Termination of French Aspirin Trial for Chronic Coronary Syndrome

A recent clinical trial in France aimed at evaluating the necessity of long-term aspirin treatment for patients with chronic coronary syndrome has been halted. The decision was made due to concerns that the potential harms to participants outweighed any benefits of continuing the trial.

Concerns Regarding Aspirin Use

Heart specialists had previously voiced apprehensions about the addition of aspirin to existing medication regimens, suggesting that it might be more harmful than beneficial. This prompted French clinicians to rigorously assess the safety profile of aspirin.

Findings on Long-term Aspirin Prescription

Current evidence suggests that long-term aspirin therapy may not be advisable for patients already on blood thinners. The trial indicated that combining aspirin with other medications raised the overall hazard ratio to 1.53, indicating that patients using aspirin were 30% more likely to experience adverse events.

AQUATIC Trial Findings

An article published in the New England Journal of Medicine on August 30, 2025, highlighted the results of the trial conducted by cardiologists in collaboration with the French Alliance for Cardiovascular Trials and the AQUATIC Trial Investigators. The study found no significant benefits for chronic coronary syndrome patients taking aspirin in addition to ongoing oral anticoagulation therapy six months or more post-stent placement.

Aspirin’s Historical Use and Risks

Traditionally, aspirin has been used as a long-term blood thinner alongside anti-platelet medications. However, the actual benefits have been debated, especially concerning the risk of major bleeding events. The trial, funded by the French Ministry of Health and Bayer Healthcare, sought to determine whether aspirin could improve outcomes for patients with chronic coronary syndrome as per the 2024 ESC Guidelines.

Trial Methodology and Results

The researchers conducted a randomized placebo-controlled trial comparing aspirin with anticoagulants against a placebo with anticoagulants. The study quickly revealed no additional benefits from aspirin. A total of 872 patients with chronic coronary syndrome, at least six months post-stent placement, were recruited and randomly assigned to two groups: one receiving 100 mg of aspirin daily along with their anticoagulants, and the other receiving a placebo that resembled aspirin.

Assessment of Outcomes

The primary objective was to assess the hazard ratios for various outcomes, including cardiovascular mortality over four years, thrombotic cardiovascular events (e.g., stroke, heart attack), and major bleeding incidents. The researchers sought to determine the increased likelihood of adverse events for patients taking aspirin alongside their standard medication.

Trial Conclusion and Ethical Considerations

Initially planned to last six years, the trial was terminated after just over two years due to clear differences in outcomes, which raised ethical concerns about continuing. The results showed that 58 participants in the aspirin group died (13.4%) compared to 37 (8.4%) in the placebo group, yielding a hazard ratio of 1.72 for aspirin. Additionally, the aspirin group experienced more major bleeding events, with 44 cases (10.2%) compared to 15 (3.4%) in the placebo group, resulting in a hazard ratio of 3.35.

Overall Findings

The comprehensive hazard ratio, which included all serious adverse outcomes, was calculated at 1.53, with 467 participants in the aspirin group reporting adverse events compared to 395 in the placebo group. The authors concluded that among patients with chronic coronary syndrome at high atherothrombotic risk receiving oral anticoagulation, the addition of aspirin was associated with a higher risk of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, acute limb ischemia, and major bleeding incidents.

References

Lemesle G, Didier R, Steg PG, et al. Aspirin in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation. New England Journal of Medicine. 2025;393(16):1578-1588. doi:10.1056/NEJMoa2507532

Vrints C, Andreotti F, Koskinas KC, et al. 2024 ESC Guidelines for the management of chronic coronary syndromes: Developed by the task force for the management of chronic coronary syndromes of the European Society of Cardiology (ESC) Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024;45(36):3415-3537. doi:10.1093/eurheartj/ehae177