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



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.



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.



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



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.



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.



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.
Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
David J
DJ
Graham
Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
Marsha E
ME
Reichman
Acumen LLC, Burlingame, California.
Michael
M
Wernecke
Office of Biostatistics, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
Ya-Hui
YH
Hsueh
Office of Biostatistics, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
Rima
R
Izem
Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
Mary Ross
MR
Southworth
Acumen LLC, Burlingame, California.
Yuqin
Y
Wei
Acumen LLC, Burlingame, California.
Jiemin
J
Liao
Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
Margie R
MR
Goulding
Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
Katrina
K
Mott
Acumen LLC, Burlingame, California.
Yoganand
Y
Chillarige
Acumen LLC, Burlingame, California5Department of Economics, Stanford University, Stanford, California.
Thomas E
TE
MaCurdy
Centers for Medicare & Medicaid Services, Washington, DC.
Chris
C
Worrall
Centers for Medicare & Medicaid Services, Washington, DC.
Jeffrey A
JA
Kelman
D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality; D015331:Cohort Studies; D000069604:Dabigatran / Q000627:therapeutic use*; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000517:prevention & control*; D006349:Heart Valve Diseases / Q000188:drug therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D006278:Medicare; D012189:Retrospective Studies; D012307:Risk Factors; D000069552:Rivaroxaban / Q000627:therapeutic use*; D020521:Stroke / Q000517:prevention & control*; D016896:Treatment Outcome; D014481:United States
D000991:Antithrombins; D065427:Factor Xa Inhibitors; D000069552:Rivaroxaban; D000069604:Dabigatran