The optimal antithrombotic strategy for patients with chronic coronary syndrome (CCS) at high atherothrombotic risk who require long-term oral anticoagulation (OAC) has been a subject of clinical debate. The AQUATIC trial (NCT04217447) was designed to address this, but was stopped early due to an excess of deaths in the group receiving aspirin in addition to OAC.¹

This multicentre, double-blind, randomised, placebo-controlled trial was conducted in France. It enrolled 872 patients with CCS who had undergone stent implantation more than six months prior, were considered at high atherothrombotic risk, and were receiving long-term OAC.

Patients were randomised on a 1:1 basis to receive either aspirin (100 mg once daily) or a placebo, while continuing their existing OAC therapy. The primary efficacy outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI), stroke, systemic embolism, coronary revascularisation, or acute limb ischaemia. The key safety outcome was major bleeding.

The trial was terminated prematurely on the advice of the data and safety monitoring board after a median follow-up of 2.2 years.

A primary efficacy outcome event occurred in 73 patients (16.9%) in the aspirin group compared to 53 patients (12.1%) in the placebo group (adjusted hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.07 to 2.18; P=0.02).

Furthermore, death from any cause was significantly higher in the aspirin group, occurring in 58 patients (13.4%) versus 37 patients (8.4%) in the placebo group (adjusted HR, 1.72; 95% CI, 1.14 to 2.58; P=0.01). The risk of major bleeding was more than three times higher with aspirin, affecting 44 patients (10.2%) compared to 15 patients (3.4%) with placebo (adjusted HR, 3.35; 95% CI, 1.87 to 6.00; P<0.001).

Among patients with CCS at high atherothrombotic risk receiving an oral anticoagulant, the addition of aspirin led to a higher risk of the composite primary outcome than placebo. The findings from AQUATIC demonstrate that adding aspirin to OAC in this patient population results in significant harm, increasing not only major bleeding but also the risk of adverse ischaemic events and all-cause mortality. These results suggest that OAC monotherapy is the preferable strategy for these patients.²

This study was funded by the French Ministry of Health and Bayer Healthcare.

References

1. Lemesle G, Didier R, Steg PG, et al. Aspirin in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation. N Engl J Med 2025;393:1578-1588. https://doi.org/10.1056/NEJMoa2507532.

2. Parker WAE, Storey RF. AQUATIC findings sink antiplatelet therapy for patients with chronic coronary syndrome requiring oral anticoagulants. Nat Rev Cardiol. 2025. https://doi.org/10.1038/s41569-025-01224-0.

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