• Adrienne N Dula, Michael Mlynash, Nathan D Zuck, Gregory W Albers, Steven J Warach, and DEFUSE 3 Investigators.
• From the Department of Neurology (A.N.D., N.D.Z., S.J.W.), Dell Medical School at The University of Texas, Austin.
• Stroke. 2020 Feb 1; 51 (2): 481-488.

AbstractBackground and Purpose- Clinical deficits from ischemic stroke are more severe in women, but the pathophysiological basis of this sex difference is unknown. Sex differences in core and penumbral volumes and their relation to outcome were assessed in this substudy of the DEFUSE 3 clinical trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). Methods- DEFUSE 3 randomized patients to thrombectomy or medical management who presented 6 to 16 hours from last known well with proximal middle cerebral artery or internal carotid artery occlusion and had target core and perfusion mismatch volumes on computed tomography or magnetic resonance imaging. Using univariate and adjusted regression models, the effect of sex was assessed on prerandomization measures of core, perfusion, and mismatch volumes and hypoperfusion intensity ratio, and on core volume growth using 24-hour scans. Results- All patients were included in the analysis (n=182) with 90 men and 92 women. There was no sex difference in the site of baseline arterial occlusion. Adjusted by age, baseline National Institutes of Health Stroke Scale, baseline modified Rankin Scale score, time to randomization, and imaging modality, women had smaller core, hypoperfusion, and penumbral volumes than men. Median (interquartile range) volumes for core were 8.0 mL (1.9-18.4) in women versus 12.6 mL (2.7-29.6) in men, for Tmax>6 seconds 89.0 mL (63.8-131.7) versus 133.9 mL (87.0-175.4), and for mismatch 82.1mL (53.8-112.8) versus 108.2 (64.1-149.2). The hypoperfusion intensity ratio was lower in women, 0.31 (0.15-0.46) versus 0.39 (0.26-0.57), P=0.006, indicating better collateral circulation, which was consistent with the observed slower ischemic core growth than men within the medical group (P=0.003). Conclusions- In the large vessel ischemic stroke cohort selected for DEFUSE 3, women had imaging evidence of better collateral circulation, smaller baseline core volumes, and slower ischemic core growth. These observations suggest sex differences in hemodynamic and temporal features of anterior circulation large artery occlusions. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02586415.

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