Clopidogrel Versus Aspirin Monotherapy According to Atherothrombotic Risk Profile

BACKGROUND: Clopidogrel monotherapy has shown superior efficacy compared with aspirin after completion of dual antiplatelet therapy following percutaneous coronary intervention (PCI). However, whether treatment effects differ according to overall atherothrombotic risk integrating clinical and angiographic factors remains unclear. METHODS: This post hoc analysis of the SMART-CHOICE 3 (Smart Angioplasty Research Team: Choice of Optimal Anti-Thrombotic Strategy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents 3) randomized trial included patients who completed guideline-directed dual antiplatelet therapy after PCI. Atherothrombotic risk was defined using the a Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention and complex PCI. Patients with Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention ≥3 or complex PCI were classified as higher risk, and those with a Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention <3 without complex PCI were classified as lower risk. The primary end point was major adverse cardiac and cerebrovascular events (death, myocardial infarction, or stroke). Bleeding was defined as Bleeding Academic Research Consortium type 2, 3, or 5. RESULTS: Among 5506 patients, 4486 (81.5%) were at higher risk and 1020 (18.5%) were at lower risk. Over a median 2.3 years, the incidence of major adverse cardiac and cerebrovascular events was higher in the higher-risk group (6.1% versus 3.1%; hazard ratio, 1.83 [95% CI, 1.17–2.78]; P =0.007). In higher-risk patients, clopidogrel reduced major adverse cardiac and cerebrovascular events compared with aspirin (4.6% versus 7.4%; hazard ratio, 0.67 [95% CI, 0.50–0.89]; P =0.006), with no difference in lower-risk patients (3.0% versus 3.2%; hazard ratio, 1.03; P =0.945; interaction P =0.242). Bleeding was similar between groups. CONCLUSIONS: After completion of dual antiplatelet therapy following PCI, clopidogrel monotherapy was associated with lower ischemic risk than aspirin in patients with higher atherothrombotic risk, without increased bleeding. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04418479.