Efficacy and safety of direct oral anticoagulants vs vitamin K antagonists for stroke prevention in atrial fibrillation: a systematic review and meta-analysis

Background. Atrial fibrillation (AF) is a common cardiac arrhythmia, with ischemic stroke representing one of its most serious complications. Oral anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) is essential for stroke prevention in patients with AF. Objectives. This systematic review and meta-analysis aimed to compare the efficacy and safety of DOACs versus VKAs in reducing stroke risk and AF-related complications. Methods. We systematically searched PubMed, Europe PMC, Google Scholar, and Scopus for randomized controlled trials and non-randomized studies published up to February 2025 that compared DOACs with VKAs in patients with AF. Outcomes of interest included stroke, all-cause mortality, major bleeding, and intracranial hemorrhage. Random-effects models were used to calculate pooled estimates expressed as hazard ratios or relative risks, with corresponding p-values. Results. Twenty-two studies comprising 91,861 participants were included. DOAC therapy was associated with a significant reduction in stroke risk compared with VKAs (RR = 0.53, p = 0.020). Among individual DOACs, apixaban (p = 0.010) and dabigatran (p = 0.008) significantly reduced stroke and systemic embolic events, whereas rivaroxaban showed a marginal benefit (p = 0.001). All-cause mortality was significantly reduced with dabigatran (p = 0.010) and apixaban (p = 0.050), but not with rivaroxaban (p = 0.160). Apixaban demonstrated the lowest risk of major bleeding (p < 0.001), followed by dabigatran (p = 0.010), while rivaroxaban did not show a significant reduction (p = 0.400). Both dabigatran and apixaban significantly reduced the risk of intracranial hemorrhage (p < 0.001), whereas rivaroxaban did not (p = 0.550). Conclusion. DOACs, particularly apixaban and dabigatran, demonstrated superior efficacy and safety compared with VKAs in reducing stroke, mortality, and bleeding risk in patients with AF. Rivaroxaban showed more limited benefit.