14 months, which was submitted to physicians involved in
the follow-up of that patient. During their hospital visit, physicians
were requested to fill out a questionnaire confirming the absence of
the OAC therapy, stating the antithrombotic therapy assigned to the
patient in that visit and for patients discharged without OAC and
explaining the reason for not administering the OAC therapy.
Statistical Analysis
Investigators had the ability to query any aspect of the data; authors
had direct access to the primary data when reporting results of the
research. Descriptive statistics were reported as mean⫾SD for
normally distributed continuous variables or median with interquartile range in the case of skewed distributions. Normality of distribution was tested by calculating skew and kurtosis values. Absolute
and relative frequencies were reported for categorical variables.
Comparisons of categorical variables were performed by means of
the Fisher exact test for extreme proportions; otherwise, the ␹2 test
was used. For statistical analysis, Stata/SE version 11.0 for Windows
(StataCorp) software was used.
Results
A total of 3438 patients were prospectively followed in this
project (Figure 1) of whom 1961 (57%) were followed in the
ANGELS of AF centers (active intervention arm) and 1477
(43%) were in the usual care control arm (Table 1). The median
follow-up duration was 25 months (interquartile range, 14 – 41
months), with a total follow-up of 9118 patient-years.
Figure 1 shows the flowchart of the project, whereby the
active intervention arm comprised 1961 patients of whom
709 (36%) had AF either described in their preimplant
clinical history (426 [22%]) or observed during follow-up
(283 [14%]) as a new onset of AF lasting ⬎6 hours. In total,
Boriani et al
Improving Oral Anticoagulation Use in ICD Patients
3
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Figure 1. ANGELS (Anticoagulation Use Evaluation and Life Threatening Events Sentinels) of AF flowchart. ACCP indicates American
College of Chest Physicians; AF, atrial fibrillation; CHADS2, congestive heart failure, hypertension, age ⱖ75 years, diabetes mellitus,
and prior stroke or transient ischemic attack; FU, follow-up; OAC, oral anticoagulation.
683 patients were at moderate to high stroke risk, and 474
(69.4%) patients were on OAC therapy. For the remaining
209 patients who were not on OAC therapy, ANGELS of AF
reports were supplied to attending physicians.
ANGELS of AF reports were the specific trigger for
altering antithrombotic therapy in 24 patients (Figure 2).
Specifically, appropriate OAC therapy was prescribed in 22
of 209 (10.5%) patients, and antiplatelet therapy was started
in 2 (1.0%) patients. In 158 (75.6%) patients, antiplatelet
therapy was confirmed as the best therapeutic choice, and in
27 (12.9%) patients, no antithrombotic therapy was prescribed. In the active intervention arm, the percentage of
patients on OAC therapy, as indicated by guidelines, increased during the follow-up from 46.1% at baseline, to
69.4% in the stroke risk evaluation phase, to up to 72.6% at
the end of the observation period (Figure 3). In the usual care
control arm, the percentage of patients on OAC therapy was
46.9% at baseline and 56.8% at the end of the observation
period (P⬍0.001 versus active intervention arm).
Stroke, TIA, and Embolic Events
During the follow-up period, 37 embolic events in 33 patients
were recorded (17 ischemic stroke, 10 TIAs, and 10 periph-
eral thromboembolic complications). Among 1174 patients
with a history of AF or new-onset AF, 22 experienced 25
embolic events (8 ischemic strokes, 9 TIAs, and 8 peripheral
thromboembolic complications). The annual rate of patients
with embolic events was 0.7 per 100 patient-years; in the
remaining 2264 patients who never experienced an AF, in a
total follow-up of 5367 patient-years, 11 experienced ischemic strokes, TIAs, or thromboembolic complications, with an
annual rate of 0.2 per 100 patient-years (P⫽0.001 versus
patients with AF).
