Safety and efficacy of rivaroxaban vs. vitamin K antagonists in patients with atrial fibrillation: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

Abstract

Atrial Fibrillation (AF) is a condition that is five times more likely to cause a stroke and necessitates anticoagulation medication. In this regard, rivaroxaban, which is a direct oral anticoagulant (DOAC), has emerged as an alternative to vitamin K agonists (VKAs). Nevertheless, its relative safety and effectiveness compared to VKAs were not well-studied. Thus, a systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to identify the safety and effectiveness of rivaroxaban among patients with AF. The study protocol was registered with PROSPERO (CRD420251059453), and large databases, such as PubMed, Embase, and Scopus, were searched since their inception till March 2025. Outcomes of interest were risk of stroke, myocardial infarction (MI), bleeding, and mortality. The pooled risk ratios (RR) of each outcome were computed using the RevMan random effect model with 95% confidence intervals (CI). In total, four RCTs (n = 17,634) were included, out of which 56.4% of participants were taking rivaroxaban and 43.6% were taking VKAs. Rivaroxaban had a significant effect in reducing the 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 [RR: 0.43 (95% CI 0.29, 0.65), p = 0.0] and intracranial bleeding [RR: 0.63 (95% CI 0.46, 0.86), p = 0.004] while also increasing the risk of death from cardiac causes. There were no significant differences between the cohorts as far as ischemic stroke, MI, Heart Failure hospitalization, mortality, and major and minor bleeding outcomes are concerned. Large-scale trials ought to be carried out to test its importance in enhancing major clinical results such as ischemic stroke, death, and major and minor hemorrhage in AF patients.