August 30, 2025New England Journal of Medicine
Aspirin in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation
Gilles LemesleRomain DidierPhilippe Gabríel StegTabassome SimonGilles MontalescotNicolas DanchinChristophe BautersDidier BlanchardClaire BouletiDenis AngoulvantStéphane AndrieuGérald VanzettoMathieu KernéisVéronique DecalfÉtienne PuymiratDominique MottierAbdourahmane DialloÉric VicautMartine GilardGuillaume Cayla
Key Points
- Adding aspirin increased the risk of composite cardiovascular events compared to placebo.
- In the aspirin group, 16.9% experienced primary efficacy outcomes versus 12.1% in the placebo group.
- Overall mortality was significantly higher in the aspirin group at 13.4% versus 8.4% for placebo.
- Major bleeding occurred more frequently in the aspirin group, at 10.2%, compared to 3.4% in placebo.
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Among patients with CCS at high atherothrombotic risk who require OAC therapy, aspirin significantly increased the risk of major cardiovascular events, all-cause mortality and major bleeding, and its use should be discouraged. Other studies have investigated antithrombotic therapy for stable coronary artery disease and AF, but this is the first randomized trial to include patients who had prior stenting and with high atherothrombotic risk − event rates were around seven times higher in AQUATIC than in previous trials. Our findings can now be considered in future ESC Guidelines to build on current recommendations, which are based on expert consensus.”
“Stented patients on oral anticoagulation should not receive long-term aspirin even if they are at high atherothrombotic risk.”
“We as clinicians are difficult to change. If patients are doing well and they're on an oral anticoagulant plus an aspirin because [their physicians are] worried about the stent, they just keep them on it. We see this over and over again in every single thing—it just takes time to change a clinician's behavior of how they're prescribing medicine and how they're viewing the data.”
Implication
Randomized trial shows increased cardiovascular events in patients with chronic coronary syndrome, highlighting aspirin's risks alongside oral anticoagulation.
Abstract
The appropriate antithrombotic regimen for patients with chronic coronary syndrome who are at high atherothrombotic risk and receiving long-term oral anticoagulation remains unknown. We conducted a multicenter, double-blind, randomized, placebo-controlled trial in France involving patients with chronic coronary syndrome who had undergone a previous stent implantation (>6 months before enrollment) and were at high atherothrombotic risk and currently receiving long-term oral anticoagulation. The patients were randomly assigned in a 1:1 ratio to receive aspirin (100 mg once daily) or placebo; all the patients continued to receive their current oral anticoagulation therapy. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia. The key safety outcome was major bleeding. A total of 872 patients underwent randomization; 433 were assigned to the aspirin group, and 439 to the placebo group. The trial was stopped early at the advice of the independent data and safety monitoring board after a median follow-up of 2.2 years because of an excess of deaths from any cause in the aspirin group. A primary efficacy outcome event occurred in 73 patients (16.9%) in the aspirin group and in 53 patients (12.1%) in the placebo group (adjusted hazard ratio, 1.53; 95% confidence interval [CI], 1.07 to 2.18; P = 0.02). Death from any cause occurred in 58 patients (13.4%) in the aspirin group and in 37 (8.4%) in the placebo group (adjusted hazard ratio, 1.72; 95% CI, 1.14 to 2.58; P = 0.01). Major bleeding occurred in 44 patients (10.2%) in the aspirin group and in 15 patients (3.4%) in the placebo group (adjusted hazard ratio, 3.35; 95% CI, 1.87 to 6.00; P<0.001). A total of 467 and 395 serious adverse events were reported in the aspirin group and placebo group, respectively. 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. (Funded by the French Ministry of Health and Bayer Healthcare; ClinicalTrials.gov number, NCT04217447.).
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Cite This Study
Lemesle et al. (2025) studied this question.