Among 33 patients with stroke, TIA, or embolic events, 21
(64%) had at least an AF lasting at least 5-minutes, as
detected by ICD diagnostics, in the observation period
preceding thromboembolic events. When evaluating the 30
days preceding the thromboembolic events, 11 (33%) patients
experienced AF. Finally, 5 (15%) patients experienced embolic events during AF.
The annual rate of patients with embolic events in a subgroup
of 1174 patients with a history of AF or a new-onset AF is
shown in Table 2 in relation to CHADS2 score and antithrombotic therapy. In patients with a CHADS2 score of 1 to 2, the
annual rate of patients with embolic events was 2 of 934 (0.2%)
with OAC and 8 of 1011 (0.8%) without OAC (P⫽0.11).
4
Circ Cardiovasc Qual Outcomes
Table 1.
March 2012
Baseline Patient Characteristics
Characteristics
Overall
Population
(n⫽3438)
Active
Intervention
Arm
(n⫽1961)
Male sex
2802 (82)
1608 (82)
71⫾11
71⫾11
Heart failure
2790 (81)
1532 (78)
1258 (85)
Vascular disease
1814 (53)
1022 (52)
792 (54)
Hypertension
1571 (46)
809 (41)
762 (52)
389 (19.8)
346 (23.4)
Age, y
Control
Arm
(n⫽1477)
1194 (81)
73⫾6
Comorbidities
Diabetes
735 (21.4)
Prior stroke/TIA
135 (4)
81 (4)
54 (4)
Atrial fibrillation
713 (21)
426 (22)
287 (19)
1597 (46)
904 (46)
693 (47)
Drug therapies
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Anticoagulant therapy
Acenocoumarol
Warfarin
Antiplatelet therapy
Diuretics
364 (10)
202 (10)
162 (11)
1234 (36)
702 (36)
532 (36)
789 (23)
477 (24)
312 (21)
3310 (96.3)
1891 (96.4)
1419 (96.1)
␤-blockers
2797 (81)
1561 (80)
1236 (84)
ACE inhibitors
2747 (80)
1571 (80)
1176 (80)
Antiarrhythmic therapy
1648 (48)
935 (48)
713 (48)
Data are presented as n (%) or mean⫾SD.
TIA indicates transient ischemic attack; ACE, angiotensin-converting
enzyme.
Among 709 patients with a history of AF or a new-onset
AF in the active intervention arm, 14 experienced embolic
events in 2200 patient-years, with an annual rate of 0.64 per
100 patient-years. Among 465 patients with a history of AF
or a new-onset AF in the usual care control arm, 8 experienced embolic events in 960 patient-years, with an annual
rate of 0.83 per 100 patient-years (P⫽0.64).
Post Hoc Analysis
The nonrandomized center selection might have induced a
bias if centers with higher compliance in the OAC therapy
implementation were involved in one or the other arm
Figure 2. Antithrombotic therapy before and after the evaluation
of the ANGELS (Anticoagulation Use Evaluation and Life Threatening Events Sentinels) of AF reports in the active intervention
arm. A therapy upgrade was observed in 24 patients, to OAC
in 22 and antiplatelet agents in 2. OAC indicates oral
anticoagulation.
without homogeneity. To exclude this bias, we evaluated the
OAC therapy implementation in the subgroup of patients who
were followed up for longer than 48 months in the ANGELS
of AF centers before ANGELS of AF project implementation
in the centers In 160 of these patients, 59.4% were on OAC
therapy at 48 months, a value much closer to the 56.8% in the
usual care control arm than to the 72.6% in the reporting arm.
The difference between 59.4% and 72.6% suggests, through a
comparison within the same group of centers, the possibility
of OAC therapy optimization.
Discussion
The presented results demonstrate that a medical care program may improve OAC implementation in standard medical
practice by supplying accurate and continuous information
about stroke risk factors, AF occurrence, and burden. We also
provide real-world data on thromboembolic events among
patients with ICDs and their association with stroke risk
scores and antithrombotic therapy.
