1. Real-World Comparative Effectiveness
and Safety of Rivaroxaban and Warfarin
in Nonvalvular Atrial Fibrillation Patients
François Laliberté1; Michel Cloutier1; Winnie W. Nelson2; Craig I.
Coleman3; Dominic Pilon1; CV Damaraju2; Jeffrey R. Schein2; Patrick
Lefebvre1
1Analysis
Group, Inc., Boston, MA;
2Janssen Scientific Affairs, LLC, Raritan, NJ;
3Univ of Connecticut & Hartford Hosp, Hartford, CT;
AHA Scientific Session, November 16-20, 2013, Dallas, TX
1

2. Disclosures
● Financial support for the research was provided in whole by Janssen
Scientific Affairs, LLC (JSA)
● François Laliberté, Michel Cloutier, Dominic Pilon, and Patrick
Lefebvre are employees of Analysis Group Inc., a consulting company
that has received research grants from JSA
● Craig I. Coleman is a Professor at University of Connecticut School of
Pharmacy and Co-Director of the University of Connecticut/Hartford
Hospital Evidence-Based Practice Center. He has received research
grants from JSA and serves as a member of Janssen speaker bureau
● Winnie W. Nelson, CV Damaraju, and Jeffrey R. Schein are
employees of JSA and stockholders of Johnson & Johnson
2

3. Background
● Chronic anticoagulants are regularly used in the prevention of
stroke in patients with nonvalvular atrial fibrillation (NVAF)
● Until recently, warfarin and other oral vitamin-K antagonist (VKA)
anticoagulants were the only oral anticoagulants available for
stroke prevention
● Target-specific oral anticoagulants (e.g., rivaroxaban, dabigatran,
apixaban) were approved for the prevention of stroke and
systemic embolism in patients with NVAF
● The ROCKET-AF trial has demonstrated that rivaroxaban is
effective in reducing the risk of stroke and systemic embolism
● The objective of this study was to assess real-world effectiveness,
safety, and patients’ continued use of rivaroxaban and warfarin
(i.e. persistence)
3

4. Methods - Data Source
Symphony Health Solutions Patient Transactional Datasets from
May 2011 to July 2012
• Longitudinal patient data source with data from adjudicated
medical and pharmacy claims
• Contains approximately 4.8 billion prescription claims across
the U.S. for all payment types (e.g., commercials plans,
Medicare Part D, assistance programs, and Medicaid)
• Linked with claims from hospital and physician practices for
over 190 million patients
• Data de-identified in compliance with HIPAA
4

5. Methods - Study Sample
Inclusion criteria
• Newly initiated on rivaroxaban or warfarin (at least 180 days of
clinical activity prior to the index date)
• Age greater than or equal to 18 years
• CHADS2 score ≥1 during the 180-day baseline period
• ≥2 AF diagnoses (ICD-9-CM: 427.31) during baseline or follow-up
Exclusion criteria
• Patients with the following conditions:
─ Valvular involvement
─ Pregnancy
─ Malignant cancer
─ Transient causes of AF
5

6. Methods - Study Design
● Retrospective matched-cohort design ensured groups were well
balanced at baseline
● Each rivaroxaban user matched with up to 4 warfarin users based
on propensity score
● The observation period spanned from the index date until:
− End of clinical activity, or
− End of data availability
● In addition, for clinical endpoints, observation period is further
restricted to
− Switch of anticoagulant, or
− 14 days after treatment discontinuation
6

7. Methods - Study Endpoints
● Safety
• Major bleeding
• Gastrointestinal (GI) bleeding
● Effectiveness*
• Composite stroke and systemic embolism
─ Ischemic stroke
─ Hemorrhagic stroke
─ Systemic embolism
• Venous thromboembolism (VTE)
─ Deep vein thrombosis (DVT) only
─ Pulmonary embolism (PE) with or without DVT
● Medication persistence to the index therapy
* Events identified during a hospitalization or emergency department visit
7

8. Statistical Methods
● Descriptive statistics to summarize the patient characteristics and
compared using standardized differences
● Cox proportional hazard regressions to calculate hazard ratios
(HRs) of bleeding (major and GI), composite stroke and systemic
embolism, and VTE events between groups
● Kaplan-Meier estimates and HRs to compare the time to non-
persistence
− Non-persistence defined as having a refill gap of 60 days or larger
8

9. Patients Characteristics
Matched Cohort
Characteristics
Warfarin
(N=3,654)
Demographics
Age, years, mean (SD)
Gender, female, n (%)
Quan-Charlson comorbidity index
CHADS2 score
Selected baseline risk factors , n(%)
Age > 60
Prior stroke
Hypertension
Hyperlipidemia
Diabetes
Heart failure
Rivaroxaban
(N=13,876)
Standardized
Difference
73.3 (8.4)
1,865 (51.0%)
1.1 (1.3)
2.0 (1.0)
73.7 (8.3)
7,159 (51.6%)
1.2 (1.4)
2.0 (1.0)
4.6%
1.1%
3.3%
2.2%
3,313 (90.7%)
357 (9.8%)
2,626 (71.9%)
1,616 (44.2%)
919 (25.2%)
716 (19.6%)
12,681 (91.4%)
1434 (9.8%)
9,761 (70.3%)
6,032 (43.5%)
3,599 (25.9%)
2,858 (20.6%)
2.5%
3.4%
3.4%
1.5%
1.8%
2.5%
9

10. Hazard Ratios of Study Endpoints
Rivaroxaban vs. Warfarin
Hazard Ratios [95% CI]
Major bleeding
1.03 [0.68 - 1.56]
GI bleeding
Composite stroke and
systemic embolism†
Ischemic stroke†
1.26 [0.98 - 1.62]
Hemorrhagic stroke†
1.10 [0.12 - 9.86]
Systemic embolism†
0.78 [0.17 - 3.50]
DVT only†
0.55 [0.25 - 1.21]
PE with or without
DVT†
1.06 [0.40 - 2.80]
0.81 [0.58 - 1.15]
0.83 [0.59 - 1.18]
0
Rivaroxaban better
1
2
3
Warfarin better
†Event identified during a hospitalization or emergency department visit
10

11. % of patients persistent with treatment
Treatment Persistence
100%
HR = 0.66 (0.60-0.72), P<0.001
90%
85%
81%
80%
Warfarin User Cohort
Rivaroxaban User Cohort
70%
76%
68%
60%
0
30
60
90
120
Time to event (days)
150
180
11

12. Limitations
● Claims database may contain inaccuracies or omissions in coded
procedures, diagnoses, or pharmacy claims
● Propensity score matching only accounts for observable factors
● Despite matching, the observational nature of the analysis still
carries the possibility of confounding
● Study was conducted when rivaroxaban was first available; use
patterns may change over time
12

13. Conclusions
● This analysis suggests that rivaroxaban and warfarin do not
differ significantly in real-world rates of composite stroke and
systemic embolism, major bleeding, and GI bleeding
● Rivaroxaban was associated with a significantly higher
treatment persistence compared with warfarin
13