Assessment of the Effect of Target Specific Oral

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Assessment of the Effect of Target Specific Oral
UNC REX HEALTHCARE
Assessment of the Effect of Target Specific
Oral Anticoagulants for Treatment of Venous
Thromboembolism in Oncology Patients
Elizabeth Weddendorf, PharmD
PGY1 Pharmacy Practice Resident
UNC Rex Healthcare
Raleigh, NC
[email protected]
UNC REX HEALTHCARE
Disclosure Statement
Authors of this presentation have the following to disclose
concerning possible financial or personal relationships with
commercial entities that may have a direct or indirect interest in
the subject matter of this presentation.
• Resident
– Elizabeth C. Weddendorf, PharmD – nothing to disclose
• Co-Investigators
–
–
–
–
–
–
Rebecca Jones, PharmD, BCPS – nothing to disclose
Jeffrey Crane, MD – nothing to disclose
W. Russell Laundon, PharmD, MS, BCPS – nothing to disclose
Jared Peak, PharmD, BCACP, CPP – nothing to disclose
Madison Sasser, PharmD, BCPS – nothing to disclose
Wayne Smith, MD – nothing to disclose
UNC REX HEALTHCARE
UNC Rex Healthcare
660 bed community,
acute-care hospital
• Raleigh, NC
Outpatient oncology
clinics
• Raleigh, NC
• Wakefield
• Blue Ridge
• Lake Boone Trail
• Cary, NC
• Garner, NC
UNC REX HEALTHCARE
Background
• Venous thromboembolism (VTE) is a frequent complication in
patients with cancer
• Risk of VTE varies according to type of cancer
Type of Cancer
Ovarian, breast, lymphoma
Brain, colon, lung, pancreatic
Approximate Incidence (%)
10
20
• Risk of recurrence after a first episode of VTE is higher in
patients with cancer compared to those without cancer
Thromb Haemost.2002;87:1076-1077, Thromb Haemost.2002;87:575-579
Circulation.2003;107:I-17-I-2J, Clin Oncol. 2007; 25(1):70-761, Gynecol Oncol. 2007; 105(3):784-790
UNC REX HEALTHCARE
Background
Evidence Based Guidelines
American Society of Clinical
Oncology (ASCO)
National Cancer Comprehensive
Network (NCCN)
American College of Chest
Physicians (ACCP)
Recommendation for Prevention of
Recurrent VTE in Cancer
• Low molecular weight heparin (LMWH)
preferred for 3-6 months after initial VTE
event
• Vitamin K antagonists (VKAs) are considered
an acceptable alternative if LMWH is not
ideal
Trial
N
Comparison
CLOT
676
Daltaparin vs warfarin Significant recurrent VTE with warfarin
CATCH
900
Tinzaparin vs warfarin Significant reduction in symptomatic DVT
with LMWH
Ann Oncol. 2011 Sep;22 Suppl 6:vi85-92
ASCO. J Clin Oncol. 2013 Jun 10;31(17):2189-204
Conclusion
Lee AY, et al. JAMA. 2015;314:677-686
Lee AY, et al. NEJM. 2003;349:146-153
UNC REX HEALTHCARE
Background
LMWH
• Pros: stable PK and PD profile, few drug interactions
• Cons: daily subcutaneous injection for 3 to 6 months
VKAs
• Pros: oral route of administration often preferred
• Cons: frequent monitoring, complicated dosing
regimens, drug and food interactions, and difficulty
maintaining therapeutic INR
Ann Oncol. 2011 Sep;22 Suppl 6:vi85-92
ASCO. J Clin Oncol. 2013 Jun 10;31(17):2189-204
UNC REX HEALTHCARE
Background
• 2016 CHEST guidelines suggest target specific oral
anticoagulants (TSOACs) over warfarin for treatment of acute
DVT or PE in patients without cancer
• In patients with DVT or PE with cancer, LMWH is suggested
over VKAs and TSOACs
Trial
Medication
Cancer patients (%)
RE-COVER
Dabigatran vs. warfarin
EINSTEIN-DVT
EINSTEIN-PE
Rivaroxaban vs. enoxaparin + VKA
6.8
4.7
Hokusai-VTE
Edoxaban vs. VKA
9.2
AMPLIFY
Apixaban vs. enoxaparin + VKA
2.5
N Engl J Med. 2009 Dec 10; 361(24):2342-52, N Engl J Med. 2010 Dec 23; 363(26):2499510, N Engl J Med. 2012 Apr 5; 366(14):1287-97, N Engl J Med. 2013 Aug 29; 369(9):799808, N Engl J Med. 2013 Oct 10; 369(15):1406-15, CHEST 2016; 149(2):315-352
5
UNC REX HEALTHCARE
Background
• ASCO and NCCN guidelines currently do not recommend use
of target specific oral anticoagulants (TSOACs) for treatment
cancer-associated VTE
• TSOACs are an attractive option to treat VTE in oncology
patients
– Oral administration
– Fixed-dose regimen without routine monitoring
– Fewer drug and food interactions
• Some physicians have started prescribing TSOACs for
treatment of cancer-associated VTE
Ann Oncol. 2011 Sep;22 Suppl 6:vi85-92
ASCO. J Clin Oncol. 2013 Jun 10;31(17):2189-204
UNC REX HEALTHCARE
Purpose
To evaluate the recurrence of VTE in oncology
patients receiving TSOACs compared to those
receiving LMWH
UNC REX HEALTHCARE
Objectives
• Primary objective
– Rate of recurrence of VTE in patients taking a TSOAC
compared to those receiving LMWH
• Secondary objective
– Rate of major bleed
• A bleeding event causing a decrease in hemoglobin ≥ 2 g/dL
• Any bleeding event requiring transfusion of 2 or more units of
blood
• Any bleeding event occurring in a critical site (intracranial,
intraspinal, intraocular, retroperitoneal or pericardial area)
