Patients at high-risk for ischemic events after percutaneous coronary intervention (PCI) who take clopidogrel post-procedure have significantly better outcomes than patients who take aspirin, new data from the SMART-CHOICE 3 trial show. Joo-Yong Hahn, MD, PhD, from the Samsung Medical Center, Seoul, South Korea, presented these results on behalf of all SMART-CHOICE 3 investigators during a late-breaking clinical trial presentation on Sunday at the American College of Cardiology (ACC) Scientific Sessions 2025. Dual antiplatelet therapy (DAPT) is a common strategy to prevent ischemic events in patients who underwent PCI and received a drug-eluting stent (DES). Data is lacking on the best long-term management strategies with the use of antiplatelet therapy in this patient population. The SMART-CHOICE 3 (Smart Angioplasty Research Team: Choice of Optimal Anti-Thrombotic Strategy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents) was a large, open-label, randomized trial that examined patients 19 years of age or older who were at risk for recurring ischemic events who completed DAPT after PCI. Patients were randomized 1:1 to receive clopidogrel or aspirin (75 mg vs 100 mg) orally once per day at 26 sites across South Korea. The median time between the procedure and randomization was 17.5 months. Incidence of a composite of all-cause death, myocardial infarction (MI) or stroke was the primary endpoint assessed in this intention-to-treat population. A total of 5,506 patients were randomly assigned to receive clopidogrel (n=2,752) or aspirin (2,754) monotherapy between August 10, 2020, and July 31, 2023. Throughout the mean follow-up time of 2.3 years, 92 patients in the clopidogrel group and 128 patients in the aspirin group experienced the primary endpoint (Kaplan Meier estimated at 3-years 4.4% [clopidogrel] versus 6.6% [aspirin]; hazard ratio [HR]=0.71, 95% confidence interval [CI]=0.54-0.93; p=0.013). Death occurred in 50 clopidogrel patients and 70 aspirin patients (2·4% [1.6–3.1] vs 4·0% [2.9–5.0] at 3 years; HR=0.71, 95% CI=0.49-1.02), MI in 23 clopidogrel patients and 42 aspirin patients (1.0% [0.6–1.4] vs 2.2% [1.4–2.9] at 3 years; HR=0.54, 95% CI=0.33-0.90) and stroke in 23 clopidogrel patients and 29 aspirin patients (1.3% [0·7–2.0] vs 1·3% [0.8–1.7] at 3 years; HR=0.79, 95% CI=0.46-1.36). Patients taking clopidogrel had the same risk of bleeding as patients taking aspirin (3.0% [2.0–3.9] vs 3.0% [2.2–3.9] at 3 years; HR=0.97, 95% CI=0.67–1.42). No adverse event differences were observed between the two groups. Overall, patients who were at a high risk for ischemic events who took clopidogrel had significantly reduced rates of all-cause death, MI and stroke, compared with patients who took aspirin, after PCI. No increased bleeding risk was observed in the clopidogrel versus aspirin groups. “In our study, clopidogrel beat aspirin as a lifelong maintenance monotherapy after standard-duration dual antiplatelet therapy,” said Dr. Hahn in a press release on Sunday. “Based on these results, I hope that guidelines will address clopidogrel monotherapy as comparable to aspirin monotherapy or as preferred to aspirin monotherapy for patients at high risk of recurrent ischemic events.” This study was sponsored by Dong-A ST Co. Source: Choi KH, Park YH, Lee J-Y, et al. Efficacy and safety of clopidogrel versus aspirin monotherapy in patients at high risk of subsequent cardiovascular event after percutaneous coronary intervention (SMART-CHOICE 3): a randomised, open-label, multicentre trial. Lancet. 2025 March 30 (Article in press). Image Credit: Screenshot by Bailey G. Salimes. Image Caption: Joo-Yong Hahn, MD, PhD, presents during a press conference on Sunday at the American College of Cardiology (ACC) Scientific Sessions 2025.