Atrial Fibrillation (AF) substantially increases the risk of stroke and frequently requires long-term anticoagulation therapy. Direct oral anticoagulants, including Rivaroxaban, have emerged as alternatives to traditional vitamin K antagonists (VKAs), although comparative safety and efficacy data remain under evaluation. A systematic review and meta-analysis of randomized controlled trials published in the European Journal of Medical Research assessed the clinical outcomes associated with rivaroxaban compared with VKAs in patients with AF.

The review protocol was registered with PROSPERO (CRD420251059453). Comprehensive searches of PubMed, Embase, and Scopus were conducted from database inception through March 2025. Eligible studies were randomized controlled trials enrolling patients with AF that compared rivaroxaban with VKAs and reported outcomes including stroke, myocardial infarction (MI), bleeding events, or mortality. Pooled risk ratios (RRs) were calculated using a random-effects model with 95% confidence intervals (CI).
Four randomized controlled trials including 17,634 participants met the inclusion criteria.

Among these, 56.4% received rivaroxaban and 43.6% received VKAs. Rivaroxaban was associated with reduced risk of hemorrhagic stroke (RR 0.59; 95% CI 0.37–0.94; p=0.03), systemic embolism (RR 0.36; 95% CI 0.18–0.71; p=0.003), fatal bleeding (RR 0.43; 95% CI 0.29–0.65), and intracranial bleeding (RR 0.63; 95% CI 0.46–0.86; p=0.004). No statistically significant differences were observed for ischemic stroke, MI, heart failure hospitalization, overall mortality, or major and minor bleeding outcomes. An increased risk of death from cardiac causes was reported with rivaroxaban.

The analysis suggests differences in specific bleeding and embolic outcomes between rivaroxaban and VKAs. Further large-scale trials are warranted to evaluate effects on major clinical outcomes including ischemic stroke, mortality, and bleeding.