Clopidogrel Vs Aspirin Monotherapy for Secondary Prevention After Percutaneous Coronary Intervention A Nationwide Cohort Study

Background After guideline-recommended dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI), long-term antiplatelet monotherapy is advised, but the optimal agent in real-world practice remains uncertain. Objectives The authors aimed to compare efficacy and safety of clopidogrel versus aspirin monotherapy in stable post-PCI patients. Methods Using the Korean nationwide claims and health examination database, we identified PCI-treated patients maintained on clopidogrel or aspirin monotherapy between 2009 and 2019. The co-primary outcomes were major adverse cardiovascular events (a composite of cardiovascular death, myocardial infarction or ischemic stroke) and major bleeding. Results Among 133,454 patients receiving DAPT, 67,652 (50.7%) continued with clopidogrel monotherapy and 65,802 (49.3%) continued with aspirin monotherapy. The median durations of DAPT and monotherapy duration were 1.0 year (IQR: 0.8-1.2) and 3.3 years (IQR: 1.3-6.2), respectively. After stabilized inverse probability of treatment weighting, clopidogrel monotherapy was associated with lower risks of major adverse cardiovascular events (HR: 0.759; 95% CI: 0.733-0.785; P < 0.0001) and major bleeding (HR: 0.895; 95% CI: 0.848-0.945; P < 0.0001) compared with aspirin monotherapy. Clopidogrel monotherapy was associated with lower risks of cardiovascular death (HR: 0.605; 95% CI: 0.573-0.638; P < 0.0001), myocardial infarction (HR: 0.921; 95% CI: 0.877-0.968; P = 0.0011), and ischemic stroke (HR: 0.674; 95% CI: 0.624-0.729; P < 0.0001) than aspirin monotherapy. The treatment effects were consistent across prespecified subgroups and DAPT durations. Conclusions In the stable post-PCI period, clopidogrel monotherapy may be preferred over aspirin monotherapy for long-term prevention due to its efficacy and safety.