Clopidogrel monotherapy versus aspirin monotherapy in females and males after percutaneous coronary intervention: a sex-stratified analysis of the SMART-CHOICE 3 trial.

Background

Clopidogrel has emerged as a promising alternative to aspirin monotherapy for maintenance therapy after percutaneous coronary intervention (PCI); however, the optimal antiplatelet strategy according to sex remains controversial.

Aims

We aimed to investigate whether the treatment effect of antiplatelet therapy differs according to sex.

Methods

This study was a prespecified substudy of the SMART-CHOICE 3 trial. Patients at high risk of recurrent ischaemic events who had completed the standard duration of dual antiplatelet therapy after PCI were randomly assigned to receive clopidogrel or aspirin monotherapy. The primary endpoint was a composite of all-cause death, myocardial infarction, or stroke.

Results

A total of 5,506 patients, including 1,002 females and 4,504 males, were enrolled in South Korea. Females had a higher risk profile than males; however, the incidence of the primary endpoint did not differ significantly between females and males (6.7% vs 5.2%, adjusted hazard ratio [HR] 0.89, 95% confidence interval [CI]: 0.62-1.28; p=0.537). Clopidogrel, compared with aspirin, significantly reduced the primary endpoint in females (4.3% vs 9.4%, adjusted HR 0.45, 95% CI: 0.24-0.85; p=0.014) but not in males (4.4% vs 6.0%, adjusted HR 0.77, 95% CI: 0.56-1.07; p=0.116). There was no significant interaction between sex and the antiplatelet therapy (p for interaction=0.288).

Conclusions

In patients with remote PCI and a high risk of recurrent ischaemic events, 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. No significant sex-by-treatment interaction was observed, supporting the consistency of the treatment effect across sexes.