Efficacy and safety of clopidogrel and aspirin initiated within 72 hours after mild ischemic stroke or high-risk TIA by sex: a prespecified subgroup analysis of the INSPIRES trial

Background: Sex differences may influence outcomes of dual antiplatelet therapy after acute ischemic stroke or transient ischemic attack (TIA). We evaluated whether treatment effects of clopidogrel plus aspirin differ by sex in patients with mild ischemic stroke or high-risk TIA. Research design and methods: This prespecified subgroup analysis used data from the INSPIRES trial, a multicenter, double-blind, placebo-controlled randomized trial conducted in China. Patients aged 35–80 years enrolled within 72 hours of symptom onset were randomized to clopidogrel plus aspirin or aspirin alone. The primary efficacy outcome was new stroke within 90 days, and the primary safety outcome was moderate-to-severe bleeding. Sex-by-treatment interaction was assessed. Results: Among 6,100 patients (female 35.8%), new stroke occurred in 7.9% of females and 6.95% of males in the clopidogrel plus aspirin group, compared with 9.9% and 8.71% in the aspirin group, respectively. No significant sex-by-treatment interaction was observed for stroke prevention. Rates of moderate-to-severe bleeding were low and similar between females and males, with no evidence of interaction. Conclusions: In this prespecified subgroup analysis, clopidogrel plus aspirin showed no sex-based differences in efficacy or safety. These findings do not support sex-specific treatment effects. Trial registration: ClinicalTrials.gov (NCT03635749).