SMART-CHOICE 3 | Efficacy and Safety of Clopidogrel vs Aspirin Monotherapy in High Risk Patients after Percutaneous Coronary Intervention

Courtesy of Dr. Juan Manuel Pérez.

After post percutaneous coronary intervention (PCI) standard duration dual antiplatelet therapy (DAPT), the optimal long term monotherapy strategy is yet to be defined. The SMART-CHOICE 3 clinical trial was designed to assess whether clopidogrel monotherapy is superior to aspirin in terms of efficacy and safety in high risk patients after PCI. 

This was a randomized, open, multicenter study carried out in 26 centers across South Korea between August 2020 and July 2023. After mean 17.5 month DAPT (RIC: 12.6–36.1), 2,752 patients were randomized to clopidogrel and 2,754 to aspirin.

Mean patient age was 65.2 ± 10.2 years and 79.3% were men. The most prevalent risk factors were dyslipidemia (66.6%), hypertension (62.6%), diabetes (37.8%) and smoking (59%). Left ventricular ejection fraction (LVEF) was 59.5 ± 9.7%, and 46.2% presented a history of acute myocardial infarction (AMI). 54.6% had multivessel disease, 2.7% a history of high digestive bleeding, and 3.9% a history of stroke (ACV). PCI was done in 76% of cases in the context of AMI (unstable angina 29%, NSTEMI 24–25%, STEMI 22%) and in 24% for chronic coronary syndrome. Anticoagulated patients were excluded. As part of prior DAPT, 67.1% had received clopidogrel, 32,5% Ticagrelor and 0,4% Prasugrel.

Primary end point was 3-year incidence of the combination of all cause death, AMI or stroke. Secondary end points included each separate primary end components, major bleeding (BARC 3 or 5), gastrointestinal complications and other clinically relevant events. 

Followed up to mean 2.3 years (RIC: 1,6–3,0), the primary outcome was seen in 92 (4.4%) clopidogrel patients and 128 (6.6%) aspirin patients (HR 0,71; p = 0,013).

Read also: RACE Trial: Effect of Balloon Pulmonary Angioplasty and Riociguat on Right Ventricular Afterload and Function in Chronic Thromboembolic Pulmonary Hypertension.

All-cause death occurred in 50 clopidogrel (2.4%) vs 70 (4.0%) aspirin patients (HR 0.71 [0,49–1,02]); AMI in 23 vs 42 (1.0% vs 2.2%; HR 0,54 [0,33–0,90]) and stroke in 23 vs 29 patients (1.3% vs 1.3%; HR 0.79 [0.46–1.36]). There were no differences in bleeding risk (3.0% in both groups; HR 0.97 [0.67–1.42]), and use of clopidogrel was not associated with higher incidence of adverse events vs aspirin.

To conclude, in patients at high ischemic risk completing DAPT after PCI, clopidogrel monotherapy reduced death, AMI and stroke risk vs aspirin, with no increased bleeding risk, which is why it should be considered the preferred choice for long term maintenance treatment. 

Original Title: Efficacy and Safety of Clopidogrel Versus Aspirin Monotherapy in Patients at High Risk of Subsequent Cardiovascular Events After Percutaneous Coronary Intervention (SMART-CHOICE 3).

Reference: Ki Hong Choi et al. The Lancet, Publicado online 30 de marzo de 2025. doi:10.1016/S0140-6736(25)00449-0.


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