LOS ANGELES – Although women seem to have more favorable vascular and hemodynamic measures after an ischemic stroke than men, on the whole, they present worse functional results, they demonstrate new evidence. The results suggest that other factors could drive 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 International Stroke Conference (ISC) 2020.
“This was true even among those who have achieved satisfactory recanalization,” he added.
The findings were also published online in the February 2020 issue of Stroke.
Blow Blow Differently
Sexual differences in ischemic stroke are well known, said Warach, a professor of neurology at the University of Texas at Austin Dell Medical School. “In general, women have more severe strokes with worse clinical outcomes.”
In addition, women were more likely to experience a large vessel occlusion and penumbral discrepancy in the first 24 hours after stroke onset than men in previous evaluation work by the National Institute for Neurological Disorders and the database of stroke injuries.
There may also be differences in how women and men respond to thrombolytic and endovascular treatment, he said. “But the published data have been inconsistent.”
In search of a more definitive answer, Warach, lead author Adrienne Dula, PhD and colleagues performed a sub-analysis of the endovascular therapy study after assessing ischemic stroke imaging (DEFUSE 3). They wanted to determine whether baseline sexual differences in core and penumbra imaging measures predict outcome or differential response to endovascular therapy.
They rated 182 adults – 92 women and 90 men. At baseline, participants in DEFUSE 3 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 had a lower median mean volume than men at baseline, 8.0 ml versus 12.6 ml. The difference was not significant (P = .087).
The women also had a median perfusion deficit lower than baseline, 89 ml, compared to 134 ml among men, defined by a delay threshold Tmax of 6 seconds. This difference was statistically significant (P <.001).
Another favorable outcome for women was better collateral function, reflected by a lower median hypoperfusion intensity ratio, 0.31, compared to 0.39 in men (P = .006).
At 24 hours from the onset of stroke, women had significantly lower ischemic nucleus growth, a median of 22 ml, compared to 42 ml in men (P <.001).
In contrast, reperfusion volumes did not differ significantly by gender (P = .407).
The researchers also assessed the results between the sexes if they received medical or endovascular treatment.
“In the medical treatment arm, the results were very similar to the overall sample,” he said, including women with a smaller ischemic core and men who experience greater injury growth in 24 hours.
Investigators found no difference between sexes undergoing medical treatment regarding MRS scores or 90-day functional independence. Furthermore, the results did not differ based on the randomization time.
More noticeable differences emerged, however, between women and men undergoing endovascular therapy plus medical care.
“The women had a modified Rankin Scale score worse at 90 days,” Warach said. The mean mRS scores at this point were 3.5 in women compared to 2 for men, despite similar NIHSS scores and mRS results at discharge.
In addition, fewer women undergoing endovascular therapy and successful recanalization achieved functional independence at 90 days, 36%, compared to 67% of men (P = .016).
The randomization and recanalization time also differed in this group, which “was about 90 minutes longer in women than men.”
Warach has repeatedly stressed that endovascular therapy was associated with an overall benefit regardless of gender. “Both men and women showed a benefit for thrombectomy over control, but in the thrombectomy group, however, women had a worse clinical outcome than men.”
The limitations of the study include its post hoc design, which means that there may have been unexplained factors that could help explain the paradox for women.
Going forward, Warach said, “with the support of the lone star stroke research consortium, we initiated a prospective observational study of basic multimodal imaging to determine whether sexual differences in vascularization and hemodynamics predict differences in outcomes.”
“Women should do better”
“We have known for some time that men and women treat stroke differently,” session moderator Justin F. Fraser, MD, director of cerebrovascular surgery in the Department of Neurological Surgery at the UK’s HealthCare at the University from Kentucky to Lexington Medscape medical news. “There has been growing interest in really trying to dig into this.”
For example, although previous studies evaluating uric acid for neuroprotection after stroke appeared to be unsuccessful, “when you delved into the data, it worked for one sex but not the other,” he added.
More work is needed to assess the differences in treatment outcomes by gender. “You have seen that today with the paradox – according to prediction models, women should do better but they are getting 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 has reported support from NINDS StrokeNet and advice for Genentech. Fraser did not disclose relevant financial reports.
International Stroke Conference (ISC) 2020. Abstract 56. Presented February 19, 2020.
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