Joanna Mulvaney PhD , 2025-10-28 14:00:00
A French clinical trial designed to test whether long-term treatment with aspirin is necessary for patients with chronic coronary syndrome has been terminated, as the harms to participants out weighed the benefits of continuing the trial.
Some heart specialists have previously raised concerns that adding aspirin on top of other medications could be doing more harm than good. Prompting French clinicians to put aspirin through its safety paces. So should we be prescribing aspirin long-term? It seems that if patients are already using blood thinners, the answer is “no”. Adding aspirin on top of another drug increased overall hazard ratio to 1.53 with patients using aspirin being 30% more likely to suffer an adverse event.
Aquatic Investigators
In a NEJM research article published on August 30, 2025, cardiologists from across France worked with the French Alliance for Cardiovascular Trials, Paris and the AQUATIC Trial Investigators announced that they had found no benefit to chronic coronary syndrome patients taking aspirin in addition to receiving continuing oral anticoagulation six months or more after having a stent fitted.
Aspirin has historically been used as a long-term blood thinner in addition to anti-platelet medications as a matter of routine; however, whether it actually helps has long been under discussion. Experts have expressed concern over the risk of major bleeding incidents. In the trial, sponsored by the French Ministry of Health and Bayer Healthcare, doctors examined whether aspirin improved outcomes for patients with chronic coronary syndrome (CCS) if used as advised by the 2024 ESC Guidelines.
Testing Aspirin’s Safety
The team performed a randomized placebo controlled clinical trial testing aspirin with anticoagulants against a placebo with anticoagulants and found very quickly that there was no benefit to adding aspirin to the mix. Medics recruited 872 patients living with CCS at least six months after having a stent fitted. The participants were randomized and split into two groups of 433 and 439. Doctors prescribed the first group 100 mg once daily aspirin in addition to their regular anticoagulants, and the second group was given a placebo in a format that looked identical to aspirin along with their usual anticoagulants.
Researchers aimed to determine the hazard ratios of various outcomes, including cardiovascular mortality within four years; thrombotic cardiovascular events-e.g. stroke, heart attack; occurrence of major bleeding events. How much more likely are people to die, have a heart attack/stroke or a bleeding event if they take aspirin on top of their regular medicine as opposed to just using their regular medicine?
Was Aspirin more a help or a harm?
This trial was intended to last six years (72 months); however, after just over two years, the researchers terminated the trial because the differences in outcomes were so clear that it was unethical to continue. In two years, 58 of the aspirin group had died (13.4%) vs 37 (8.4%) of the placebo group, with a hazard ratio of 1.72 for aspirin. Patients in the aspirin group were also more likely to experience a major bleeding event: 44 cases, or 10.2% of participants, while only 15 patients (3.4%) in the placebo group did. The hazard ratio was calculated as 3.35.
The overall hazard ratio, including all serious adverse outcomes tested, was 1.53, with 467 aspirin group participants reporting an adverse event versus 395 members off the placebo group.
The authors of the research paper conclude that: ‘among patients with chronic coronary syndrome at high atherothrombotic risk who were receiving an oral anticoagulant, the addition of aspirin led to a higher risk of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia than placebo, as well as higher risks of death from any cause and major bleeding.’
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
