Efficacy and safety of rivaroxaban versus apixaban for venous thromboembolism: A systematic review and meta-analysis of observational studies

Background: Direct-acting oral anticoagulants (DOACs) including rivaroxaban and apixaban are preferred over vitamin K antagonists for the treatment of venous thromboembolism (VTE). We conducted a systematic review and a meta-analysis to compare the efficacy and safety of rivaroxaban versus apixaban in the treatment of VTE. Methods: We conducted an electronic search for studies that directly compared treatment with rivaroxaban and apixaban in adult patients with VTE. The relative risks (RRs) and 95% confidence intervals (CIs) were estimated and pooled using a fixed-effect model unless significant heterogeneity was present (I² > 40%), then random-effects model was used. The primary efficacy and safety outcomes were recurrent VTE (rVTE) and major bleeding events, respectively. Results: Nine observational studies were included in our meta-analysis, assessing 24,156 patients for apixaban and 38,847 for rivaroxaban. Pooling of data for our primary efficacy outcome showed a trend towards lower risk of rVTE with apixaban compared to rivaroxaban (RR 0.77, 95% CI 0.57–1.04, I² = 53%). Analysis of our primary safety outcome showed a significantly lower risk of major bleeding with apixaban compared to rivaroxaban (RR 0.68, 95% CI 0.61–0.76, I² = 0%). Apixaban was associated with significantly decreased risk of net clinical harm, clinically relevant non major bleeding (CRNMB) and any bleeding, compared to rivaroxaban (RR 0.75, 95% CI 0.61–0.92, I² = 50%; RR 0.58, 95% CI 0.50–0.67, I² = 7%; RR 0.64, 95% CI 0.59–0.70, I² = 0%, respectively). Conclusions: Apixaban is associated with a significantly lower risk of major bleeding compared to rivaroxaban for treatment of VTE. Given the limitations of the existing evidence, further interventional studies comparing the two drugs are needed.