The COBRRA trial, published in NEJM in March, is the first randomised comparison of the two most prescribed direct oral anticoagulants (DOACs) for acute VTE. Castellucci and his team enrolled 2,760 patients with symptomatic pulmonary embolism (PE) or proximal deep vein thrombosis (DVT). This study took place at 32 sites in Canada, Australia, and Ireland.
Patients were randomised in a 1:1 ratio to standard dosing regimens:
Apixaban 10 mg twice daily for 7 days, then 5 mg twice daily,
or rivaroxaban 15 mg twice daily for 21 days, then 20 mg daily.
The primary outcome was clinically relevant bleeding over three months, and the results were striking. Bleeding occured in 3.3% of the apixaban group, compared to 7.1% in the rivaroxaban group. This shows a 54% relative risk reduction (RR 0.46; 95% confidence interval [CI] 0.33 to 0.65; P<0.001). Major bleeding was 0.4% versus 2.4%. There was no significant difference in recurrent VTE between the two groups.
The primary outcome was clinically relevant bleeding over three months, and the results were striking. Bleeding occured in 3.3% of the apixaban group, compared to 7.1% in the rivaroxaban group. This shows a 54% relative risk reduction (RR 0.46; 95% confidence interval [CI] 0.33 to 0.65; P<0.001). Major bleeding was 0.4% versus 2.4%. There was no significant difference in recurrent VTE between the two groups.
The likely explanation is dosing. Rivaroxaban’s loading phase is 15 mg twice daily for 21 days, compared with apixaban’s 10 mg twice daily for just 7 days. That longer, higher-dose window appears to drive most of the bleeding divergence.
Important caveats. This was an open-label trial with blinded endpoint adjudication. It followed patients for only three months, and the population was mostly white. It is a single study, and we should be cautious about treating it as the final word. This is the first randomised evidence directly comparing these two drugs for VTE. The signal is clear and clinically important.
The COBRRA-AF trial, comparing the same two drugs in atrial fibrillation (AF), where there is no loading dose, is underway. This will help show if the safety gap continues in another clinical setting or if the dosing strategy is the main factor.
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