• Any bleeding event contributing to patient death
Journal of Thrombosis and Haemostasis, 3: 692–694
UNC REX HEALTHCARE
Methodology
Study Design
• IRB approved
• Single-center, retrospective, chart review
cohort study
• Patients were identified using ICD-9 and ICD10 codes
UNC REX HEALTHCARE
Methodology
Inclusion criteria
• ≥ 18 years old
• Diagnosis of active cancer that confers high risk of VTE
• Ovarian, brain, pancreatic, colon, breast, uterine, lung, and lymphoma
• Diagnosis of current DVT and/or PE
• Taking treatment dose of apixaban, dabigatran, rivaroxaban, edoxaban or
LMWH
• Treated at UNC Rex Hospital or outpatient oncology clinic between June
20, 2014 and December 1, 2016
Exclusion criteria
•
•
•
•
< 18 years old
Taking warfarin
Pregnancy
Current incarceration
UNC REX HEALTHCARE
Statistics
• Analysis were conducted with SAS version 9.3 (Copyright ©
2012 SAS Institute Inc.)
• Nominal variables were analyzed using a Chi-square test
• Series of odds ratios (ORs) and corresponding 95%
confidence intervals were analyzed
• No adjustments were made for multiple comparisons
UNC REX HEALTHCARE
Enrollment
230 patients assessed for
eligibility
79 had orders for TSOAC
14 patients excluded
•
•
•
8 cancer diagnosis not
included
5 no active cancer
diagnosis
1 incarceration
65 patients included in TSOAC
analysis
151 had orders for LMWH
80 patients excluded
• 39 not treatment dose
• 16 no current VTE
diagnosis
• 9 did not receive LMWH
• 8 taking warfarin
• 5 no active cancer
diagnosis
• 3 cancer diagnosis not
included
71 patients included in LMWH
analysis
UNC REX HEALTHCARE
Patient Characteristics
Characteristic
All Patients
TSOAC
(n = 65)
LMWH
(n = 71)
64.5 (±12.9)
64 (±9.4)
Female sex – no. (%)
41 (63.1)
40 (56.3)
Male sex – no. (%)
24 (36.9)
31 (43.7)
Weight – Mean - kg
81.2
78.8
≥ 50 ml/min
56 (86.2)
61 (85.9)
49 – 30 ml/min
7 (10.7)
9 (12.7)
< 30 ml/min
2 (3.1)
1 (1.4)
Age – Mean (±SD) – year
Creatinine Clearance – no. (%)
UNC REX HEALTHCARE
Patient Characteristics
Characteristic
Cancer Type – no. (%)
Lung
Breast
Colon
Pancreatic
Ovarian
Lymphoma
Uterine
Brain
Chemotherapy
Yes – no. (%)
All Patients
TSOAC
(n = 65)
LMWH
(n = 71)
16 (24.6)
19 (29.3)
12 (18.5)
6 (9.2)
3 (4.6)
5 (7.7)
3 (4.6)
1 (1.5)
25 (35.2)
8 (11.3)
9 (12.7)
15 (21.1)
7 (9.9)
4 (5.6)
2 (2.8)
1 (1.4)
33 (50.7)
36 (50.7)
UNC REX HEALTHCARE
Patient Characteristics
Characteristic
Anticoagulant – no. (%)
enoxaparin
edoxaban
dabigatran
rivaroxaban
apixaban
All Patients
TSOAC
(n = 65)
LMWH
(n = 71)
0
1 (1.5)
6 (9.2)
49 (75.4)
9 (13.9)
71 (100)
0
0
0
0
UNC REX HEALTHCARE
Results
Outcome
All Patients
TSOAC
(n = 65)
LMWH
(n = 71)
Overall P-value
Odds Ratio (95% CI)
Primary efficacy outcome:
recurrent VTE
No. (%)
4 (6.2)
7 (9.9)
p = 0.4286
0.60 (0.17 – 2.15)
Secondary safety outcome:
major bleed
No. (%)
5 (7.7)
12 (16.9)
p = 0.1048
0.41 (0.14 – 1.24)
UNC REX HEALTHCARE
Discussion
• Incidence of recurrent VTE was not statistically
significant in the TSOAC group compared to current
standard of care with LMWH
• There were more occurrences of major bleed observed
in the LMWH group, but this was not found to be
statistically significant
• Limitations
–
–
–
–
–
Retrospective
Coding errors
Incomplete medical records
Propensity for type 2 error
Selection bias
UNC REX HEALTHCARE
Discussion
These results suggest TSOACs may be a reasonable
option for the treatment of VTE in some patients
with cancer
• Due to the retrospective design and limited sample
size of this study, further studies are needed on the
topic
UNC REX HEALTHCARE
Self Assessment Question
Is the use of target specific oral anticoagulants efficacious
for the treatment of venous thromboembolism within this
patient population?
Based on the results of this study, the use of target specific
oral anticoagulants appear to be efficacious for the treatment
of VTE within this patient population
UNC REX HEALTHCARE
Assessment of the Effect of Target Specific
Oral Anticoagulants for Treatment of Venous
Thromboembolism in Oncology Patients
Elizabeth Weddendorf, PharmD
PGY1 Pharmacy Practice Resident
UNC Rex Healthcare
Raleigh, NC
[email protected]

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