Efficacy and Safety of Clopidogrel Versus Aspirin Monotherapy After Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Dual antiplatelet therapy is a standard treatment after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS), but the optimal monotherapy agent post-dual antiplatelet therapy remains unclear. Clopidogrel and aspirin are widely used, yet their comparative effectiveness and safety in this patient population have not been fully established. This systematic review and meta-analysis compared the efficacy and safety of clopidogrel and aspirin monotherapy following PCI in patients with ACS. A comprehensive search of PubMed, Embase, and Web of Science was conducted from inception to March 31, 2025. Randomized controlled trials (RCTs) comparing clopidogrel and aspirin monotherapy in adult ACS patients post-PCI were included. Primary outcomes were all-cause death, myocardial infarction (MI), and ischemic stroke. Secondary outcomes included target-vessel and target-lesion revascularization, cardiovascular and noncardiovascular death, and stent thrombosis. The risk of bias was assessed using the Cochrane RoB 2 tool, and the GRADE methodology was applied to evaluate the certainty of evidence. Three RCTs involving 16,056 patients (clopidogrel: 8103; aspirin: 7953) were included. Clopidogrel significantly reduced MI (risk ratio = 0.71; 95% confidence interval: 0.55–0.92; P = 0.01) and target-vessel revascularization (risk ratio = 0.77; 95% confidence interval: 0.60–0.97; P = 0.03). No significant differences were found in all-cause death, ischemic stroke, or other secondary outcomes. Sensitivity analysis suggested a potential reduction in noncardiovascular death favoring clopidogrel. Clopidogrel monotherapy after PCI may offer superior protection against MI and target-vessel revascularization compared with aspirin, with no increased risk of death or stroke.