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    Addressing sex and gender differences in stroke risk and management: A scientific statement from the World Stroke Organization
    (SAGE Publications, 2025-10-23)
    Cheryl Carcel
    ;
    Else Charlotte Sandset
    ;
    Mariam Ali
    ;
    Maria Ignacia Allende Echanez
    ;
    Maria Giulia Mosconi
    <jats:p>This World Stroke Organization Scientific Statement highlights how sex and gender differences shape stroke risk, treatment, care, and research. Estrogen confers a relative protection before menopause, with risk increasing thereafter. Beyond shared cardiovascular determinants (hypertension, atrial fibrillation, and diabetes), women face sex-specific risks—hypertensive disorders of pregnancy, menopause, and hormone therapy, with clear implications for stroke prevention and management. Despite comparable efficacy of acute and secondary stroke therapies in women and men, women are less likely to receive timely acute treatment and often experience delays in recognition and access. The statement recommends gender-responsive prevention and care pathways; systematic consideration of pregnancy-related and menopausal factors; and public and professional education to improve stroke symptom recognition and purposeful inclusion of women across the research continuum. By integrating evidence from epidemiology, acute care, and secondary prevention, this statement provides clear and timely guidance for reducing inequities and shaping future research and policy to achieve equitable stroke care globally.</jats:p>
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    Scopus© Citations 93  3
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    Sex differences in treatment, radiological features and outcome after intracerebral haemorrhage: Pooled analysis of Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials 1 and 2
    (2020)
    Else Charlotte Sandset
    ;
    Xia Wang
    ;
    Cheryl Carcel
    ;
    Shoichiro Sato
    ;
    Candice Delcourt
    <jats:sec><jats:title>Introduction</jats:title><jats:p> Reports vary on how sex influences the management and outcome from acute intracerebral haemorrhage. We aimed to quantify sex disparities in clinical characteristics, management, including response to blood pressure lowering treatment, and outcomes in patients with acute intracerebral haemorrhage, through interrogation of two large clinical trial databases. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> Post-hoc pooled analysis of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials 1 and 2, where patients with a hypertensive response (systolic, 150–220 mmHg) after spontaneous intracerebral haemorrhage (&lt;6 h) were randomised to intensive (target &lt;140 mmHg &lt;1 h) or guideline-recommended (&lt;180 mmHg) blood pressure lowering treatment. The interaction of sex on early haematoma growth (24 h), death or major disability (modified Rankin scale scores 3–6 at 90 days), and effect of randomised treatment were determined in multivariable logistic regression models adjusted for baseline confounding variables. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> In 3233 participants, 1191 (37%) were women who were significantly older, had higher baseline National Institutes of Health Stroke Scale scores and smaller haematoma volumes compared to men. Men had higher three-month mortality (odds ratio 1.48, 95% confidence interval 1.10–2.00); however, there was no difference between women and men in the combined endpoint of death or major disability. There were no significant sex differences on mean haematoma growth or effect of randomised blood pressure lowering treatment. </jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p> Men included in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials had more comorbidities, larger baseline haematoma volumes and higher mortality after adjustment for age, as compared with women. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Men included in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials had a greater odds of dying after intracerebral haemorrhage than women, which could not be readily explained by differing casemix or patterns of blood pressure management. </jats:p></jats:sec><jats:sec><jats:title>Clinical trial registration</jats:title><jats:p> The Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials studies are registered with ClinicalTrials.gov (NCT00226096 and NCT00716079). </jats:p></jats:sec>
    Scopus© Citations 15  30
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    Influence of Including Patients with Premorbid Disability in Acute Stroke Trials: The HeadPoST Experience
    (2021)
    Xia Wang
    ;
    Tom J. Moullaali
    ;
    Menglu Ouyang
    ;
    Laurent Billot
    ;
    Else Charlotte Sandset
    <jats:p>&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Patients with premorbid functional impairment are generally excluded from acute stroke trials. We aimed to determine the impact of including such patients in the Head Positioning in acute Stroke Trial (HeadPoST) and early additional impairment on outcomes. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Post hoc analyses of HeadPoST, an international, cluster-randomized crossover trial of lying-flat versus sitting-up head positioning in acute stroke. Associations of early additional impairment, defined as change in modified Rankin scale (mRS) scores from premorbid levels (estimated at baseline) to Day 7 (“early ΔmRS”), and poor outcome (mRS score 3–6) at Day 90 were determined with generalized linear mixed model. Heterogeneity of the trial treatment effect was tested according to premorbid mRS scores 0–1 versus 2–5. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Of 8,285 patients (38.9% female, mean age 68 ± 13 years) with complete data, there were 1,984 (23.9%) with premorbid functional impairment (mRS 2–5). A significant linear association was evident for early ∆mRS and poor outcome (per 1-point increase in ΔmRS, adjusted odds ratio 1.20, 95% confidence interval 1.14–1.27; &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.0001). Patients with greater premorbid functional impairment were less likely to develop additional impairment, but their risk of poor 90-day outcome significantly increased with increasing (worse) premorbid mRS scores (linear trend &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.0001). There was no heterogeneity of the trial treatment effect by level of premorbid function. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Early poststroke functional impairment that exceeded premorbid levels was associated with worse 90-day outcome, and this association increased with greater premorbid functional impairment. Yet, including premorbid impaired patients in the HeadPoST did not materially affect the subsequent treatment effect. &lt;b&gt;&lt;i&gt;Clinical Trial Registration:&lt;/i&gt;&lt;/b&gt; HeadPoST is registered at http://www.ClinicalTrials.gov (NCT02162017). </jats:p>
