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Original Investigation
November 2016

Stroke, Bleeding, and Mortality Risks in Elderly Medicare Beneficiaries Treated With Dabigatran or Rivaroxaban for Nonvalvular Atrial Fibrillation

Author Affiliations
  • 1Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland
  • 2Acumen LLC, Burlingame, California
  • 3Office of Biostatistics, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland
  • 4Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland
  • 5Department of Economics, Stanford University, Stanford, California
  • 6Centers for Medicare & Medicaid Services, Washington, DC
JAMA Intern Med. 2016;176(11):1662-1671. doi:10.1001/jamainternmed.2016.5954
Key Points

Question  How does rivaroxaban compare with dabigatran for stroke, bleeding, and mortality risks in patients with atrial fibrillation?

Findings  In a new-user cohort study of 118 891 patients, rivaroxaban treatment was associated with significantly increased intracranial hemorrhage and major extracranial bleeding, including major gastrointestinal bleeding, and nonsignificantly reduced risk of thromboembolic stroke and increased risk of mortality. The absolute increase in intracranial hemorrhage with rivaroxaban treatment exceeded its reduced rate of thromboembolic stroke.

Meaning  In this observational study, rivaroxaban use was associated with increased intracranial and major extracranial bleeding events compared with dabigatran use.

Abstract

Importance  Dabigatran and rivaroxaban are non–vitamin K oral anticoagulants approved for stroke prevention in patients with nonvalvular atrial fibrillation (AF). There are no randomized head-to-head comparisons of these drugs for stroke, bleeding, or mortality outcomes.

Objective  To compare risks of thromboembolic stroke, intracranial hemorrhage (ICH), major extracranial bleeding including major gastrointestinal bleeding, and mortality in patients with nonvalvular AF who initiated dabigatran or rivaroxaban treatment for stroke prevention.

Design, Setting, and Participants  Retrospective new-user cohort study of 118 891 patients with nonvalvular AF who were 65 years or older, enrolled in fee-for-service Medicare, and who initiated treatment with dabigatran or rivaroxaban from November 4, 2011, through June 30, 2014. Differences in baseline characteristics were adjusted using stabilized inverse probability of treatment weights based on propensity scores. The data analysis was performed from May 7, 2015, through June 30, 2016.

Exposures  Dabigatran, 150 mg, twice daily; rivaroxaban, 20 mg, once daily.

Main Outcomes and Measures  Adjusted hazard ratios (HRs) for the primary outcomes of thromboembolic stroke, ICH, major extracranial bleeding including major gastrointestinal bleeding, and mortality, with dabigatran as reference. Adjusted incidence rate differences (AIRDs) were also estimated.

Results  A total of 52 240 dabigatran-treated and 66 651 rivaroxaban-treated patients (47% female) contributed 15 524 and 20 199 person-years of on-treatment follow-up, respectively, during which 2537 primary outcome events occurred. Rivaroxaban use was associated with a statistically nonsignificant reduction in thromboembolic stroke (HR, 0.81; 95% CI, 0.65-1.01; P = .07; AIRD = 1.8 fewer cases/1000 person-years), statistically significant increases in ICH (HR, 1.65; 95% CI, 1.20-2.26; P = .002; AIRD = 2.3 excess cases/1000 person-years) and major extracranial bleeding (HR, 1.48; 95% CI, 1.32-1.67; P < .001; AIRD = 13.0 excess cases/1000 person-years), including major gastrointestinal bleeding (HR, 1.40; 95% CI, 1.23-1.59; P < .001; AIRD = 9.4 excess cases/1000 person-years), and with a statistically nonsignificant increase in mortality (HR, 1.15; 95% CI, 1.00-1.32; P = .051; AIRD = 3.1 excess cases/1000 person-years). In patients 75 years or older or with CHADS2 score greater than 2, rivaroxaban use was associated with significantly increased mortality compared with dabigatran use. The excess rate of ICH with rivaroxaban use exceeded its reduced rate of thromboembolic stroke.

Conclusions and Relevance  Treatment with rivaroxaban 20 mg once daily was associated with statistically significant increases in ICH and major extracranial bleeding, including major gastrointestinal bleeding, compared with dabigatran 150 mg twice daily.

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