OAC therapy implementation increased in both the arms of
the project. In the usual care control arm, the percentage of
indicated patients who were on OAC therapy was 46.9% at
baseline and increased to 56.8% at last follow-up. In the
active intervention arm, it was at 46.1% at baseline and
increased to 69% before the report was provided. This
increase may possibly be explained by the fact that device
diagnostics make it possible to better detect AF occurrence
and exactly define AF burden and type, whether paroxysmal
or persistent. Awareness of physicians participating to the
ANGELS of AF project is also a factor.
In the active intervention arm, the implementation of a
reporting system further improved OAC uptake and guideline
adherence to OAC therapy; in fact, anticoagulation therapy
was upgraded in 10.5% of patients after evaluation of the
ANGELS of AF reports. The net change in OAC implementation between the active intervention arm and the control
arm was 15.8%, which represented a statistically significant
change from 56.8% OAC implementation in the control arm
to 72.6% in the active intervention arm. This result is
clinically noteworthy in view of other dedicated program
efforts aimed at exploring and improving adherence to
recommendations for antithrombotic therapy in AF that
reported either no increase in warfarin prescription for AF in
heart failure at 2 and 3 years15,16 or an 11% increase in
warfarin prescription in the specific setting of in-hospital
management of stroke.17
The present results complement other observational studies
performed in non-ICD populations.15,16,18 –21 Of note, 82% of
the patients in the present research experienced heart failure.
Piccini et al15 found that from 2005 to 2007, the rate of OAC
use among patients with AF hospitalized for heart failure was
⬇60% to 65%. The IMPROVE HF (Registry to Improve the
Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting) study16 was performed to enhance quality of
care of patients with heart failure by facilitating adoption of
evidence-based guideline-recommended therapies. This
showed a significant improvement in 6 of 7 quality measures
at 12 and 24 months, especially, in the use of angiotensinconverting enzyme inhibitors, ␤-blockers, aldosterone antag-
Boriani et al
Improving Oral Anticoagulation Use in ICD Patients
5
Figure 3. Percentage of patients taking
antiplatelet agents, on oral anticoagulation therapy, or receiving at least 1 of
these 2 antithrombotic therapies as a
function of the observation period in the
active intervention arm and usual care
control arm.
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onists, cardiac resynchronization therapy, and ICD therapy,
but failed to improve the compliance for OAC therapy. The
percentage of indicated patients who were on OAC therapy
was 69% at baseline, and this remained stable during the
entire study follow-up period. In a study by Nieuwlaat et al19
among patients with AF and a high risk for stroke, antithromTable 2. Annual Rate of Stroke, TIA and Embolic Events as a
Function of CHADS2 in 1174 Patients With a History of AF or a
New-Onset AF
CHADS2
Patients
0
37
1
242
2
3
ⱖ4
436
329
130
Antithrombotic
Therapy
Total
Follow-Up, y
Patients
With
Events
Annual Rate
of Patients
With Event,
per 100
Patient-y
102
0
All
743
3
0
0.40
OAC
369
1
0.27
APA
185
1
0.54
Null
189
1
0.53
All
1202
7
0.58
OAC
565
1
0.18
APA
347
3
0.86
Null
290
3
1.03
All
838
8
0.95
OAC
428
4
0.93
APA
265
4
1.51
Null
145
0
0
All
275
4
1.45
OAC
137
3
2.19
APA
84
0
0
1.86
Null
54
1
All
3160
22
0.70
All
OAC
1530
9
0.59
All
APA
907
8
0.88
All
Null
723
5
0.69
All
1174
The number of patients for each antithrombotic therapy changed during the
observation period because of changes in the administered drug and, thus, is
not shown. The total follow-up period assigned to each antithrombotic therapy
is calculated while taking into account the actual therapy taken by the patient
and, therefore, the drug changes.
