Bleeding Risk with Apixaban vs. Rivaroxaban: NEJM March 2026

Clinical Summary

In this randomized international trial (COBRRA), investigators compared the bleeding risk of apixaban vs. rivaroxaban in patients with acute venous thromboembolism (VTE), including pulmonary embolism and proximal deep-vein thrombosis. A total of 2,760 patients were randomized to receive either apixaban (10 mg twice daily for 7 days followed by 5 mg twice daily) or rivaroxaban (15 mg twice daily for 21 days followed by 20 mg daily) for 3 months.

The primary endpoint—clinically relevant bleeding (major or clinically relevant nonmajor bleeding)—occurred significantly less often with apixaban (3.3%) compared with rivaroxaban (7.1%), corresponding to a 54% relative risk reduction (RR 0.46; 95% CI 0.33–0.65; P<0.001). Mortality rates were low and similar between groups.

Clinical implication: Apixaban demonstrated a substantially lower bleeding risk than rivaroxaban while maintaining similar clinical outcomes, suggesting it may be the safer first-line direct oral anticoagulant for treatment of acute VTE in routine clinical practice.