Age-related efficacy of aspirin in secondary prevention of coronary artery disease: START-ANTIPLATELET registry and meta-analysis of randomized trials

BACKGROUND Aspirin is a standard therapy for secondary prevention in coronary artery disease, yet its antiplatelet effect varies and incomplete thromboxane-A₂ inhibition has been shown in older individuals. Because no age threshold currently guides treatment, we investigated whether aspirin efficacy differs across predefined age cut-off in patients with coronary artery disease. METHODS We analyzed data from START-ANTIPLATELET registry, a multicenter prospective registry of patients hospitalized for acute coronary syndrome and subsequently treated with at least one month of aspirin monotherapy. Patients were stratified by age ≥65 vs <65 years. The primary endpoint was major adverse cardiovascular events, evaluated using Kaplan-Meier estimates and multivariable Cox regression. A systematic review and meta-analysis were conducted to evaluate the effect of aspirin for secondary prevention in older versus younger adults. Pooled risk ratios with 95% confidence intervals were calculated using a random-effects model. RESULTS 410 patients were included in the registry, of whom 53.7% had ≥65 years. Patients aged ≥65 years exhibited a substantially higher incidence of major adverse cardiovascular events than younger patients, for an absolute increase of 5 events per 1,000 patient-months. Older age was associated with increased risk of major adverse cardiovascular events (hazard ratio 4.99, 95%CI 1.11-22.58) independently of other cardiovascular risk factors (hazard ratio 3.94, 95%CI 0.84-18.65). The meta-analysis of 58,394 participants from 19 trials confirmed the increased risk of major adverse cardiovascular events among older individuals receiving aspirin compared with younger patients (RR 1.43, 95%CI 1.16-1.76). CONCLUSION The efficacy of aspirin monotherapy for secondary coronary artery disease prevention is reduced in elderly patients from 65 years of age onward.