Aspirin Linked to Poorer Outcomes in High-Risk Chronic Coronary Syndrome Patients on Long-Term Anticoagulation: New Findings from the AQUATIC Trial

Recent research presented at the ESC Congress 2025 and published in the New England Journal of Medicine highlights concerning outcomes associated with aspirin use among high-risk patients with chronic coronary syndrome (CCS) who are on long-term oral anticoagulation (OAC). The AQUATIC trial revealed that adding aspirin to OAC therapy significantly increased the risk of cardiovascular events, death, and major bleeding.

The study was a double-blind, placebo-controlled, randomized trial involving 872 patients across 51 centers in France. Participants had a history of stent placement over six months prior and were considered high risk due to conditions like diabetes, chronic kidney disease, or diffuse multivessel coronary disease, and were on long-term OAC mainly for atrial fibrillation.

Participants were assigned to receive either aspirin or a placebo, in addition to their OAC, which could be a direct oral anticoagulant or vitamin K antagonist. The primary outcome was a composite of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, and acute limb ischemia. The trial was halted early due to increased mortality in the aspirin group.

Results showed that the group taking aspirin experienced significantly higher rates of adverse events—16.9% experienced the primary efficacy endpoint compared to 12.1% in the placebo group, with an adjusted hazard ratio of 1.53. All-cause mortality was also higher in the aspirin group (13.4% vs. 8.4%), along with a threefold increase in major bleeding events (10.2% vs. 3.4%). Overall, serious adverse events were more common with aspirin.

Professor Martine Gilard, principal investigator, stated that aspirin escalated the risks of major cardiovascular events, death, and bleeding in this population, suggesting that its routine use should be discouraged in high-risk CCS patients on anticoagulants. The findings emphasize the need to reassess current clinical practices and inform future guidelines, especially since the event rates in this study were substantially higher compared to past trials.

This pivotal trial underscores the importance of personalized therapy and the potential dangers of combining aspirin with long-term anticoagulation in vulnerable patients, highlighting a shift in how clinicians approach secondary prevention strategies in complex coronary artery disease cases.

For more details, refer to the publication in the New England Journal of Medicine and the official report from ESC Congress 2025.