BackgroundIn 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.MethodsA meta-analysis was performed on phase3 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 revman5.2 and comprehensive meta analysis software version2. The results were presented as risk ratios (RRs), absolute risk reduction (ARR), and number-needed-to-treat (NNT).ResultsA total of 71683 patients were included in this meta-analysis from four randomized controlled trials (median patient follow-up: 1.8-2.8years) that compared a DOAC with warfarin for stroke prevention in AF. As compared with warfarin, DOACs significantly reduced all-cause mortality (RR0.89, 95% confidence interval [CI]0.85-0.94; ARR0.76%, 95%CI0.39-1.13%; NNT=132), vascular mortality (RR0.88, 95%CI0.82-0.94; ARR0.53%, 95%CI0.23-0.83%; NNT=189), and bleeding mortality (RR0.54, 95%CI0.44-0.67; ARR0.32%, 95%CI0.21-0.43%; NNT=313).ConclusionAs 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.