Apixaban After Acute Coronary Syndromes Increases Bleeding Risk

Faced with an abundance of novel anticoagulants, clinicians are at pains to learn the names and indications of many new drugs at once. Apixaban, an oral, direct factor Xa inhibitor, has shown promise for thromboprophylaxis after surgery and possibly for stroke prevention in patients with atrial fibrillation (AF; JW Hosp Med Dec 22 2010 and JW Cardiol Feb 10 2011). To explore whether the drug reduces recurrent ischemia after acute coronary syndromes (ACSs), investigators for the manufacturer-sponsored APPRAISE-2 trial randomized 7392 patients to receive apixaban or placebo in addition to standard antiplatelet therapy after ACS. All patients had at least two risk factors for recurrent ischemia (e.g., age ≥65, diabetes, prior myocardial infarction [MI]). The primary efficacy outcome was the composite of cardiovascular death, MI, and ischemic stroke; major bleeding was assessed by the Thrombolysis in MI criteria.

The trial was terminated early at a median follow-up of approximately 8 months because of an excess of bleeding events without a concomitant benefit in the apixaban group compared with the placebo group. The primary endpoint occurred in 7.5% of the apixaban group and 7.8% of the placebo group (hazard ratio, 0.95; P=0.51). In on-treatment analysis, major bleeding occurred in 1.3% of apixaban recipients and 0.5% of placebo recipients (HR, 2.59; P=0.001)