title: Comparing mortality in patients with atrial fibrillation who are receiving a direct-acting oral anticoagulant or warfarin: a meta-analysis of randomized trials.
abstract: BACKGROUND
  In patients with non-valvular atrial fibrillation (AF), direct-acting oral anticoagulants (DOACs) are at least non-inferior to warfarin for the prevention of stroke and systemic embolism. The main objective of this study was to obtain reliable and precise estimates for all-cause mortality, vascular mortality and bleeding mortality in patients with AF receiving a DOAC or warfarin for stroke prevention.
  
  
  METHODS
  A meta-analysis was performed on phase 3 randomized trials that compared a DOAC with warfarin for stroke prevention in AF. Published data were pooled by use of the DerSimonian random-effect model, with revman 5.2 and comprehensive meta analysis software version 2. The results were presented as risk ratios (RRs), absolute risk reduction (ARR), and number-needed-to-treat (NNT).
  
  
  RESULTS
  A total of 71 683 patients were included in this meta-analysis from four randomized controlled trials (median patient follow-up: 1.8-2.8 years) that compared a DOAC with warfarin for stroke prevention in AF. As compared with warfarin, DOACs significantly reduced all-cause mortality (RR 0.89, 95% confidence interval [CI] 0.85-0.94; ARR 0.76%, 95% CI 0.39-1.13%; NNT = 132), vascular mortality (RR 0.88, 95% CI 0.82-0.94; ARR 0.53%, 95% CI 0.23-0.83%; NNT = 189), and bleeding mortality (RR 0.54, 95% CI 0.44-0.67; ARR 0.32%, 95% CI 0.21-0.43%; NNT = 313).
  
  
  CONCLUSIONS
  As compared with warfarin therapy for stroke prevention in patients with AF, DOACs significantly reduce all-cause mortality, vascular mortality, and bleeding mortality. This mortality benefit appears to be driven by the reduction in vascular-related and bleeding-related mortality, which, in turn, may be related to the reduction in intracranial bleeding.
authors.affiliation: Department of Medicine, National University of Ireland Galway (NUIG), Galway, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Liew
authors.forename: M
authors.initials: M
authors.lastname: O'Donnell
authors.forename: J
authors.initials: J
authors.lastname: Douketis
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality*; D017326:Clinical Trials, Phase III as Topic; D004617:Embolism / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D020521:Stroke / Q000188:drug therapy / Q000517:prevention & control; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: anticoagulants; atrial fibrillation; hemorrhage; mortality; warfarin