Apixaban Shows Superior Bleeding Profile Compared to Rivaroxaban in VTE Treatment

Patients treated with apixaban (Eliquis. Bristol Myers Squibb) for three months after acute venous thromboembolism (VTE) experienced a significantly lower rate of clinically relevant bleeding compared to those treated with rivaroxaban (Xarelto; Bayer/Janssen), according to results from the COBRRA trial .

The findings, published in the Latest England Journal of Medicine on March 12/19, 2026, suggest a clear benefit to using apixaban over rivaroxaban following years of uncertainty regarding the optimal direct oral anticoagulant (DOAC) for this condition .

COBRRA Trial Details

The COBRRA trial, an international, pragmatic, prospective, randomized, open-label, blinded end-point study, involved 2,760 patients with acute symptomatic pulmonary embolism (PE) or proximal deep vein thrombosis (DVT) . Participants were randomized to receive either apixaban or rivaroxaban for a three-month period.

• Apixaban Dosage: 10 mg twice daily for 7 days, followed by 5 mg twice daily.
• Rivaroxaban Dosage: 15 mg twice daily for 21 days, followed by 20 mg daily.

The primary outcome measured was clinically relevant bleeding, defined as major bleeding or clinically relevant nonmajor bleeding according to the International Society on Thrombosis and Haemostasis (ISTH) criteria .

Key Findings

The study revealed a substantial difference in bleeding risk between the two medications:

• Clinically Relevant Bleeding: 3.3% in the apixaban group versus 7.1% in the rivaroxaban group (relative risk, 0.46; 95% confidence interval [CI], 0.33 to 0.65; P<0.001) .
• Major Bleeding: 0.4% in the apixaban group versus 2.4% in the rivaroxaban group (relative risk, 0.16; 95% CI, 0.06-0.40) .
• Clinically Relevant Nonmajor Bleeding: 2.9% in the apixaban group versus 4.9% in the rivaroxaban group (relative risk, 0.59; 95% CI, 0.40-0.86) .

Importantly, there were no significant differences observed in rates of recurrent symptomatic VTE (1.1% vs 1.0%; RR 1.08; 95% CI 0.52-2.23) or all-cause death (0.1% vs 0.3%; RR 0.25; 95% CI, 0.03-2.26) between the two groups .

Expert Commentary

“As much as we were expecting to see a bleeding difference, I don’t feel any of us expected to see that much of a bleeding difference,” said Lana A. Castellucci, MD, lead author of the study .

Lisa K. Moores, MD, in an accompanying editorial, suggested that these findings should prompt a review of current guidelines, stating that “apixaban is a safer first-line option than rivaroxaban for minimizing the risk of bleeding without compromising the prevention of recurrent thrombosis” .

Gregory Piazza, MD, noted that whereas the data strongly support apixaban as a first-line option, individual patient factors may still warrant the use of rivaroxaban in certain cases .

Implications and Future Research

The COBRRA trial provides compelling evidence for the superior safety profile of apixaban compared to rivaroxaban in the treatment of acute VTE. Researchers are continuing to investigate the optimal use of these DOACs in other patient populations, such as those with malignancy and thrombosis and in conditions like atrial fibrillation through the ongoing COBRRA-AF trial .