David J Graham1, Marsha E Reichman2, Michael Wernecke2, Rongmei Zhang2, Mary Ross Southworth2, Mark Levenson2, Ting-Chang Sheu2, Katrina Mott2, Margie R Goulding2, Monika Houstoun2, Thomas E MaCurdy2, Chris Worrall2, Jeffrey A Kelman2. 1. From the Office of Surveillance and Epidemiology (D.J.G., M.E.R., K.M., M.R.G., M.H.), Office of Biostatistics (R.Z., M.L.), and Office of New Drugs (M.R.S.), Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD; Acumen LLC, Burlingame, CA (M.W., T.S., T.E.M.); Department of Economics, Stanford University, Stanford, CA (T.E.M.); and Centers for Medicare & Medicaid Services, Washington, DC (C.W., J.A.K.). david.graham1@fda.hhs.gov. 2. From the Office of Surveillance and Epidemiology (D.J.G., M.E.R., K.M., M.R.G., M.H.), Office of Biostatistics (R.Z., M.L.), and Office of New Drugs (M.R.S.), Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD; Acumen LLC, Burlingame, CA (M.W., T.S., T.E.M.); Department of Economics, Stanford University, Stanford, CA (T.E.M.); and Centers for Medicare & Medicaid Services, Washington, DC (C.W., J.A.K.).
Abstract
BACKGROUND: The comparative safety of dabigatran versus warfarin for treatment of nonvalvular atrial fibrillation 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 nonvalvular atrial fibrillation between October 2010 and December 2012. Among 134 414 patients with 37 587 person-years of follow-up, there were 2715 primary outcome events. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were as follows: 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, in which case 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 nonvalvular atrial fibrillation. 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.
BACKGROUND: The comparative safety of dabigatran versus warfarin for treatment of nonvalvular atrial fibrillation 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 nonvalvular atrial fibrillation between October 2010 and December 2012. Among 134 414 patients with 37 587 person-years of follow-up, there were 2715 primary outcome events. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were as follows: 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, in which case 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 nonvalvular atrial fibrillation. 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.
Authors: Ghanshyam Palamaner Subash Shantha; Prashant D Bhave; Saket Girotra; Denice Hodgson-Zingman; Alexander Mazur; Michael Giudici; Elizabeth Chrischilles; Mary S Vaughan Sarrazin Journal: Circ Cardiovasc Qual Outcomes Date: 2017-04
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Authors: Mariam Ujeyl; Ingrid Köster; Hans Wille; Thomas Stammschulte; Rebecca Hein; Sebastian Harder; Ursula Gundert-Remy; Julian Bleek; Peter Ihle; Helmut Schröder; Gerhard Schillinger; Anette Zawinell; Ingrid Schubert Journal: Eur J Clin Pharmacol Date: 2018-06-16 Impact factor: 2.953