Clopidogrel Versus Aspirin Monotherapy in High-Risk Patients after Percutaneous Coronary Intervention (SMART-CHOICE 3): A Randomised, Open-Label, Multicentre Trial

Background: The optimal long-term antiplatelet regimen for patients undergoing percutaneous coronary intervention (PCI) remains controversial. This study aimed to compare the efficacy and safety of clopidogrel versus aspirin monotherapy in patients with remote PCI. Methods: In this multicentre, open-label, randomised trial, patients at high risk of recurrent ischaemic events (prior myocardial infarction [MI], medication-treated diabetes, or complex coronary artery lesions) who completed the standard duration of dual antiplatelet therapy (DAPT) after PCI were randomly assigned to receive clopidogrel or aspirin monotherapy at 26 sites in South Korea. The primary endpoint was a composite of death from any cause, MI, or stroke. Secondary endpoints included bleeding defined as Bleeding Academic Research Consortium type 2, 3 or 5. This trial is registered with ClinicalTrials.gov, NCT04418479. Findings: Between August 10, 2020, and July 31, 2023, we assigned 2752 patients to clopidogrel monotherapy and 2754 patients to aspirin monotherapy. During a median follow-up of 2·3 years (IQR 1·6–3·0), the primary endpoint occurred in 92 (4·4%) and 128 (6·6%) patients in the clopidogrel and aspirin groups (HR 0·71 [95% CI 0·54–0·93]; P=0·013). Death from any cause occurred in 50 (2·4%) and 70 (4·0%) patients in the clopidogrel and aspirin groups, respectively (HR 0·71 [95% CI 0·49–1·02]) and MI occurred in 23 (1·0%) and 42 (2·2%) patients in the clopidogrel and aspirin groups, respectively (HR 0·54 [95% CI 0·33–0·90]). There was no apparent difference between the clopidogrel and aspirin groups in the risk of bleeding (clopidogrel vs. aspirin, 3·0% vs. 3·0%; HR 0·97 [95% CI 0·67–1·42]). Interpretation: Among patients who were at high risk of recurrent ischaemic events and completed the standard duration of DAPT following PCI, clopidogrel monotherapy, compared with aspirin monotherapy, significantly reduced the composite of death from any cause, MI, or stroke without increasing bleeding.