Efficacy and safety of Edoxaban and Warfarin in patients with atrial fibrillation: a systematic review and meta-analysis

IntroductionAtrial fibrillation is the most prevalent cardiac arrhythmia in the United States and substantially increases the risk of stroke and heart failure in patients with non-valvular atrial fibrillation, those undergoing percutaneous coronary intervention, and transcatheter aortic valve repair. Warfarin, a vitamin K antagonist, has long been the standard anticoagulant therapy but is limited by drug interactions and monitoring requirements, while edoxaban, a factor Xa inhibitor, has shown favorable bleeding outcomes. MethodsThis meta-analysis included five randomized controlled trials identified through a comprehensive search of PubMed, Medline, Embase, Google Scholar, CENTRAL, and ClinicalTrials.gov from January 2014 to October 2024 (PROSPERO ID: CRD420250648890). Data were pooled using the inverse variance method with hazard ratios and 95% confidence intervals, DerSimonian-Laird random-effects model was applied in Stata version 17. Risk of bias was assessed using the Cochrane RoB v2 tool and certainty of evidence using GRADE assessment tool, with statistical significance set at P < 0.05. ResultsEdoxaban demonstrated a greater reduction in stroke or systemic embolism overall but was less effective in patients with prior myocardial infarction (HR 0.58, 95% CI 0.32-1.05). Major adverse cardiovascular events marginally favored edoxaban over warfarin (HR 0.90, 95% CI 0.83-0.98, P = 0.01), whereas warfarin performed better in patients with CHA2DS2-VASc scores [&ge;]4. No significant difference was observed in all-cause mortality (P = 0.32). For clinically relevant non-major bleeding, warfarin was more favorable in patients aged [&ge;]65 years and those with normal renal function, while edoxaban reduced major bleeding more effectively in patients with <25% heart failure; warfarin showed slight superiority when heart failure prevalence was [&ge;]25%. ConclusionOverall, edoxaban shows robust efficacy across multiple outcomes, while warfarin remains essential in specific high-risk subgroups, warranting further confirmatory studies.