Coronary artery disease (CAD) remains a leading cause of morbidity and mortality globally, necessitating effective secondary prevention strategies. Clopidogrel and aspirin are widely used antiplatelet therapies, but their comparative efficacy and safety remain debated. This systematic review and individual patient data meta-analysis aimed to compare clopidogrel versus aspirin in preventing recurrent cardiovascular events in patients with established CAD.
We conducted a systematic review of randomized controlled trials (RCTs) comparing clopidogrel and aspirin for secondary prevention in CAD patients. Databases including PubMed, Embase, and Cochrane Library were searched up to July 2025. Individual patient data from eligible trials were pooled to assess primary outcomes (major adverse cardiovascular events, including myocardial infarction, stroke, or cardiovascular death) and secondary outcomes (bleeding events, all-cause mortality). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards models, adjusted for baseline characteristics.
Seven RCTs involving 32,145 patients were included. Clopidogrel significantly reduced the risk of major adverse cardiovascular events compared to aspirin (HR 0.89, 95% CI 0.82–0.97, p=0.008), driven primarily by a lower incidence of myocardial infarction (HR 0.85, 95% CI 0.76–0.95). No significant difference was observed in stroke (HR 0.92, 95% CI 0.81–1.04) or cardiovascular death (HR 0.94, 95% CI 0.85–1.03). Major bleeding rates were comparable between clopidogrel and aspirin (HR 1.02, 95% CI 0.90–1.15, p=0.73), though clopidogrel was associated with a slightly higher risk of minor bleeding (HR 1.12, 95% CI 1.01–1.24). All-cause mortality did not differ significantly (HR 0.97, 95% CI 0.89–1.06).
Clopidogrel offers a modest but significant reduction in major cardiovascular events compared to aspirin for secondary prevention in CAD patients, with a similar risk of major bleeding. These findings support clopidogrel as a preferred option in certain CAD populations, though individual patient factors should guide treatment decisions.
Source: https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-025-09010-6
