Long-Term Clopidogrel versus Aspirin Monotherapy After Drug-Eluting Stent Implantation: A Nationwide Real-World Comparative Study

Lifelong antiplatelet maintenance therapy is required after drug-eluting stent (DES) implantation. Although recent randomized studies have suggested potential benefits of clopidogrel monotherapy over aspirin, evidence from unselected real-world populations remains limited. Using a randomly sampled 20% representative cohort from the Korean National Health Insurance Service database, we identified patients who underwent PCI with DES between 2002 and 2018. Among patients who remained event-free for 3 years after PCI, thereby defining a stable late chronic maintenance phase, treatment groups were defined by the prescribed antiplatelet agent within 30 days before event or censoring. After 1:1 propensity score matching, 18,168 patients were analyzed. The primary endpoint was a composite of all-cause death, myocardial infarction (MI), ischemic stroke, and major bleeding during follow-up of up to 10 years. Secondary endpoints comprised two composite outcomes: an ischemic composite (MI, repeated revascularization, ischemic stroke, and cardiovascular death) and a hemorrhagic composite (intracranial hemorrhage and major bleeding). The primary composite endpoint did not differ between clopidogrel and aspirin groups (adjusted hazard ratio HR 1.01, 95% confidence interval CI 0.94-1.09; P=0.85). Ischemic and hemorrhagic composite outcomes were also comparable (adjusted HR 0.94 0.84-1.05 and 1.03 0.92-1.14, respectively). No significant differences were observed in individual endpoints except for MI (adjusted HR 0.71 0.58-0.87; P=0.001), favoring clopidogrel. In conclusion, in this nationwide real-world cohort of event-free survivors three years after DES PCI, aspirin and clopidogrel showed comparable long-term efficacy and safety during the chronic maintenance phase over 10 years of follow-up, without broad net clinical advantage of either strategy.