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 Presenter report:
Alexander, John (United States of America )
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Acute coronary syndrome (ACS) patients have recurrent ischemic events despite revascularization and antiplatelet therapy. Novel anticoagulants may reduce these events but also increase bleeding.
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APPRAISE-1 is a phase 2, dose-ranging study of the oral, direct factor Xa inhibitor, apixaban. Patients (n=1715) with recent ST-elevation or non-ST-elevation ACS were randomized to placebo (n=611) or one of 4 doses of apixaban – 2.5mg BID (n=317), 10mg QD (n=318), 10mg BID (n=248), or 20mg QD (n=221) for 6 months. All patients received aspirin. Use of clopidogrel was at the discretion of the treating physician.
The primary outcome was major or clinically relevant non-major bleeding by International Society of Thrombosis and Hemostasis (ISTH) criteria. A secondary outcome was cardiovascular death, myocardial infarction, severe recurrent ischemia or stroke.
The 10mg BID and 20mg QD apixaban arms were discontinued early due to excess bleeding. Results from the placebo and the two lower dose apixaban arms were presented.
Compared to placebo (3.0%), apixaban 2.5mg BID (5.7%, HR 1.78, 95% CI 0.91 to 3.48, p = 0.09) and 10mg QD (7.9%, HR 2.45, 95% CI 1.31 to 4.61, p = 0.005) resulted in a dose dependent increase in ISTH major or clinically relevant non-major bleeding. In addition, apixaban 2.5mg BID (7.6%, HR 0.73, 95% CI 0.44 to 1.19, p=0.21) and 10mg QD (6.0%, HR 0.61, 95% CI 0.35 to 1.04, p=0.07) resulted in trends toward a reduction in clinically important recurrent ischemic events compared to placebo (8.7%).
This is the first experience using a direct factor Xa inhibitor for secondary prevention in ACS patients treated with contemporary antiplatelet therapy. Apixaban, at a daily dose of between 5 and 10mg, appears promising and deserves further clinical investigation.
Discussant : Van de Werf, Frans (Belgium)