Ahmed Ibrahim, Basant E. Katamesh, Naiela E Almansouri, Imad SammanTahhan, Amer Af, Hossam Elbenawi, Pierre Sabouret, Giuseppe Andò
BACKGROUND: The optimal long-term antiplatelet monotherapy after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) remains uncertain, with limited data comparing aspirin and clopidogrel monotherapy. This meta-analysis aims to compare the safety and efficacy of clopidogrel versus aspirin in patients who have completed a standard duration (≥6 months) of event-free dual antiplatelet therapy (DAPT) following PCI with DES. METHODS: A comprehensive literature search was conducted across major electronic databases through May 2025 to identify relevant studies that compared clopidogrel monotherapy with aspirin monotherapy in adults who had undergone PCI with DES implantation. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE). Pooled estimates of relative risks (RRs) and adjusted hazard ratios (HRs) were calculated using a random-effects model. RESULTS: Five studies [two randomized controlled trials, three observational studies; n = 16, 289 patients] were included. Clopidogrel monotherapy was associated with a significant 31% reduction in MACCE compared with aspirin monotherapy [RR: 0.69; 95% confidence interval (CI) 0.60-0.79; P < 0.0001]. A pooled analysis of HRs demonstrated a similar benefit (HR: 0.67; 95% CI 0.58-0.77). Incidences of major bleeding and all-cause death were comparable between the two groups (RR: 0.93; 95% CI 0.57-1.51 and RR: 0.96; 95% CI 0.74-1.25, respectively). Notably, the analysis of HRs demonstrated that clopidogrel significantly reduced the risk of stroke (HR: 0.60; 95% CI 0.45-0.82; P = 0.001) and myocardial infarction (MI) (HR: 0.65; 95% CI 0.49-0.88; P = 0.005). CONCLUSION: Clopidogrel monotherapy is more effective than aspirin for long-term prevention of MACCE, MI, and stroke, without increasing the major bleeding risk. PROSPERO ID: CRD420251070685.