Mount Sinai Med-Lit Review
Clinical Question: In patients with chronic coronary syndrome and high atherothrombotic risk on long-term oral anticoagulation, does the addition of aspirin improve outcomes?
Background: The ideal antithrombotic regimen for patients with chronic coronary syndrome at high atherothrombotic risk on oral anticoagulation has been a clinical challenge, particularly for those with a history of prior stenting. While some prior trials suggest that oral anticoagulation monotherapy may be sufficient beyond six months post percutaneous coronary intervention (PCI), robust evidence in contemporary high-risk populations has been limited. The AQUATIC trial sought to answer this question.
Study design: Multicenter, double-blind, randomized, placebo-controlled trial
Setting: A total of 51 centers in France
Synopsis: Eligible patients had chronic coronary syndrome with prior stenting more than six months before enrollment and were on a long-term oral anticoagulant. The trial was stopped early, after a median follow-up of 2.2 years, due to excess mortality in the aspirin group. A total of 872 patients underwent randomization; 433 were assigned to the aspirin group (100 mg daily), and 439 to the placebo group. All subjects received ongoing oral anticoagulation (90% direct oral anticoagulants).
At baseline, mean age and CHA2DS2-VASc score were 72 years and 4, respectively; 85% were male, and nearly three-quarters had a history of myocardial infarction. The primary efficacy endpoint (a composite of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia) occurred in 16.9% of patients receiving aspirin versus 12.1% with placebo (adjusted hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.07 to 2.18; P=0.02). All-cause death was significantly higher with aspirin (13.4% versus 8.4%; adjusted HR, 1.72; 95% CI, 1.14 to 2.58; P=0.01), largely driven by cardiovascular mortality; major bleeding was tripled in the aspirin group (10.2% versus 3.4%; adjusted HR, 3.35; 95% CI, 1.87 to 6.00; P <0.001).
The absolute risk increase for thrombotic events in the dual-pathway arm was nearly 5%, a number needed to harm of only 21, which was very surprising when compared to prior trials. In addition, the bleeding risk was more than 5%, and the number needed to harm was only 15. However, the trial has limitations, including premature termination with consequent loss of statistical power.
Bottom line: The AQUATIC trial shows that among patients with chronic coronary syndrome and high atherothrombotic risk on oral anticoagulant monotherapy, the addition of aspirin increased the risk of a composite of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia, as well as all-cause mortality and major bleeding, suggesting that “less is more” in these patients.
Citation: Lemesle G. Aspirin in patients with chronic coronary syndrome receiving oral anticoagulation. N Engl J Med. 2025;393(16):1578-1588. doi: 10.1056/NEJMoa2507532.
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Dr. Dey
Dr. Dey is an assistant professor of medicine at the Icahn School of Medicine at Mount Sinai in New York.