Scientific Publications by FDA Staff

Circulation 2015 Jan 13;131(2):157-64

Cardiovascular, bleeding, and mortality risks in elderly medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation.

Graham DJ, Reichman ME, Wernecke M, Zhang R, Southworth MR, Levenson M, Sheu TC, Mott K, Goulding MR, Houstoun M, MaCurdy TE, Worrall C, Kelman JA

BACKGROUND: -The comparative safety of dabigatran vs. warfarin for treatment of non-valvular atrial fibrillation (AF) in general practice settings has not been established. METHODS AND RESULTS: -We formed new-user cohorts of propensity score matched elderly patients enrolled in Medicare, who initiated dabigatran or warfarin for treatment of non-valvular AF between October 2010 and December 2012. Among 134,414 patients with 37,587 person-years of follow-up, there were 2,715 primary outcome events. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were ischemic stroke: 0.80 (0.67-0.96); intracranial hemorrhage: 0.34 (0.26-0.46); major gastrointestinal bleeding: 1.28 (1.14-1.44); acute myocardial infarction: 0.92 (0.78-1.08); and death: 0.86 (0.77-0.96). In the subgroup treated with dabigatran 75 mg twice daily, there was no difference in risk compared with warfarin for any outcome except intracranial hemorrhage, where dabigatran risk was reduced. Most patients treated with dabigatran 75 mg twice daily appeared not to have severe renal impairment, the intended population for this dose. In the dabigatran 150 mg twice daily subgroup, the magnitude of effect for each outcome was greater than in the combined-dose analysis. CONCLUSIONS: -In general practice settings, dabigatran was associated with reduced risk of ischemic stroke, intracranial hemorrhage, and death, and increased risk of major gastrointestinal hemorrhage compared with warfarin in elderly patients with non-valvular AF. These associations were most pronounced in patients treated with dabigatran 150 mg twice daily, whereas the association of 75 mg twice daily with study outcomes was indistinguishable from warfarin except for a lower risk of intracranial hemorrhage with dabigatran.