Clopidogrel monotherapy versus aspirin monotherapy in females and males after percutaneous coronary intervention: a sex-stratified analysis of the SMART-CHOICE 3 trial.
Kwon W, Choi K, et al. • EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology • 2026
Clopidogrel monotherapy showed a directionally consistent reduction in the composite endpoint of all-cause death, myocardial infarction, or stroke compared with aspirin in both females and males after PCI, with no significant sex-by-treatment interaction observed.
Key Findings
Methods
The study enrolled 5,506 patients after PCI, of whom 1,002 were female and 4,504 were male, all at high risk of recurrent ischaemic events.
All patients had completed the standard duration of dual antiplatelet therapy after percutaneous coronary intervention (PCI) before randomization.
Patients were randomly assigned to receive clopidogrel or aspirin monotherapy.
The study was conducted in South Korea as a prespecified substudy of the SMART-CHOICE 3 trial.
Females comprised approximately 18.2% of the total study population.
Results
Females had a higher risk profile than males in this study population.
Despite a higher risk profile, the incidence of the primary endpoint did not differ significantly between females and males (6.7% vs 5.2%).
The adjusted hazard ratio for the primary endpoint in females versus males was 0.89 (95% CI: 0.62–1.28; p=0.537).
The primary endpoint was a composite of all-cause death, myocardial infarction, or stroke.
Results
Clopidogrel monotherapy significantly reduced the primary composite endpoint compared with aspirin in females but not in males.
In females, the primary endpoint occurred in 4.3% on clopidogrel versus 9.4% on aspirin (adjusted HR 0.45, 95% CI: 0.24–0.85; p=0.014).
In males, the primary endpoint occurred in 4.4% on clopidogrel versus 6.0% on aspirin (adjusted HR 0.77, 95% CI: 0.56–1.07; p=0.116).
The reduction in females represented approximately a 55% relative risk reduction with clopidogrel versus aspirin.
The direction of effect favored clopidogrel in both sexes, but statistical significance was only achieved in females.
Results
No significant interaction between sex and antiplatelet therapy was observed.
The p-value for the sex-by-treatment interaction was 0.288, indicating no statistically significant interaction.
The authors state this finding supports "the consistency of the treatment effect across sexes."
Despite numerically larger effect sizes in females, the lack of significant interaction suggests the difference in point estimates may be due to chance or statistical power limitations.
Conclusions
Clopidogrel monotherapy showed a directionally consistent reduction in ischaemic events compared with aspirin in both sexes among patients with remote PCI and high ischaemic risk.
The study population specifically consisted of patients who had completed standard dual antiplatelet therapy and were at high risk of recurrent ischaemic events.
The consistent directional benefit of clopidogrel over aspirin was observed across both female and male subgroups.
The authors conclude that the findings support consistency of the treatment effect across sexes despite the numerically larger point estimate in females.
The optimal antiplatelet strategy according to sex was described as "controversial" prior to this analysis.
What This Means
This research examined whether the choice of antiplatelet medication — clopidogrel versus aspirin — after a heart procedure called percutaneous coronary intervention (PCI, commonly known as stenting) has different effects in women versus men. The study analyzed data from 5,506 patients in South Korea who had already completed an initial period of taking two blood-thinning medications together, and were then switched to just one medication — either clopidogrel or aspirin — to prevent future heart attacks, strokes, or death. About 18% of patients were women, and women in the study tended to have more health risk factors than men.
The results showed that clopidogrel reduced the combined risk of death, heart attack, or stroke compared to aspirin in both women and men, but the reduction was statistically significant only in women (4.3% vs. 9.4% event rates, roughly a 55% relative reduction). In men, the trend also favored clopidogrel (4.4% vs. 6.0%) but did not reach statistical significance. Importantly, formal statistical testing found no significant difference in how clopidogrel and aspirin compared between women and men — meaning the data do not conclusively prove that one sex responds differently to the two drugs than the other.
This research suggests that clopidogrel monotherapy may be a beneficial alternative to aspirin for maintenance therapy after coronary stenting in both women and men at high ischaemic risk. The larger apparent benefit in women warrants further investigation, but given the lack of a statistically significant sex-by-treatment interaction, the current evidence supports applying the findings similarly across sexes rather than recommending different strategies for women versus men based on this study alone.
Kwon W, Choi K, Park Y, Jeong J, Kim C, Yun K, et al.. (2026). Clopidogrel monotherapy versus aspirin monotherapy in females and males after percutaneous coronary intervention: a sex-stratified analysis of the SMART-CHOICE 3 trial.. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. https://doi.org/10.4244/EIJ-D-26-00332