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Paradox for Women Emerges in Imaging of Ischemic Stroke

LOS ANGELES — Although women appear to have more favorable vascular and hemodynamic measures after an ischemic stroke than men, overall, they experience worse functional outcomes, new evidence demonstrates. The findings suggest other factors may be driving this inconsistency.

Women “had smaller penumbra, better collaterals and slower lesion growth, but still, paradoxically, had worse outcomes than men” at 90 days, Steven Warach, MD, PhD, said here at the 2020 International Stroke Conference (ISC).

“This even held true among those who achieved satisfactory recanalization,” he added.

Results also were published online in the February 2020 issue of Stroke.

Stroke Strikes Differently

Sex differences in ischemic stroke are well known, said Warach, Professor of Neurology at the University of Texas at Austin Dell Medical School. “In general, women have more severe strokes with worse clinical outcome.”

Furthermore, women were more likely to experience a large vessel occlusion and a penumbral mismatch in the first 24 hours after stroke onset compared with men in previous work evaluating the National Institute of Neurological Disorders and Stroke lesion database.

There can also be differences in how women and men respond to thrombolytic and endovascular treatment, he said. “But the published data have been inconsistent.”

Seeking a more definitive answer, Warach, lead author Adrienne Dula, PhD, and colleagues performed a subanalysis of the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE 3) trial. They wanted to determine if baseline sex differences in core and penumbra imaging measures predict outcomes or differential response to endovascular therapy.

They evaluated 182 adults — 92 women and 90 men. At baseline, DEFUSE 3 participants had a National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater and a modified Rankin Scale (mRS) score of 2 or less.

Overall, women featured a smaller median core volume than men at baseline, 8.0 mL versus 12.6 mL. The difference was not significant (P = .087).

Women also had a smaller median perfusion deficit at baseline, 89 mL, compared with 134 mL among men, defined by a Tmax delay threshold of 6 seconds. This difference was statistically significant (P < .001).

Another favorable finding for women was better collateral function, reflected by a lower median hypoperfusion intensity ratio, 0.31, compared with 0.39 in men (P = .006).

Key Findings

At 24 hours after stroke onset, women had significantly smaller ischemic core growth, a median 22 mL, compared with 42 mL among men (P < .001).

In contrast, reperfusion volumes did not differ significantly by sex (P = .407).

The researchers also assessed outcomes between sexes by whether they received medical or endovascular treatment.

“In the medical treatment arm, outcomes were very similar to the overall sample,” he said, including women having a smaller ischemic core and men experiencing greater lesion growth in 24 hours.

Investigators found no difference between sexes receiving medical treatment regarding mRS scores or functional independence at 90 days. Additionally, outcomes did not differ based on time to randomization.

More striking differences emerged, however, between women and men receiving endovascular therapy plus medical treatment.

“The women had a worse modified Rankin Scale score at 90 days,” Warach said. Median mRS scores at this point were 3.5 among women compared with 2 for men, despite similar NIHSS scores and mRS results at discharge.

Furthermore, fewer women who had endovascular therapy and successful recanalization achieved functional independence at 90 days, 36%, versus 67% of men (P = .016).

Time to randomization and recanalization also differed in this group, which “was about 90 minutes longer in women than men.”

Warach repeatedly emphasized that endovascular therapy was associated with an overall advantage regardless of sex. “Both men and women showed a benefit to thrombectomy versus control, but in the thrombectomy group, nonetheless, women had a worse clinical outcome than men.”

Limitations of the study include its post hoc design, which means there could have been unaccountable factors that could help explain the paradox for women.

Going forward, Warach said, “with support from the Lone Star Stroke Research Consortium, we have started an observational prospective study of baseline multimodal imaging to determine if sex differences in vascular and hemodynamics predict differences in outcome.”

‘Women Should Be Doing Better’

“We’ve known for some time that men and women process stroke differently,” session moderator Justin F. Fraser, MD, director of cerebrovascular surgery in the Department of Neurological Surgery at UK HealthCare at University of Kentucky in Lexington, told Medscape Medical News. “There has been a growing interest in really trying to dig into this.”

For example, although previous studies evaluating uric acid for neuroprotection after stroke appeared unsuccessful, “when you dug into the data, it worked for one sex but not the other,” he added.

More work is needed to evaluate differences in treatment outcomes by sex. “You saw that today with the paradox — by prediction models, women should be doing better but they are doing worse.”

The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS) and support for Dula from the Lone Star Stroke Research Consortium. Warach reported grant support from NINDS StrokeNet and consulting for Genentech. Fraser disclosed no relevant financial relationships.

International Stroke Conference (ISC) 2020. Abstract 56. Presented February 19, 2020.

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