Apixaban vs rivaroxaban for venous thromboembolism: a systematic review and meta-analysis

Direct oral anticoagulants are first-line therapy for venous thromboembolism (VTE), yet comparative evidence between apixaban and rivaroxaban remains limited. This systematic review and meta-analysis aimed to compare the efficacy and safety of apixaban versus rivaroxaban in patients with VTE. A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library was conducted from inception through March 2026. Studies directly comparing apixaban and rivaroxaban in adult VTE patients were included. Outcomes, including recurrent VTE, major bleeding, all-cause mortality, and net clinical harm, were pooled using a random-effects model. Thirteen studies comprising more than 220,000 patients were included. Apixaban was associated with a significantly lower risk of recurrent VTE compared to rivaroxaban (RR 0.85; 95% CI 0.74-0.98), with moderate heterogeneity. Apixaban was also associated with a significant 28% reduction in major bleeding risk (RR 0.72; 95% CI 0.65-0.81), with low heterogeneity, indicating consistent findings across studies. When efficacy and safety outcomes were combined, apixaban demonstrated a significantly lower risk of net clinical harm (RR 0.76; 95% CI 0.68-0.86). In contrast, no statistically significant difference was observed in all-cause mortality (RR 0.95; 95% CI 0.80-1.12), with substantial heterogeneity across studies. Sensitivity analyses confirmed the robustness of these findings, with no single study significantly altering the overall estimates. Overall, apixaban demonstrated a more favorable efficacy and safety profile compared with rivaroxaban in VTE management, with reduced recurrence and bleeding risk, while mortality remained comparable. These findings suggest that apixaban may be associated with a more favorable efficacy and safety profile than rivaroxaban; however, the results should be interpreted cautiously given the predominance of observational evidence.