Efficacy of clopidogrel monotherapy versus aspirin monotherapy after percutaneous coronary intervention

Following percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) is standard to reduce thrombotic complications. However, the optimal monotherapy after DAPT remains debated. Clopidogrel may offer better protection than aspirin. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing clopidogrel versus aspirin monotherapy after DAPT in PCI patients. Searches were performed in MEDLINE, Embase, Scopus, CENTRAL, and ClinicalTrials.gov up to April 12, 2025. Outcomes included stroke, myocardial infarction (MI), all-cause mortality, and cardiovascular (CV) death. Hazard ratios (HRs) were pooled using random-effects models. Four RCTs comprising 19,554 patients (clopidogrel: 9,846; aspirin: 9,708) were included. Clopidogrel was associated with a significantly lower risk of stroke (HR: 0.69; 95% CI: 0.51-0.94; p = 0.02; I² = 28%) and MI (HR: 0.71; 95% CI: 0.51-0.99; p = 0.05; I² = 48%) compared with aspirin. There was no significant difference between clopidogrel and aspirin in terms of all-cause mortality (HR: 0.99; 95% CI: 0.78-1.25; p = 0.92; I² = 55%), CV death (HR: 0.87; 95% CI: 0.70-1.08; p = 0.22; I² = 0%), coronary revascularization (HR: 0.95; 95% CI: 0.83-1.09; p = 0.44; I² = 0%), major bleeding (HR: 0.97; 95% CI: 0.70-1.35; p = 0.87; I² = 57%), or stent thrombosis (HR: 0.66; 95% CI: 0.38-1.15; p = 0.15; I² = 0%). Clopidogrel monotherapy post-DAPT after PCI reduces stroke and MI risk compared to aspirin, without increasing mortality or bleeding. These findings support clopidogrel as a favorable alternative for monotherapy.