Abstract Body (Do not enter title and authors here): Background: Optimal anticoagulation in non-valvular atrial fibrillation (AF) remains critical to minimizing stroke and systemic thromboembolism. While direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists (VKAs), comparative real-world outcome data remain inconsistent, particularly regarding bleeding risk.
Objective: To evaluate the comparative efficacy and safety of DOACs versus VKAs in patients with non-valvular AF, with focus on cerebrovascular events, all-cause mortality, and major bleeding.
Methods: This systematic review and meta-analysis adhered to PRISMA 2020 guidelines. Randomized controlled trials and observational studies comparing DOACs with VKAs in adults with non-valvular AF were identified. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effects modelling. Outcomes included cerebrovascular events (stroke/systemic embolism), all-cause mortality, and major bleeding. Risk stratification was assessed using CHA₂DS₂-VASc and HAS-BLED. Heterogeneity was measured using the I² statistic.
Results: Across 11 studies involving over 125,075 patients, DOACs significantly reduced the risk of cerebrovascular events compared to VKAs (HR 0.88; 95% CI 0.80–0.96; p < 0.01; I² = 0%) and all-cause mortality (HR 0.87; 95% CI 0.83–0.92; p < 0.00001; I² = 0%). Major bleeding risk was not significantly different between groups (HR 0.86; 95% CI 0.73–1.01; p = 0.07), with substantial heterogeneity (I² = 82%) attributed to differences in age, renal function, and antiplatelet co-therapy.
Conclusion: DOACs offer superior stroke prevention and mortality reduction in non-valvular AF without a significant increase in major bleeding risk. These findings support DOACs as first-line agents in evidence-based AF management while emphasizing the need for individualized risk stratification and renal dose adjustment.