Safety and Efficacy of Direct Oral Anticoagulants Versus Vitamin K Antagonists for Cerebrovascular Ischemic Outcomes in Non‐Valvular Atrial Fibrillation: A Systematic Review and Meta‐Analysis

BACKGROUND: Atrial fibrillation (AF) is a major cause of thromboembolic events, including ischemic stroke and transient ischemic attack (TIA). While Vitamin K antagonists (VKAs) have long been used for stroke prevention, Direct Oral Anticoagulants (DOACs) have emerged as potential alternatives due to improved pharmacologic profiles and safety. This systematic review and meta-analysis aimed to compare the efficacy and safety of DOACs versus VKAs in patients with non-valvular AF, with a focus on cerebrovascular ischemic outcomes. METHODS: A comprehensive search of PubMed, ClinicalTrials.gov, and Cochrane Library was performed in accordance with PRISMA 2020 guidelines. Randomized controlled trials and comparative observational studies reporting cerebrovascular events, major bleeding, and all-cause mortality were included. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random-effects model. RESULTS: Eleven studies encompassing 814 716 patients were included. DOAC use was associated with a significantly lower risk of recurrent cerebrovascular ischemic events compared with VKAs (RR 0.83, 95% CI 0.78-0.88, p < 0.0001). The risk of major bleeding was also reduced with DOACs (RR 0.77, 95% CI 0.71-0.82, p < 0.0001). All-cause mortality was similar between groups (RR 1.02, 95% CI 0.34-3.13), though sensitivity analysis excluding one heterogeneous study favored DOACs (RR 0.79, 95% CI 0.63-0.98). CONCLUSION: In patients with non-valvular AF, DOACs demonstrate superior efficacy in reducing cerebrovascular ischemic outcomes and lower bleeding risk compared to VKAs, with comparable mortality outcomes. These findings support current guidelines recommending DOACs as first-line anticoagulation for stroke prevention in AF.