Systematic review and network meta-analysis of the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants among patients with nonvalvular atrial fibrillation and CHADS(2) score ⩾ 2

BACKGROUND: The nonvitamin K antagonist oral anticoagulants pivotal clinical trials for stroke prevention in atrial fibrillation have important differences in trial designs and baseline patient characteristics. OBJECTIVE: We sought to evaluate the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants in the management of stroke prevention in atrial fibrillation by adjusting for differences in baseline stroke risk and the length of follow-up among the four phase 3 randomized controlled trials. METHODS: We conducted a systematic literature review of randomized controlled trials evaluating the nonvitamin K antagonist oral anticoagulants for stroke prevention in atrial fibrillation and performed a network meta-analysis using data from ENGAGE AF-TIMI 48, RE-LY, ROCKET-AF, and ARISTOTLE, with warfarin as a common comparator. To adjust for between-trial differences in CHADS(2) score and length of follow-up, annualized event rates among patients with CHADS(2) score ⩾ 2 were analyzed using a mixed Poisson’s regression model. RESULTS: Once-daily high-dose edoxaban was associated with significant lower major bleeding episodes compared with once-daily rivaroxaban (risk ratio, 0.76; 95% confidence interval, 0.66–0.89), twice-daily dabigatran 150 mg (risk ratio, 0.78; 95% confidence interval, 0.61–0.84), and twice-daily dabigatran 110 mg (risk ratio, 0.83; 95% confidence interval, 0.71–0.98) and similar bleeding risk compared with twice-daily apixaban (risk ratio, 1.08; 95% confidence interval, 0.91–1.28). Risk of stroke and systemic embolism was similar for the high-dose edoxaban and other nonvitamin K antagonist oral anticoagulant regimens. The low-dose edoxaban regimen was associated with a significant lower risk of major bleeding than other nonvitamin K antagonist oral anticoagulants and a significant higher risk of stroke and systemic embolism compared with apixaban and dabigatran 150 mg. CONCLUSION: Among patients with atrial fibrillation and CHADS(2) score ⩾ 2, the high-dose edoxaban regimen may offer similar efficacy to the other nonvitamin K antagonist oral anticoagulants but with a significant major bleeding benefit over rivaroxaban and dabigatran.