OAC indicates oral anticoagulation; APA, antiplatelet; Null, no antithrombotic
therapy.
botic treatment was consistent with the guidelines in 61% of
patients, and importantly, guideline nonadherence was associated with a higher risk of thromboembolism.
The ANGELS of AF project suggests that the implementation of a quality-of-care improvement intervention enhances OAC therapy compliance and reinforces the message
of the IMPROVE HF trial,16 which failed to enhance OAC
compliance. In the specific field of OAC treatment, the
present findings indicate that education and benchmark reporting should be integrated with patient-specific reports
about stroke risk factors and AF characteristics (occurrence,
temporal trends, and burden) as continuously monitored by
ICD diagnostics.
Gaps, variations, and disparities in the use of evidencebased, guideline-recommended therapies for AF in inpatient
and outpatient care settings are well documented; in particular, an important underuse of OAC therapy has been shown in
numerous studies evaluating clinical practice.4 – 6 As a result,
many patients with AF may experience embolic events, such
as strokes or TIAs, that might have been prevented. The
present project shows that hospital-based performance improvement programs may enhance quality of care in patients
with AF. In particular, in patients with ICDs, reliable and
continuous AF diagnostics may be exploited to supply physicians with useful reports about AF occurrence. Such a
reporting system may be of paramount importance because
studies have indicated that the majority of AF episodes are
asymptomatic, including many episodes of clinically significant duration.11 The identification of asymptomatic AF is of
primary importance for guiding OAC therapy in patients with
clinical risk factors, given that the risk for ischemic stroke is
similar in patients with intermittent and sustained AF.21
Patients with infrequent paroxysms of AF are the most
difficult to identify with intermittent monitoring and face a
significant stroke risk in the absence of appropriate OAC
therapy.18 Indeed, treatment guidelines recommend that we
should not consider the clinical AF subtype when deciding on
OAC.3
Today, device data can be sent from the patient’s home
through a telephone or Internet connection; therefore, physicians can have remote access to diagnostics. Clinical data
similarly may be accessed through the Intranet or Internet
using connectivity applications. The findings of the ANGELS
of AF project may serve as a model for future performance
improvement programs that link device and clinical data to
6
Circ Cardiovasc Qual Outcomes
March 2012
data warehouses fed by telemedicine and connectivity systems. Projects aiming to improve OAC use are warranted
because they may improve patient survival and quality of life
and reduce disability and hospital and social resource utilization. Furthermore, new OACs that reduce hemorrhagic
risk22,23 may reduce the barriers and the concerns for instituting anticoagulation, also facilitating the optimization of
patient management.
Cerebrovascular Events and Systemic Emboli:
Relationship With AF and CHADS2
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In the present population of patients with AF, the annual rate
of stroke, TIA, and embolic events was 0.7 per 100 patientyears, and an increasing trend as a function of CHADS2 score
(from 0.4 per 100 patient-years for a CHADS2 score of 1 to
1.45 per 100 patient-years for a CHADS2 score of ⱖ4) was
found (Table 2). Low rates of cerebrovascular events and
systemic emboli in patients with ICDs have been previously
shown, as in the TRENDS study,12 which estimated an annual
rate of 1.2 per 100 patient-years. The analysis of the incidence
of thromboembolic events should also consider that this 46%
of the patients were under treatment with OACs as a result of
current practice guidelines.
The temporal relationship of device-detected AF and
stroke, TIA, or embolic events showed that 64% of patients
had AF in any period preceding a thromboembolic event,
33% of patients had AF in the 30 days preceding a thromboembolic event, and 15% of patients had AF during thromboembolic events. Comparing recent findings by Daoud et al24
of 50%, 27.5%, and 15%, respectively, and the present
percentages confirms that AF has a causal relationship with
thromboembolic events, with a rate similar to that reported in
other studies.14,24 –27
Limitations
This research is limited by its nonrandomized observational
design. Nonetheless, we report unique, to our knowledge,
real-world data in a large cohort of patients with ICDs in
whom asymptomatic AF episodes may develop. The main
objective of the project was to implement a strategy for
improvement of OAC therapy; therefore, we did not design
the project to be powered to show the impact of the program
on the incidence of thromboembolic end points. Our estimation of embolic events rates may also be open to underreporting of clinical outcomes and some limitations in the ascertainment of causes of death.
