When more is worse: aspirin backfires in anticoagulated post-PCI patients

The optimal long-term antithrombotic regimen for patients with chronic coronary syndrome (CCS) who also require oral anticoagulation (OAC) has been a persistent clinical challenge, particularly for those with a history of percutaneous coronary intervention (PCI).1–4 While consensus documents and prior trials suggested that OAC monotherapy may be sufficient beyond the early post-PCI period, robust evidence in contemporary high-risk Western populations has been limited.1,5 The AQUATIC trial, presented at the European Society of Cardiology Congress 2025, directly addressed this clinical challenge.6 AQUATIC was a multi-centre, double-blind, placebo-controlled randomized trial conducted at 51 French centers.6 Eligible patients had CCS with prior stenting >6 months ago, an indication for long-term OAC, and at least one feature of high residual atherothrombotic risk, including diabetes, chronic kidney disease, complex PCI, multi-vessel disease, previous stent thrombosis, peripheral artery disease, or prior PCI for acute coronary syndrome. The trial was stopped early, after a median follow-up of 2.2 years, with 872 of the 2000 planned patients enrolled, due to excess mortality in the aspirin group.6 Patients were randomized to aspirin (100 mg daily) or placebo in addition to ongoing OAC (90% direct oral anticoagulants). At baseline, mean age and CHA2DS2-VASc score were 72 years and 4, respectively; 85% were male, and 68% were receiving concomitant antiplatelet monotherapy plus OAC. The median interval between PCI and enrolment was 3 years.6 The primary efficacy endpoint (a composite of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischaemia) occurred in 16.9% of patients receiving aspirin vs. 12.1% with placebo (adjusted hazard ratio [HR] 1.53; 95% CI 1.07–2.18; P = 0.02). All-cause death was significantly higher with aspirin (13.4% vs. 8.4%; adjusted HR 1.72; 95% CI 1.14–2.58; P = 0.01), largely driven by cardiovascular mortality; major bleeding was more than tripled (10.2% vs. 3.4%; adjusted HR 3.35; 95% CI 1.87–6.00; P < 0.001). Stent thrombosis was rare with only one event in each group.6 AQUATIC extends prior open-label evidence, mostly from Asian cohorts with lower ischaemic risk, by providing double-blind confirmation in a European, high-risk, post-PCI population.1,6 However, the trial has limitations, including premature termination with consequent loss of statistical power, restriction to a single-country setting, and underrepresentation of women. AQUATIC shows that OAC monotherapy represents the long-term antithrombotic ‘sweet spot’ in post-PCI patients with an indication for chronic anticoagulation, with addition of aspirin reserved for carefully selected, time-limited scenarios. The data underlying this article were taken from the quoted references.