For Post-stent Patients With Atherosclerotic Coronary Vascular Disease Who Are Taking an Anticoagulant, Adding Aspirin Worsens Outcomes

For patients with atherosclerotic coronary vascular disease and a stent who have high residual atherosclerotic risk and an indication for anticoagulation, is aspirin plus anticoagulation preferred over anticoagulation alone?

The superior trial should end adding supplemental aspirin for patients with atherosclerotic coronary vascular disease and atrial fibrillation who are taking an anticoagulant. Even in this very high-risk population, adding aspirin increased mortality (number needed to harm [NNH] = 21) compared with anticoagulation alone. (Level of Evidence = 1b)

The French investigators identified 872 patients with atherosclerotic coronary vascular disease, previous stent implantation (percutaneous coronary intervention) at least 6 months ago, and who had an indication for anticoagulation (atrial fibrillation for 90%). They also had to have a high residual atherothrombotic risk based on conditions such as diabetes, diffuse multivessel disease, chronic kidney disease, previous stent thrombosis, or multiple or complicated stents. Patients received an anticoagulant chosen by their physician (62% were given apixaban [Eliquis], 25% rivaroxaban [Xarelto]) and were randomized to receive aspirin, 100 mg once daily, or matching placebo. The randomization was stratified by type of anticoagulant, study site, and whether they were taking an antiplatelet agent at baseline. Analysis was by intention to treat and allocation was concealed. Groups were balanced at baseline with a mean age of 72 years and a median time of 3 years since their percutaneous coronary intervention; 85% were men, and 72% had a history of myocardial infarction. Enrollment was stopped early after 4 years (before reaching the target enrollment of 2,000 patients) due to a significant excess of deaths in the aspirin group. The median follow-up at that time was 2.2 years. The composite of six adverse cardiovascular events occurred more often in the aspirin group (16.9% vs 12.1%; P = .02; NNH = 21). All-cause mortality (13.4% vs 8.4%; P = .01; NNH = 20) and major bleeding (10.2% vs 3.4%; P < .001; NNH = 15) also occurred more often in the aspirin group. No primary or secondary outcomes favored aspirin over placebo.

Study Design: Randomized controlled trial (double-blinded)

Funding Source: Government

Allocation: Concealed

Setting: Outpatient (specialty)

Reference: Lemesle G, Didier R, Steg PG, et al.; AQUATIC Trial Investigators. Aspirin in patients with chronic coronary syndrome receiving oral anticoagulation. N Engl J Med. 2025;393(16):1578-1588.

Editor’s Note: Dr. Ebell is cofounder and editor-in-chief of Essential Evidence Plus.