Comparison of Bleeding Risk Between Rivaroxaban and Apixaban for the Treatment of Acute Venous Thromboembolism

VTE is the third leading cause of mortality by cardiovascular disease. Standard treatment for acute VTE uses a combination of parenteral Low-Molecular-Weight Heparin (LMWH) and oral vitamin K antagonists (VKA) for 3 months, and carries significant bleeding risk. The major and/or clinically-relevant non-major bleeding (CRNMB) event rate is reported between 8.1-9.7% during initial treatment. This treatment is burdensome owing to subcutaneous injections, drug interactions, and laboratory monitoring. Direct oral anticoagulants (DOACs) are simpler to use and do not require laboratory monitoring.

Rivaroxaban and apixaban are two DOACs targeting Factor Xa. Each DOAC was separately proven effective and safe when compared to standard treatment. Comparison of the bleeding rates between studies would favour use of apixaban over rivaroxaban; however, trial limitations and lack of direct comparison between these two agents makes it impossible to draw firm conclusions. This represents a dilemma in clinical practice because the absence of convincing differences in safety has led to genuine uncertainty about which DOAC has the best risk-to-benefit ratio.

To address these limitations, a head-to-head randomized controlled trial (RCT) is needed to determine the safety (i.e. bleeding risk) of twice daily apixaban over once daily rivaroxaban during the first 3 months of acute VTE treatment. Eligibility criteria will be less stringent than the COBRRA pilot study and reflect real-world patients. Cost-effective analysis of apixaban twice daily compared to rivaroxaban once daily will also be performed.