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.

Summary

Among 5,506 high-risk post-PCI patients who had completed standard DAPT, clopidogrel monotherapy reduced the composite of death, MI, or stroke versus aspirin (3‑year KM 4.4% vs 6.6%; HR 0.71) without increasing bleeding (3.0% vs 3.0%). Benefits were consistent across components (notably lower MI) and achieved with similar dosing and tolerability.

Key Findings

• Primary composite endpoint lower with clopidogrel vs aspirin (3‑year 4.4% vs 6.6%; HR 0.71, p=0.013).
• No difference in major bleeding between clopidogrel and aspirin (3.0% vs 3.0% at 3 years).
• Reductions observed in MI (HR 0.54) with similar dosing and tolerability across groups.

Clinical Implications

For high-risk patients post-PCI who have completed guideline‑recommended DAPT, clopidogrel monotherapy can be considered over aspirin to reduce death/MI/stroke without added bleeding; implementation should consider local genotypes/drug interactions and guideline updates.

Limitations

• Open-label design may introduce performance bias
• Single‑country (South Korea) limits generalizability and pharmacogenomic diversity

Future Directions

Head-to-head comparisons in broader populations, genotype-guided antiplatelet strategies, and cost‑effectiveness analyses to inform global guidelines.