Abstract Body: Background: Sex differences have been observed in functional outcomes after endovascular thrombectomy (EVT). Brain frailty markers like atrophy and small vessel disease burden have been shown to be associated with EVT outcomes. We aimed to investigate the association between imaging markers of brain frailty and functional outcomes after EVT in women and men.
Methods: This study is a post hoc analysis of the ESCAPE-NA1 trial that evaluated the efficacy and safety of nerinetide in patients with large vessel occlusion receiving EVT within 12 hours of onset. Baseline CT was used to assess brain frailty markers including atrophy score, inter-caudate distance to inner table width ratio [CC/IT ratio]), white matter disease (Fazekas score), presence of lacunes and old infarctions, and follow-up MRI was used to assess microbleed and lacunes burden. Outcomes included the modified Rankin Scale (mRS) at 90 days (dichotomized as 0-2 vs 3-6, and ordinal/shift analysis). Multivariable logistic regression models were used to examine the association between imaging frailty measures and 90-day mRS separately in women and men.
Results: A total of 1,102 participants (mean age 69.5 ± 13.7 years, 548 women) were analyzed. Women were older (74 vs. 69 years, p<0.0001), less likely to smoke (38% vs. 60%, p<0.0001), and had a lower baseline NIHSS (16 [12–21] vs. 17 [13–21], p=0.009), compared to men. Regarding imaging frailty measures, women had a lower CC/IT ratio (0.12 [0.09–0.15] vs. 0.13 [0.10–0.15], p=0.01), a higher Fazekas score (1 [0–2] vs. 0 [0–2], p<0.0001), and more frequent lacunes (27% vs. 22%, p=0.04). In the multivariable analyses, imaging frailty measures were generally associated with worse outcomes at 90-days; however, significant associations between these markers and 90-day mRS were observed only in women and not in men. CT-based markers such as cortical and subcortical atrophy, CC/IT ratio, old infarction carried significantly lower odds of 90-day mRS 0-2 in women but not men (Figure 1). Similar findings were also seen on shift analyses of the mRS. However, there were no statistically significant interactions by sex for these brain frailty measures.
Conclusion: In this cohort of EVT recipients, significant associations between imaging brain frailty measures and 90-day outcomes were seen only in women and not in men. These findings merit validation in other cohorts as they suggest sex differences in the effects of brain frailty on post-stroke outcomes.