Key Points:
- Standard cardiology practice recommends aspirin monotherapy indefinitely after DAPT for prevention of cardiovascular events after PCI, but some data has suggested clopidogrel therapy may be a superior alternative
- The SMART-CHOICE 3 trial is the first large multicenter trial to evaluate clopidogrel versus aspirin monotherapy among 5000 patients in 26 sites across South Korea
- The study found a significant improvement in major adverse cardiovascular and cerebrovascular outcomes among clopidogrel versus aspirin with no significant increase in bleeding
- This trial has ramifications for chronic coronary disease management in high risk ischemic patients after standard DAPT post-PCI
In standard cardiology practice, it has been recommended to prescribe aspirin monotherapy indefinitely following dual anti platelet (DAPT) for prevention of cardiovascular events after percutaneous coronary intervention (PCI). However, clopidogrel has been proposed as a possibly superior alternative to aspirin. This has been formally recommended by the 2024 ESE guidelines for management of chronic coronary syndromes (CCS) with a Class 1A recommendation. Although the HOST-EXAM trial previously the groundwork for this recommendation, a trial with a sufficiently large sample size to compare competitive with aspirin has been needed, with higher risk patients that the previous trial.
The SMART-CHOICE 3 was a randomized multi centered trial at 26 sites in South Korea enrolling 5000 patients on DAPT at high risk of recurrent ischemic events after PCI with DES ClinicalTrials.gov (NCT04418479). Patients with standard DAPT duration at least 12 months for MI and at least 6 months for any other indication were randomized 1:1 with clopidogrel versus aspirin monotherapy. Notable exclusion criteria included long-term treatment with anticoagulation, DAPT for any reason other than CAD, use of single antiplatelet therapy at screening, contraindications to aspirin or clopidogrel, or pregnancy or breastfeeding. Participants were well balanced by multiple characteristics including age, sex, BMI, hypertension, dyslipidemia, chronic kidney disease, LV ejection fraction, bleeding risk, DAPT regimen, and medication at randomization. Results were presented at ACC 2025 with simultaneous publications in Lancet.
The trial found that the primary endpoint of major adverse cardiovascular and cerebrovascular event (MACCE), a composite of death from any cause, myocardial infarction, or stroke, what significantly reduced among the clopidogrel group versus the aspirin group – HR 0.71 (95% CI 0.54–0.93) – with an absolute risk reduction of 2.2% and number needed to treat of 45 patients. Clopidogrel demonstrated reduction in secondary outcome of MI: HR 0.54 (95% CI 0.33–0.90). Notably, clopidogrel did not show significant difference in bleeding risk: HR 0.97 (95% CI 0.67–1.42).
In conclusion, the Smart Choice 3 trial is a first large trial to demonstrate clopidogrel monotherapy compared with aspirin demonstrated a lower composite risk of death, MI, and stroke with no significant change in bleeding. Though this trial was limited to an exclusively Korean population, these results have ramifications for antiplatelet therapy across patients with CAD.
