Key result
Adding apixaban to antiplatelet therapy after ACS increases clinically significant bleeding by ~145%.
Why the study?
Patients remain at risk of recurrent events after acute coronary syndrome, and the safety and efficacy of adding apixaban to antiplatelet therapy were uncertain.
Does apixaban added to antiplatelet therapy increase bleeding or reduce ischemic events in patients with recent acute coronary syndrome?
RCT (n=1,715)
double-blind
randomized
Does apixaban added to antiplatelet therapy increase bleeding or reduce ischemic events in patients with recent acute coronary syndrome?
Adding apixaban to antiplatelet therapy after acute coronary syndrome causes a dose-dependent increase in bleeding with a trend toward reduced ischemic events, with safety and efficacy varying by background antiplatelet therapy.
Answers are grounded in this paper and cite their sources.
Apixaban addition to antiplatelet therapy post-ACS raises bleeding concerns precluding higher doses; extends safety data against routine NOAC use in this setting.
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. METHODS AND RESULTS: Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) was a phase 2, double-blind, placebo-controlled, dose-ranging study. Patients (n=1715) with recent ST-elevation or non-ST-elevation acute coronary syndrome were randomized to 6 months of placebo (n=611) or 1 of 4 doses of apixaban: 2.5 mg twice daily (n=317), 10 mg once daily (n=318), 10 mg twice daily (n=248), or 20 mg once daily (n=221). Nearly all patients received aspirin; 76% received clopidogrel. The primary outcome was International Society of Thrombosis and Hemostasis major or clinically relevant nonmajor bleeding. A secondary outcome was cardiovascular death, myocardial infarction, severe recurrent ischemia, or ischemic stroke. At the recommendation of the Data Monitoring Committee, 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. 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. The increase in bleeding was more pronounced and the reduction in ischemic events was less evident in patients taking aspirin plus clopidogrel than in those taking aspirin alone. CONCLUSIONS: We observed a dose-related increase in bleeding and a trend toward a reduction in ischemic events with the addition of apixaban to antiplatelet therapy in patients with recent acute coronary syndrome. The safety and efficacy of apixaban may vary depending on background antiplatelet therapy. Further testing of apixaban in patients at risk of recurrent ischemic events is warranted.
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Investigators et al. (2009) conducted an RCT in acute coronary syndrome (n=1,715). Apixaban vs. placebo was evaluated on International Society of Thrombosis and Hemostasis major or clinically relevant nonmajor bleeding (HR 2.45, 95% CI 1.31-4.61, p=0.005). Apixaban added to antiplatelet therapy after acute coronary syndrome caused a dose-dependent increase in major or clinically relevant nonmajor bleeding (HR 2.45, 95% CI 1.31-4.61 for 10 mg once daily).
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