A major international cardiology study halted early due to safety concerns casts doubt on a common practice of prescribing aspirin to heart patients already on blood thinners. Teh French-led AQUATIC trial found that adding daily aspirin to existing anticoagulant therapy substantially increased the risk of both bleeding and cardiovascular events, including death, in patients with chronic coronary syndrome. Published this week in the New England Journal of Medicine, the findings suggest a need to reassess routine dual antiplatelet and anticoagulant regimens for these high-risk individuals.
For patients with chronic coronary syndrome who are already taking blood thinners, adding daily aspirin may increase the risk of cardiovascular events and death, a recent French study has found. The research challenges common practices in preventing secondary heart problems and highlights the need for a more cautious approach to combining antiplatelet and anticoagulant medications.
The study, conducted by researchers in France, involved 872 patients with chronic coronary syndrome who had previously received a stent and were already on long-term oral anticoagulation therapy. Participants were randomly assigned to receive either 100mg of aspirin daily or a placebo, while continuing their usual anticoagulant medication.
Researchers were looking at a combined endpoint of cardiovascular death, heart attack, stroke, systemic embolism, the need for repeat procedures to open blocked arteries, or acute limb ischemia. The primary safety concern was major bleeding.
Study Stopped Early Due to Increased Risk
The trial was halted prematurely after a median follow-up of 2.2 years, following a recommendation from an independent data and safety monitoring committee. This decision was prompted by a higher rate of all-cause mortality observed in the aspirin group.
Results showed that 73 patients (16.9%) in the aspirin group experienced the primary efficacy endpoint, compared to 53 patients (12.1%) in the placebo group – a relative risk of 1.53 (95% confidence interval: 1.07 to 2.18; p = 0.02). Overall mortality was also significantly higher in the aspirin group, with 58 deaths (13.4%) versus 37 deaths (8.4%) in the placebo group (relative risk = 1.72 [1.14 to 2.58]; p = 0.01). Major bleeding events were also more frequent in the aspirin group, occurring in 44 patients (10.2%) compared to 15 patients (3.4%) in the placebo group (relative risk = 3.35 [1.87 to 6.00]; p < 0.001). A total of 467 and 395 serious adverse events were reported in the aspirin and placebo groups, respectively.
Findings Offer New Insights into Secondary Prevention
The French study, known as AQUATIC 1, provides important new evidence regarding secondary prevention strategies for patients with a history of coronary syndrome. The findings suggest that routinely combining oral anticoagulants (90% of which were direct oral anticoagulants and 10% were vitamin K antagonists) with aspirin may be harmful. The study demonstrated a 50% to 70% increase in cardiovascular events and overall mortality, along with a 335% increase in major bleeding.
Approximately 37.4% of the study participants had type 2 diabetes. Researchers did not find a clear difference in the effect of aspirin based on diabetes status, suggesting the negative outcomes – increased events, mortality, and bleeding – were consistent across the high-risk population.
The study’s relatively short duration, with a follow-up period of around 18 to 24 months, is a noted limitation.
The researchers emphasize the importance of minimizing unnecessary treatments. Currently, most patients with stable coronary artery disease who require full-dose anticoagulation do not receive aspirin or other antiplatelet therapy. The findings suggest that dual antithrombotic therapy – using both an anticoagulant and an antiplatelet drug – should now be considered a rare exception rather than the standard of care for patients at high risk of thrombotic events.
(1) Lemesle G, Didier R, Steg PG, Simon T, Montalescot G, Danchin N, et al. AQUATIC Trial Investigators. Aspirin in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation. N Engl J Med. 2025 Oct 23;393(16):1578-1588