The amount of AF burden, as detected by the ICDs, that
conveys a substantial risk of stroke has been the object of
debate.28 In this project, we adopted the cutoff of 6 hours, but
in the future, lower cutoffs may be used on the basis of new
data,29 also taking into account the extent of burden in
relationship with CHADS2 score; the increase in stroke risk is
achieved with a lower AF burden in patients at higher risk on
the basis of CHADS2.11,30 We did not collect baseline
information about mitral stenosis, cardiac thrombus, mechanical heart valve, blood pressure, or time from previous stroke
or TIA; therefore, we could not study these variables as stroke
predictors. We did not collect information about international
normalized ratio values and the time in therapeutic range for
patients who were anticoagulated. Finally, reasons for nonuse
of OAC therapy, such as contraindications or adverse events,
may not have been completely documented.
Conclusions
The ANGELS of AF project demonstrates the possibility of
improving OAC use in accordance with available guidelines
for stroke risk reduction in AF by supplying attending
physicians with reports about patient risk factors and AF
information from continuous device monitoring.
Acknowledgments
We thank Giorgia D’Ippolito for her technical support in the
management of data.
Sources of Funding
The research was performed in the framework of a medical care
project sponsored by Medtronic Italia, an affiliate of Medtronic Inc.
Disclosures
Dr Santini receives research grant support from Medtronic, St. Jude
Medical, and Biotronik and honoraria from Medtronic and Bayer;
has a speakers’ bureau appointment with MSD, Medtronic, St. Jude
Medical, and AstraZeneca; and has an advisory board relationship
with Boehringer Ingelheim. Dr Gasparini has an advisory board
relationship with Boston Scientific. Dr Proclemer receives research
grant support and has an advisory board relationship with Medtronic.
Dr Landolina has a speakers’ bureau appointment with St. Jude
Medical, Medtronic, and Boston Scientific and an advisory board
relationship with St. Jude Medical and Medtronic. Dr Padeletti
receives research grant support and an advisory board grant from
Medtronic. Dr Capucci has a speakers’ bureau appointment with St.
Jude Medical and Boston Scientific. Dr Ricci receives research grant
support from Medtronic, St. Jude Medical, and Biotronik and is a
consultant for Medtronic. M. Vimercati and Dr Grammatico are
employees of Medtronic Italia, an affiliate of Medtronic Inc. Dr Lip
has received funding for research, educational symposia, consultancy, and lecturing from different manufacturers, including Merck,
AstraZeneca, Boehringer Ingelheim, Bayer, BMS/Pfizer, Astellas,
Daiichi, Portola, Sanofi-Aventis, and Biotronik. The other authors
report no conflicts.
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Improving Thromboprophylaxis Using Atrial Fibrillation Diagnostic Capabilities in
Implantable Cardioverter-Defibrillators: The Multicentre Italian ANGELS of AF Project
Giuseppe Boriani, Massimo Santini, Maurizio Lunati, Maurizio Gasparini, Alessandro
Proclemer, Maurizio Landolina, Luigi Padeletti, Giovanni Luca Botto, Alessandro Capucci,
Stefano Bianchi, Mauro Biffi, Renato Pietro Ricci, Marco Vimercati, Andrea Grammatico,
Gregory Y.H. Lip and on behalf of the Italian ClinicalService Project
on behalf of the Italian ClinicalService Project
Circ Cardiovasc Qual Outcomes. published online February 28, 2012;
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