Authors
Alexander JH, Becker RC, Bhatt DL, et al. APPRAISE Steering Committee and investigators.
Title
Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome: results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) trial.
References
Circulation 2009;119:2877-85.
Background
After an acute coronary syndrome, patients remain at risk of recurrent events. Apixaban, an oral direct factor Xa inhibitor, is a novel anticoagulant that may reduce these events but also poses a risk of bleeding.
Purpose
To investigate the role of Apixaban in patients with STEMI and non-STEMI ACS on bleeding events and cardiovascular events
Design
Phase 2, international multi-centre, double-blind, placebo-controlled, dose-ranging study Patients (n=1715) with recent ST-elevation or non-ST-elevation acute coronary syndrome Primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcome was cardiovascular death, myocardial infarction, severe recurrent ischemia, or ischemic stroke.
Exclusion Criteria
Aspirin allergy Planned catheterization, percutaneous coronary intervention, coronary bypass surgery, or other invasive procedure Persistent severe hypertension Severe renal insufficiency Active bleeding or a high risk for bleeding Coagulopathy Stroke within 3 months NYHA IV heart failure Thrombocytopenia Anemia An indication for ongoing anticoagulation Long-term NSAID or high-dose ASA Treatment with strong CYP3A4 inhibitors
Follow-Up
6 months
Treatment Regimen
Randomized to 6 months placebo or 1 of 4 regimens of apixaban All patients received ASA; 76% received clopidogrel
Results
Primary Endpoints: The 2 higher-dose apixaban arms were discontinued because of excess total bleeding. Compared with placebo, apixaban 2.5 mg twice daily (hazard ratio, 1.78; 95% confidence interval, 0.91 to 3.48; P=0.09) and 10 mg once daily (hazard ratio, 2.45; 95% confidence interval, 1.31 to 4.61; P=0.005) resulted in a dose-dependent increase in major or clinically relevant nonmajor bleeding. Secondary Endpoints: Apixaban 2.5 mg twice daily (hazard ratio, 0.73; 95% confidence interval, 0.44 to 1.19; P=0.21) and 10 mg once daily (hazard ratio, 0.61; 95% confidence interval, 0.35 to 1.04; P=0.07) resulted in lower rates of ischemic events compared with placebo.
Summary
Especially in patients taking ASA and clopidgrel, the increase in bleeding was more pronounced than the reduction in ischemic events. The safety and efficacy of apixaban may vary depending on concomitant anti-platelet therapy. Further studies are warranted in patients at risk for ischemic events.
Implications
The addition of Apixaban to DAPT is not recommended, since this leads to an increase in bleeding, with no clear benefit in reduction of ischemic events.
Related Figures
None.