ADVANCE-2 apixaban study published in Lancet

The ADVANCE-2 study, which was initially presented last summer at the ISTH meeting in Boston, has now been published in the Lancet. The trial randomized 3057 patients undergoing knee replacement surgery for thormboprophylaxis with either apixaban (2.5 mg daily) or subcutaneous enoxaparin (40 mg once daily).

The primary composite endpoint, consisting of asymptomatic and symptomatic deep vein thrombosis, non-fatal pulmonary embolism, and all-cause death during treatment, was reached in 15% of apixaban patients compared to 24% of enoxaparin patients (p<0.0001).  Bleeding was also reduced in the apixaban group.

ADVANCE-2,  along with its companion trial, ADVANCE-1, shed new light on the highly anticipated new specific factor Xa inhibitor under development by Pfizer and Bristol-Myers Squibb. In contrast to ADVANCE-2, ADVANCE-1, which was published last summer  in the New England Journal of Medicine, missed its primary endpoint and failed to demonstrate that apixaban was noninferior to enoxaparin.

As CardioBrief reported last summer, the primary endpoint in ADVANCE-1, a composite of asymptomatic and symptomatic deep-vein thrombosis, nonfatal pulmonary embolism, and death from any cause during treatment, was reached in 9% of apixaban patients and 8.8% of enoxaparin patients, a result that did not demonstrate noninferiority. According to the investigators, the overall rate of events was lower than anticipated in the trial. On the positive side, the rate of major bleeding and clinically relevant nonmajor bleeding was 2.9% with apixaban and 4.3% with enoxaparin (P=0.03).

It should be noted that in ADVANCE-1 apixaban was compared to the standard US dose of enoxaparin (30 mg twice daily). In ADVANCE-2, by contrast, apixaban was compared to the European standard for enoxaparin (40 mg/day).

In an accompanying comment in the Lancet on the ADVANCE-2 study, Jawed Fareed and Russell Hull write:

The net clinical outcomes are that patients undergoing elective total knee replacement, can benefit from a substantial advancement in the standard of care, and we are potentially a step closer to the unmet need of oral antithrombotic therapy without need for monitoring. For patients undergoing total knee replacement, competing oral antithrombotic regimens are rivaroxaban and dabigatran etexilate.

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  1. […] of intense interest in the last few years. Here are links to previous CardioBrief coverage of the ADVANCE-2 study and the ADVANCE-1 […]

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