Key result
Apixaban added to aspirin or aspirin plus clopidogrel after ACS did not reduce cardiovascular death, MI, or ischemic stroke but increased major bleeding.
Why the study?
Bleeding limits anticoagulant treatment in ACS patients, prompting investigation into whether background concomitant antiplatelet therapy influences the effects of apixaban after ACS.
Does apixaban reduce cardiovascular events or increase bleeding when added to mono or dual antiplatelet therapy in high-risk ACS patients?
RCT (n=7,364)
randomized
Does apixaban reduce cardiovascular events or increase bleeding when added to mono or dual antiplatelet therapy in high-risk ACS patients?
Hazard Ratio: 0.95 (95% CI 0.78–1.14)
Absolute Event Rate: 13.22% vs 14.24%
p-value: p(interaction)= 0.84
Adding apixaban to mono or dual antiplatelet therapy after an acute coronary syndrome does not improve ischemic outcomes but significantly increases the risk of major bleeding.
Apixaban effects may vary by antiplatelet regimen in ACS; leaves open confirmation in prospective trials.
BACKGROUND: Bleeding limits anticoagulant treatment in patients with acute coronary syndromes (ACS). OBJECTIVES: We investigated whether background concomitant antiplatelet therapy influences the effects of apixaban after ACS. METHODS: This study examined high-risk ACS patients who were treated with aspirin or aspirin plus clopidogrel and who were randomized to apixaban 5 mg twice daily or placebo. In a post-hoc analysis, we assessed whether the effect of apixaban on efficacy and safety outcomes varied by the concomitant antiplatelet regimen by using simple Cox modeling and marginal structural models with propensity scores and antiplatelet therapy as a time-dependent covariate. RESULTS: At baseline, of 7,364 patients, 16.3% (n = 1,202) were on aspirin alone, and 79.0% (n = 5,814) were on aspirin plus clopidogrel. A total of 19.2% (n = 1,415) switched antiplatelet therapy during follow-up. No differential effect of apixaban versus placebo was observed for the composite endpoint of cardiovascular death, myocardial infarction, and ischemic stroke in patients taking aspirin (12.21 per 100 patient-years vs. 13.21 per 100 patient-years; adjusted hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.62 to 1.32) or aspirin plus clopidogrel (13.22 vs. 14.24; adjusted HR: 0.95; 95% CI: 0.78 to 1.14; p(interaction)= 0.84). Compared with placebo, apixaban increased Thrombolysis In Myocardial Infarction major bleeding in patients taking aspirin (1.48 vs. 0.25; adjusted HR: 6.62; 95% CI: 0.75 to 51.73) and in patients taking aspirin plus clopidogrel (2.58 vs. 1.02; adjusted HR: 2.44; 95% CI: 1.34 to 4.45; p(interaction)= 0.41). Similar results were obtained with marginal structural models and in patients treated with and without percutaneous coronary intervention. CONCLUSIONS: Post-ACS treatment with apixaban versus placebo showed no efficacy, but it increased bleeding regardless of concomitant therapy with aspirin alone or aspirin plus clopidogrel. (Apixaban for Prevention of Acute Ischemic Events 2 [APPRAISE-2]; NCT00831441).
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Hess et al. (2015) conducted an RCT in acute coronary syndromes (n=7,364). Apixaban vs. Placebo was evaluated on Composite of cardiovascular death, myocardial infarction, and ischemic stroke (aspirin plus clopidogrel stratum) (adjusted HR 0.95, 95% CI 0.78 to 1.14, p=p(interaction)= 0.84). Apixaban added to aspirin or aspirin plus clopidogrel after ACS did not reduce cardiovascular death, MI, or ischemic stroke but increased major bleeding.
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