The risk of clinically relevant bleeding was significantly lower with apixaban compared with rivaroxaban among patients with acute venous thromboembolism (VTE) during a three-month treatment period, according to results of the COBRRA trial published March 11 in NEJM.
In the open-label, blinded-endpoint international trial, investigators randomized 2,760 patients (mean age, 58 years; 44% women) with acute symptomatic pulmonary embolism or proximal deep-vein thrombosis 1:1 to three months of apixaban (10 mg twice daily for seven days, followed by 5 mg twice daily) or rivaroxaban (15 mg twice daily for 21 days followed by 20 mg daily).
Results at three months showed that 44 of 1,345 (3.3%) patients in the apixaban arm and 96 of 1,355 (7.1%) in the rivaroxaban arm experienced a primary outcome of clinically relevant bleeding, defined as a composite of major bleeding or clinically relevant nonmajor bleeding (relative risk, 0.46; p<0.001). One patient in the apixaban arm and four patients in the rivaroxaban arm died from any cause, with no deaths attributed to bleeding or recurrent VTE.
Serious adverse events not related to bleeding or VTE occurred in 2.7% and 2.2% of patients in the apixaban and rivaroxaban arms.
Trial authors L.A. Castellucci, MD, et al., note that the difference in risk may be due to the larger initial dose of rivaroxaban, given that the main difference in outcomes occurred within the first three weeks on the higher dose, and write that “further evaluation in clinical trials is needed to confirm whether the rivaroxaban dosing regimen contributed to the observed bleeding risks.”
In an accompanying editorial comment, Lisa K. Moores, MD, calls the results “striking,” noting the more than 50% decrease in risk of bleeding without a change in efficiency with apixaban.
“By confirming the safety advantage of apixaban over rivaroxaban in a randomized trial, these results should prompt a reevaluation of current guidelines,” she concludes. “For many patients with acute [VTE], the choice of anticoagulant is no longer a toss-up.”