Aspirin dosing after acute coronary syndrome with suspected aspirin resistance: the ANDAMAN trial

Background and Aims Despite current antithrombotic treatments, the recurrence of ischaemic events remains high in patients with diabetes mellitus (DM) or aspirin resistance after acute coronary syndrome (ACS). Whether twice-daily aspirin dosing reduces major adverse cardiovascular events (MACE) in this population remains unknown. Methods In this prospective multicentre, randomized trial, patients with ACS and DM or high-risk of aspirin resistance (HRAR) defined as: (i) an index event occurring while on aspirin; (ii) body mass index ≥27 kg/m2; or (iii) increased waist circumference were assigned to receive enteric-coated aspirin once daily (100 mg/day) or twice daily (100 mg morning and evening). The primary outcome was MACE, a composite of any death, myocardial infarction, stroke, urgent coronary revascularization, stent thrombosis, or acute arterial thrombotic event assessed using a time-to-first-event analysis. The main secondary outcome was major bleeding (Bleeding Academic Research Consortium type 3–5). Results In total, 2484 participants were enrolled (77.2% with DM, 55.5% with ST-elevation segment myocardial infarction). The median follow-up duration was 18 (interquartile range: 17.6–18.3) months. The primary outcome occurred in 95 of 1228 participants (7.7%) in the twice-daily aspirin group, and 110 of 1256 (8.8%) in the once-daily group (hazard ratio [HR] 0.90; 95% confidence interval [CI] 0.69–1.19; P = .42). Major bleeding rates were similar between the groups (1.9% vs 2.1%; HR 0.88; 95% CI 0.50–1.55). Conclusions In patients with ACS and DM or HRAR, twice-daily aspirin did not significantly reduce the risk of MACE compared to once-daily dosing. No significant difference was observed in major bleeding between groups. Trial Registration NCT02520921/EUDRACT No: 2015-000947-18.