Aspirin Added to Oral Anticoagulation Increases Mortality and Bleeding

 Results from the international AQUATIC trial, published in The New England Journal of Medicine and presented at ESC 2025, challenge the long-standing practice of combining aspirin with long-term oral anticoagulation in patients with chronic coronary syndrome.

The study enrolled patients who had undergone stenting more than six months earlier and were already receiving oral anticoagulants. Participants were randomized to receive either aspirin 100 mg/day or placebo, in addition to their anticoagulant therapy. The trial was terminated early due to excess mortality in the aspirin arm.

Key findings:

• All-cause mortality: 13.4% with aspirin vs. 8.4% with placebo (OR 1.72; 95% CI, 1.14–2.58).
• Composite endpoint (CV death, myocardial infarction, stroke, systemic embolism, revascularization, acute limb ischemia): 16.9% vs. 12.1% (OR 1.53; 95% CI, 1.07–2.18).
• Major bleeding: 10.2% vs. 3.4% (OR 3.35; 95% CI, 1.87–6.00).

Conclusion: In patients with chronic coronary syndrome on long-term oral anticoagulation, adding aspirin did not reduce thrombotic events but significantly increased both bleeding and overall mortality. The authors emphasize that clinical practice guidelines may need to be reconsidered for this patient population.

https://www.nejm.org/doi/full/10.1056/NEJMoa2507532