Efficacy and Safety of Edoxaban in Nonvalvular Atrial Fibrillation: A Meta-analysis of Randomized Controlled Trials

Goals: Edoxaban is a potential alternative to warfarin for preventing thromboembolism in atrial fibrillation. However, the efficacy and safety, and the optimal regimen of edoxaban are still controversial. This study compared the efficacy and safety of edoxaban and warfarin in nonvalvular atrial fibrillation, and the effects of different edoxaban dosages. Methods: A systematic search for randomized controlled trials comparing edoxaban with warfarin in nonvalvular atrial fibrillation was conducted using PubMed, EMBASE, and the Cochrane Library databases. The main measures and outcomes included efficacy end points (thromboembolic events and all-cause mortality) and safety end points (all bleeding events, major bleeding events, clinically relevant nonmajor bleeding, and minor bleeding). Results: Four studies including 23,001 patients were included in the meta-analysis. Edoxaban was noninferior to warfarin for preventing stroke and systemic embolism (risk ratio [RR] = 1.00; 95% confidence interval [CI],.88-1.13; Z = .01; P = .99). In safety analyses, edoxaban was superior to warfarin in terms of major bleeding, clinically relevant nonmajor bleeding, and minor bleeding (all P < .00001). In terms of optimal dosing, 30 mg/day edoxaban had a significantly lower risk of all bleeding (RR = .79; 95% CI,.75-.83; Z = 9.07; P < .00001) than 60 mg/day, but was inferior at preventing stroke and systemic embolism (RR = 1.31; 95% CI, 1.13-1.51; Z = 3.56; P = .0004). Conclusions: Edoxaban was noninferior to warfarin in terms of efficacy and superior to warfarin in terms of safety. The benefits of edoxaban were related to the dose; efficacy was better at 60 mg/day, but there was lower risk of bleeding at 30 mg/day. (C) 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.