Mortality outcomes in patients receiving direct oral anticoagulants: a systematic review and meta‐analysis of randomized controlled trials

Summary Background Direct oral anticoagulants (DOACs) are widely used as an alternative for warfarin. However, the impact of DOACs on mortality outcomes compared with warfarin remains unclear. Objective To estimate the mortality outcomes in patients treated with DOACs vs. warfarin (or another vitamin K antagonist). Methods MEDLINE, EMBASE and CENTRAL databases (inception to September 2014), conference s and www.clinicaltrials.gov, were searched, without language restriction. Studies were selected if there were phase III, randomized trials comparing DOACs with warfarin in patients with non‐valvular atrial fibrillation or venous thromboembolism. Results Thirteen randomized controlled trials involving 102 707 adult patients were included in the analysis. The case‐fatality rate of major bleeding was 7.57% (95% CI, 6.53–8.68; I2 = 0%) in patients taking DOACs and 11.04% (95% CI, 9.16–13.07; I2 = 33.3%) in patients taking warfarin. The rate of fatal bleeding in adult patients receiving DOACs was 0.16 per 100 patient‐years (95% CI, 0.12–0.20; I2 = 36.5%). When compared with warfarin, DOACs were associated with significant reductions in fatal bleeding (RR, 0.53; 95% CI, 0.43–0.64; I2 = 0%), cardiovascular mortality (RR, 0.88; 95% CI, 0.82–0.94; I2 = 0%) and all‐cause mortality (RR, 0.91; 95% CI, 0.87–0.96; I2 = 0%). Conclusions The use of DOACs compared with warfarin is associated with a lower rate of fatal bleeding, case‐fatality rate of major bleeding, cardiovascular mortality and all‐cause mortality.