Sex-Related Difference in Outcomes of Remote Ischemic Conditioning for Symptomatic Intracranial Atherosclerotic Stenosis

Abstract

Remote ischemic conditioning (RIC) is a novel and promising therapeutic intervention for symptomatic intracranial atherosclerotic stenosis (sICAS). This study aimed to evaluate sex differences in stroke recurrence among patients with sICAS and assess the efficacy of RIC in the RICA (chronic remote ischemic conditioning in patients with symptomatic intracranial atherosclerotic stenosis) trial. The RICA trial was a multicenter, randomized clinical trial conducted across 84 stroke centers in China. Patients with sICAS were randomly assigned on a 1:1 ratio to receive either RIC intervention or sham RIC intervention once daily for 12 months. The primary endpoint was ischemic stroke recurrence. The median follow-up duration was 3.5 years. Of the 3,033 patients enrolled in the RICA trial, 1,079 (35.58%) were women. Female patients were generally older (mean [SD] age 62.9 [8.8] years versus 60 [9.2] years) and had a higher prevalence of hypertension, diabetes, and a higher body mass index than male patients. No significant difference was observed in ischemic stroke recurrence risk between female and male patients during a median follow-up of 3.5 years (20.5% versus 16.6%, adjusted hazard ratio, 1.18; [95% CI, 0.97 to 1.42]). However, RIC significantly reduced the risk of ischemic stroke recurrence in male patients, while no similar effect was observed in female patients (adjusted hazard ratio, 0.88; [95% CI, 0.58 to 1.32]; P for interaction = 0.379). No significant sex-based differences were observed in ischemic stroke recurrence among patients with sICAS over the 3.5-year follow-up period. RIC may have better therapeutic benefits for male patients with good compliance.

Fig. 1.

Association of sex with clinical outcomes in the intention-to-treat population. *Adjusted by age, body mass index, time from qualifying event to randomization, previous ischemic stroke, previous transient ischemic attack, previous myocardial infarction, systolic blood pressure, low-density lipoprotein cholesterol, fasting blood glucose, smoking status, symptomatic qualifying artery, and stenosis degree of qualifying artery.

Fig. 2.

Kaplan–Meier event curve for the primary endpoint and the composite secondary endpoint by sex in the per-protocol population. (A) Primary endpoint (ischemic stroke). (B) Composite secondary endpoint (stroke, transient ischemic attack, or myocardial infarction). RIC, remote ischemic conditioning; HR, hazard ratio.