Patients with chronic coronary syndrome and at high atherothrombotic risk who received aspirin in addition to their current oral anticoagulation therapy had a higher risk of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia than those taking a placebo, according to results from the AQUATIC study presented at ESC Congress 2025 and simultaneously published in NEJM.

Researchers randomized 872 patients in France to receive (100 mg once daily) or placebo. All patients had chronic coronary syndrome and had undergone a previous stent implantation (>6 months before enrollment) and were at high atherothrombotic risk. They were also on long-term anticoagulation therapy. The trial was stopped early after a median follow-up of two years due to an excess of deaths from any cause in the aspirin group.

In presenting the results, researchers said a primary efficacy outcome event occurred in 73 patients (16.9%) in the aspirin group compared with 53 patients (12.1%) in the placebo group. Death from any cause was also higher among those in the aspirin group (13.4%) vs. the placebo group (8.4%), as were the number of serious adverse events (467 vs. 395, respectively). Study investigators also noted a more than three-fold higher risk of major bleeding among those receiving aspirin vs. placebo (10.2% vs. 3.4%, respectively).

"Other studies have investigated antithrombotic therapy for stable coronary artery disease and atrial fibrillation, but this is the first randomized trial to include patients who had prior stenting and with high atherothrombotic risk," said Martine Gilard, MD, who presented the findings. "Event rates were around seven times higher in AQUATIC than in previous trials. Our findings can now be considered in future ESC Guidelines to build on current recommendations, which are based on expert consensus."