Issue: February 2021
Disclosures: One author reports he received speaker honoraria from Bristol Myers Squibb and Medtronic and served on a scientific advisory board for Medtronic. The other authors report no relevant financial disclosures.
January 26, 2021
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In acute ischemic stroke, women present with greater severity than men

Issue: February 2021
Disclosures: One author reports he received speaker honoraria from Bristol Myers Squibb and Medtronic and served on a scientific advisory board for Medtronic. The other authors report no relevant financial disclosures.
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Women admitted for acute ischemic stroke more often presented with a higher degree of disability and were more likely to undergo intra-arterial thrombolysis compared with men, according to research published in Stroke.

“In the present study, sex differences were substantially altered by the inclusion of covariates in all but two outcomes: Women were more likely to receive intra-arterial therapy and to have a higher stroke severity upon admission independent of the considered covariates,” Anna K. Bonkhoff, MD, research fellow in neurology at the J. Philip Kistler Stroke Research Center at Massachusetts General Hospital, and colleagues wrote. “In all other cases, covariates could either fully explain the difference between men and women or even change the direction of the sex differences (in-hospital mortality and favorable functional outcome). This marked covariate-dependence of conclusions highlights the importance of precise reporting and interpretation as well as necessity of ensuring accurate comparisons.”

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For the analysis of the Stroke Registry of Northwestern Germany, researchers identified sex differences in acute ischemic stroke by looking at admission-stroke severity and disability, acute recanalization treatment and early stroke outcomes. This study included 761,106 patients (mean age, 72 years; 48% women) admitted with acute ischemic stroke from 2000 to 2018.

Sex differences at presentation

Overall, women were more likely to be admitted with an elevated degree of disability (Rankin Scale score of > 2) in 2000 through 2018, independent of covariates.

Age did not explain the increased level of disability upon admission among women. Researchers observed substantial sex differences in disability in base models (OR in 2000 = 1.19; 95% CI, 1.16-1.21; OR in 2010 = 1.17; 95% CI, 1.15-1.18).

The sex differences were partially explained by covariates such as the time between symptom onset and admission, premorbid functional status and stroke etiology.

In addition, women presented with more severe stroke symptoms than men after accounting for covariates (OR in 2000 = 1.1; 95% CI, 1.07-1.13; OR in 2010 = 1.09; 95% CI, 1.07-1.1).

Sex differences in stroke treatment

After adjustment for age and the year of admission, women were less likely to receive IV thrombolysis (IVT) from 2000 to 2009 (OR = 0.96; 95% CI, 0.92-0.99), but more likely to receive IVT from 2010 to 2018 (OR = 1.04; 95% CI, 1.03-1.06).

After adjustment for degree of disability upon admission, women were less likely to receive IVT during both study periods (OR in 2000 = 0.86; 95% CI, 0.83-0.9; OR in 2010 = 0.95; 95% CI, 0.94-0.97).

After full adjustment, researchers found no sex differences for treatment with IVT (OR in 2000 = 0.99; 95% CI, 0.94-1.03; OR in 2010 = 1; 95% CI, 0.98-1.02).

“We found that sex differences in the administration of IVT depended on the inclusion of covariates and the period of data acquisition. When considering unadjusted or only age-adjusted analyses, women were less likely to receive IVT than men in the period from 2000 to 2009,” the researchers wrote. “This comparatively lower chance of IVT in women disappeared for data originating from the years 2010 to 2018.”

In the fully adjusted model, women were more likely to undergo intra-arterial therapy for stroke compared with men (OR = 1.12; 95% CI, 1.08-1.15).

“Irrespective of whether crude or adjusted effects were considered, women were significantly more likely to be treated with intra-arterial thrombolysis or thrombectomy,” the researchers wrote. “While previous studies did not have access to further clinical variables, we observed a decrease in the extent of sex divergences when introducing further information, eg, initial symptom load or stroke etiology. However, even the entirety of all considered covariates could still not fully explain why female stroke patients were more likely to undergo acute intra-arterial therapy.”

Sex differences in early outcomes

Initially, women experienced greater risk for in-hospital mortality compared with men (OR in 2000 = 1.11; 95% CI, 1.07-1.17; OR in 2010 = 1.15; 95% CI, 1.12-1.18); however, the association flipped after adjustment for degree of disability upon admission and other covariates (OR in 2000 = 0.92; 95% CI, 0.86-0.97; OR in 2010 = 0.91; 95% CI, 0.88-0.93).

In base models, men experienced more favorable outcomes after hospitalization for acute ischemic stroke compared with women (OR in 2003 = 0.83; 95% CI, 0.81-0.85; OR in 2010 = 0.84; 95% CI, 0.83-0.85). However, after adjusting for age, year of admission, degree of disability upon admission, time from symptom onset to admission, level of necessary care before admission, comorbidities and stroke etiology, women were more likely to have favorable outcomes after stroke compared with men for both study periods (OR in 2003 = 1.08; 95% CI, 1.04-1.12; OR in 2010 = 1.05; 95% CI, 1.04-1.07).

“We found that women had significantly more severe strokes upon admission and nonetheless significantly lower in-hospital mortality and more favorable functional outcomes at discharge compared to men, when all covariates were taken into account,” the researchers wrote. “This finding suggested that factors other than the ones considered here contributed to the higher stroke severity. However, in the course of the hospital treatment, women with acute ischemic stroke had a more successful in-hospital recovery, since they showed a lower chance of in-hospital mortality and unfavorable functional outcome at discharge.”

Excluding patients transferred between acute care hospitals on the day of admission did not change the results.

“To fully embrace the implications of sex in acute ischemic stroke, it is of importance to not only recognize sex differences, but also to strive to understand their origin in sociodemographic and clinical characteristics,” the researchers wrote. “By these means, it might be possible to determine how potential sex differences may be counteracted. This could lead to clinically actionable, novel approaches. In the long term, these insights could motivate the extension of previously composed sex-specific guidelines on stroke prevention to sex-specific guidelines on acute and chronic stroke management.”