On the Basis of Sex.

See related articles, p 2299, 2413, 2420 Sex differences in ischemic stroke outcome have been reported in many published studies, and 3 recent articles in Stroke highlight these differences. It is clear that women have poorer outcomes than men, but increasing recognition of important confounders, most notably higher rates of prestroke disability experienced by women, has led to a more nuanced understanding of what accounts for these poorer outcomes. In large epidemiological data sets, on an average women are 5 years older than men when they experience their first stroke. However, when age is controlled in multivariable models, women still fare worse. But is controlling for age enough? New studies reveal that other factors like prestroke functional status and poststroke depression are key contributors to the sex differences seen in stroke outcome. The poorer baseline function in women may also have major implications for women’s access to acute interventional treatments, as they may be selected out of clinical trials or therapies based on their higher premorbid modified Rankin Scale (mRS). This is an especially important factor to consider as the article by Sheth et al in this issue found that women are as likely, and perhaps more likely, to benefit from endovascular treatment. The first study by Phan et al investigated sex differences in health-related quality of life in stroke survivors in the INSTRUCT (International Stroke Outcomes Study). INSTRUCT was an international collaboration that had individual participant data from 13 studies from patients with first ever stroke. The authors analyzed data from 4 studies that obtained health-related quality of life at 1 and 5 years poststroke. As has been reported by others, the authors found that women have a poorer health-related quality of life at both 1 and 5 years after their first stroke (1 year median difference, −0.147; 5 year median difference, −0.090) as compared to men. However, when age, stroke severity, prestroke dependency, and poststroke depression were included in the quantile regression model, the sex difference in outcome was no longer significant (1 year median difference, −0.067, 5 year median difference, −0.085). This is consistent with previous work reported for stroke mortality in 2017, also using the INSTRUCT cohort. Using Poisson modeling, it was found that women had a higher mortality rate ratio (MRR) at 1 (MRR, 1.35; 35% higher) and 5 (MRR, 1.24; 24% higher) years poststroke. When controlled for age, prestroke functional status, stroke severity, and history of atrial fibrillation, the sex differences reversed at 1 (MRR, 0.81) and 5 years (MRR, 0.76). This current article by Phan et al confirms that sex differences in stroke outcome follow the same pattern as those seen in mortality and stroke severity. Perhaps, most importantly, this study clearly highlights the importance of capturing an assessment of prestroke function in large epidemiological studies. This has been seen in other cohorts, including those enrolled in the Oxford Vascular Study. Poorer outcomes seen after stroke or transient ischemic attack in women at 1 month, 6 months, 1 year, and 5 years were no longer significant after controlling for premorbid mRS. One important limitation of the current article by Phan et al was the high number of patients lost to follow-up in the INSTRUCT cohort (72.5% in the Perth study and 61.6% in the Auckland study). Death or discharge to nursing facilities, which may be more common in older women, remain important outcome measures, and loss of these data points may lead to erroneous conclusions. Obtaining follow-up data, although costly, should be a priority in these large epidemiological studies to more accurately determine outcomes for both men and women. It is clear that strategies to improve overall functional status would greatly benefit older stroke survivors, many of which are women. However, reversing the detrimental effects of aging is a difficult task, and new approaches are clearly needed. The second published article by Sheth et al examined the effect of sex on outcomes after endovascular therapy (EVT) for acute ischemic stroke. Patients from 3 trials, SWIFT (Solitaire FR With the Intention for Thrombectomy), STAR (Solitaire FR Thrombectomy for Acute Revascularization), and SWIFTPRIME (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment) were analyzed to determine sex differences in disability adjusted life years after EVT. Consistent with the study by Phan et al, there was no sex difference in functional outcome after 90 days, despite the fact women were older and had higher rates of atrial fibrillation. However, when adjusted for factors including age, premorbid mRS, and stroke severity, women had higher disability adjusted life years after EVT as compared to men (10.6 versus 8.5 years). This suggests that women are as likely and perhaps even more likely to benefit from endovascular intervention. The third article by Chalos et al presented pooled results from 7 trials within the HERMES collaboration to assess the The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston. Guest Editor for this article was Natalia S. Rost, MD, MPH. Correspondence to Louise D. McCullough, MD, PhD, Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St, MSB 7.005E, Houston, TX 77030. Email Louise.D.McCullough@uth.tmc.edu On the Basis of Sex Outcomes After Ischemic Stroke