title: Cardiovascular, bleeding, and mortality risks in elderly Medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation.
abstract: BACKGROUND
  The comparative safety of dabigatran versus warfarin for treatment of nonvalvular atrial fibrillation in general practice settings has not been established.
  
  
  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.affiliation: 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.
authors.forename: David J
authors.initials: DJ
authors.lastname: Graham
authors.affiliation: 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.).
authors.forename: Marsha E
authors.initials: ME
authors.lastname: Reichman
authors.affiliation: 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.).
authors.forename: Michael
authors.initials: M
authors.lastname: Wernecke
authors.affiliation: 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.).
authors.forename: Rongmei
authors.initials: R
authors.lastname: Zhang
authors.affiliation: 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.).
authors.forename: Mary Ross
authors.initials: MR
authors.lastname: Southworth
authors.affiliation: 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.).
authors.forename: Mark
authors.initials: M
authors.lastname: Levenson
authors.affiliation: 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.).
authors.forename: Ting-Chang
authors.initials: TC
authors.lastname: Sheu
authors.affiliation: 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.).
authors.forename: Katrina
authors.initials: K
authors.lastname: Mott
authors.affiliation: 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.).
authors.forename: Margie R
authors.initials: MR
authors.lastname: Goulding
authors.affiliation: 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.).
authors.forename: Monika
authors.initials: M
authors.lastname: Houstoun
authors.affiliation: 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.).
authors.forename: Thomas E
authors.initials: TE
authors.lastname: MaCurdy
authors.affiliation: 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.).
authors.forename: Chris
authors.initials: C
authors.lastname: Worrall
authors.affiliation: 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.).
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kelman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015897:Comorbidity; D000069604:Dabigatran; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000453:epidemiology; D006278:Medicare / Q000706:statistics & numerical data*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012306:Risk; D012959:Socioeconomic Factors; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D016896:Treatment Outcome; D014481:United States; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*; D015091:beta-Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000889:Anti-Arrhythmia Agents; D000925:Anticoagulants; D001562:Benzimidazoles; D015091:beta-Alanine; D014859:Warfarin; D000069604:Dabigatran
keywords: anticoagulant; pharmacoepidemiology; safety; thrombin inhibitor; warfarin