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-related differences may influence the efficacy and safety of dual antiplatelet therapy after acute ischemic stroke or transient ischemic attack (TIA). We assessed whether treatment effects of clopidogrel plus aspirin initiated within 72 hours differ by sex in patients with acute 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, 2 × 2 factorial randomized clinical trial conducted in 222 hospitals in China (2018-2022). Patients aged 35-80 years enrolled within 72 hours of symptom onset were randomized to receive clopidogrel plus aspirin or aspirin alone. The primary efficacy outcome was any new stroke within 90 days, and the primary safety outcome was moderate-to-severe bleeding. Treatment effects were assessed by sex and tested for interaction. RESULTS: Among 6,100 patients (median age 65 years; 35.8% women), the incidence of new stroke was 7.9% in women receiving clopidogrel plus aspirin versus 9.9% with aspirin alone, and 6.95% versus 8.71% in men, respectively. No significant treatment-by-sex interaction was observed for the primary efficacy outcome. Rates of moderate-to-severe bleeding were low and similar between sexes, with no evidence of a sex-based interaction. CONCLUSIONS: In this prespecified subgroup analysis, we found no evidence of a sex-based interaction in the efficacy or safety of clopidogrel plus aspirin initiated within 72 hours after mild ischemic stroke or high-risk TIA. These findings do not support sex-specific differences in treatment effect, although limited event numbers should be considered.