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

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 abstracts and , 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; I-2 = 0%) in patients taking DOACs and 11.04% (95% CI, 9.16-13.07; I-2 = 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; I-2 = 36.5%). When compared with warfarin, DOACs were associated with significant reductions in fatal bleeding (RR, 0.53; 95% CI, 0.43-0.64; I-2 = 0%), cardiovascular mortality (RR, 0.88; 95% CI, 0.82-0.94; I-2 = 0%) and all-cause mortality (RR, 0.91; 95% CI, 0.87-0.96; I-2 = 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.