Comparing mortality in patients with atrial fibrillation who are receiving a direct-acting oral anticoagulant or warfarin: A meta-analysis of randomized trials

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 followup: 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). Conclusion: 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.