Aspirin vs clopidogrel in chronic coronary syndromes: a meta-analysis of ethnic differences

Background and Aims Emerging data suggest that, in patients with chronic coronary syndromes (CCS), clopidogrel provides superior antithrombotic protection compared with aspirin for secondary prevention, without an associated increase in bleeding risk. The consistency of the observed benefits across ethnicities remains uncertain.Methods Randomized controlled trials (RCTs) comparing aspirin vs clopidogrel for secondary prevention in patients with CCS were screened. The primary endpoint was trial-defined major adverse cardiovascular events (MACE). Prespecified subgroup interaction by ethnicity (East Asian vs non-East Asian) was performed. Trial sequential analysis was used to assess the statistical power of the results.Results Seven RCTs were included, encompassing 30 165 patients, of whom 75.1% were East Asians. Median follow-up was 36.0 months. Overall, clopidogrel was associated with significant reductions in MACE (incidence rate ratio [IRR] 0.83, 95% confidence interval [CI] 0.69-0.99) and net adverse clinical events (IRR 0.83, 95% CI 0.69-0.99), compared with aspirin. There were no differences between groups in major bleeding, myocardial infarction, or mortality. The results were consistent in the East Asian population, whereas a significant interaction by ethnicity was observed for MACE (East Asians: IRR 0.76, 95% CI 0.59-0.98; non-East Asians: IRR 1.00, 95% CI 0.74-1.36; Pint = 0.010) and mortality (Pint = 0.014), with no significant benefits observed in non-East Asian patients. The analyses were statistically powered for most outcomes in East Asian populations but for none in non-East Asian populations.Conclusions In patients with CCS, the overall body of evidence suggests improved outcomes with clopidogrel compared with aspirin, without an apparent effect on mortality. However, a high level of confidence in these findings is currently limited to East Asian populations, and additional evidence is needed to clarify their applicability to non-East Asian patients.Study registration PROSPERO (CRD420251145176).