Real-world comparative safety and effectiveness of rivaroxaban versus warfarin in patients with non-valvular atrial fibrillation: a prospective cohort study

Background Direct oral anticoagulants (DOACs) provide several advantages over warfarin for stroke prevention in atrial fibrillation, particularly among patients with unstable or difficult-to-control international normalized ratio (INR) values.Objective To compare the safety and efficacy of rivaroxaban versus warfarin in patients with non-valvular atrial fibrillation (NVAF) experiencing challenges in warfarin management.Methods This prospective cohort study included 892 patients with NVAF (rivaroxaban, n = 473; warfarin, n = 419) treated at Kuwait Teaching Hospital, Peshawar, between January 2022 and December 2024, with a 12-month follow-up period. The primary efficacy endpoint was a composite of stroke or systemic embolism, while the primary safety endpoint was major bleeding according to International Society on Thrombosis and Haemostasis (ISTH) criteria. Secondary outcomes included thromboembolic events, bleeding complications, mortality, medication adherence, and treatment discontinuation. Cox proportional hazards regression with multivariable adjustment was applied.Results The primary efficacy endpoint occurred in 4.44% and 7.16% of rivaroxaban and warfarin patients, respectively (HR = 0.63, 95% CI = 0.36–1.10, p = 0.09), indicating a non-significant trend favoring Rivaroxaban. Major bleeding rates were comparable (6.77% vs. 6.92%, p = 0.91), with similar intracranial hemorrhage rates. Rivaroxaban showed significantly higher medication adherence (91.4% vs. 69.3%, p < 0.001), whereas treatment persistence and all-cause mortality were comparable between groups.Conclusions Rivaroxaban demonstrated comparable efficacy and safety to warfarin, with superior medication adherence and no requirement for INR monitoring. These findings suggest that rivaroxaban may represent a practical therapeutic option for patients with NVAF, particularly in healthcare settings with limited monitoring infrastructure.