      1Scopus© Citations 2
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    Degree and Timing of Intensive Blood Pressure Lowering on Hematoma Growth in Intracerebral Hemorrhage Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial-2 Results
    (2016)
    Cheryl Carcel
    ;
    Xia Wang
    ;
    Shoichiro Sato
    ;
    Christian Stapf
    ;
    Else Charlotte Sandset
    <jats:sec> <jats:title>Background and Purpose—</jats:title> <jats:p>Degree and timing of blood pressure (BP) lowering treatment in relation to hematoma growth were investigated in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial-2 (INTERACT2).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods—</jats:title> <jats:p>INTERACT2 was an international clinical trial of intensive (target systolic BP [SBP], &lt;140 mm Hg) versus guideline-recommended (SBP, &lt;180 mm Hg) BP lowering in 2839 patients within 6 hours of spontaneous intracerebral hemorrhage and elevated SBP (150–220 mm Hg), in which 964 had repeat cranial computed tomography at 24 hours. ANCOVA models assessed categories of SBP reduction and time to target SBP on 24-hour hematoma growth.</jats:p> </jats:sec> <jats:sec> <jats:title>Results—</jats:title> <jats:p> Greater SBP reduction was associated with reduced hematoma growth (13.3, 5.0, and 3.0 mL for &lt;10, 10–20, and ≥20 mm Hg, respectively; <jats:italic>P</jats:italic> trend&lt;0.001). In the intensive treatment group (n=491), the least mean hematoma growth was in patients who achieved target SBP &lt;1 hour (2.6 mL) versus to those in target at 1 to 6 (4.7 mL) and &gt;6 hours (5.4 mL). The smallest mean absolute hematoma growth (2.0 mL) was in those achieving target SBP 5 to 8 times versus 3 to 4 (3.1 mL) and 0 to 2 times (5.2 mL). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>Intensive BP lowering with greater SBP reduction, which is achieved quickly and maintained consistently, seems to provide protection against hematoma growth for 24 hours.</jats:p> </jats:sec> <jats:sec> <jats:title>Clinical Trial Registration—</jats:title> <jats:p> URL: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">http://www.clinicaltrials.gov</jats:ext-link> . Unique identifier: NCT00716079. </jats:p> </jats:sec>
    Scopus© Citations 50  1
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    Scopus© Citations 17  1
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    Intracerebral hemorrhage location and outcome among INTERACT2 participants
    (2017)
    Candice Delcourt
    ;
    Shoichiro Sato
    ;
    Shihong Zhang
    ;
    Else Charlotte Sandset
    ;
    Danni Zheng
    <jats:sec><jats:title>Objective:</jats:title><jats:p>To clarify associations between intracerebral hemorrhage (ICH) location and clinical outcomes among participants of the main phase Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2).</jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p>Associations between ICH sites and poor outcomes (death [6] or major disability [3–5] of modified Rankin Scale) and European Quality of Life Scale (EQ-5D) utility scores at 90 days were assessed in logistic regression models.</jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p>Of 2,066 patients included in the analyses, associations were identified between ICH sites and poor outcomes: involvement of posterior limb of internal capsule increased risks of death or major disability (odds ratio [OR] 2.10) and disability (OR 1.81); thalamic involvement increased risks of death or major disability (OR 2.24) and death (OR 1.97). Involvement of the posterior limb of the internal capsule, thalamus, and infratentorial sites were each associated with poor EQ-5D utility score (≤0.7 [median]; OR 1.87, 2.14, and 2.81, respectively). Posterior limb of internal capsule involvement was strongly associated with low scores across all health-related quality of life domains. ICH encompassing the thalamus and posterior limb of internal capsule were associated with death or major disability, major disability, and poor EQ-5D utility score (OR 1.72, 2.26, and 1.71, respectively).</jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p>Poor clinical outcomes are related to ICH affecting the posterior limb of internal capsule, thalamus, and infratentorial sites. The highest association with death or major disability and poor EQ-5D utility score was seen in ICH encompassing the thalamus and posterior limb of internal capsule.</jats:p></jats:sec><jats:sec><jats:title>ClinicalTrials.gov registration:</jats:title><jats:p>NCT00716079.</jats:p></jats:sec>
    Scopus© Citations 121  1
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    Sex differences in treatment and outcome after stroke Pooled analysis including 19,000 participants
    (2019)
    Cheryl Carcel
    ;
    Xia Wang
    ;
    Else Charlotte Sandset
    ;
    Candice Delcourt
    ;
    Hisatomi Arima
    <jats:sec><jats:title>Objective</jats:title><jats:p>To explore the sex differences in outcomes and management after stroke using a large sample with high-quality international trial data.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Individual participant data were obtained from 5 acute stroke randomized controlled trials. Data were obtained on demographics, medication use, in-hospital treatment, and functional outcome. Study-specific crude and adjusted models were used to estimate sex differences in outcomes and management, and then pooled using random-effects meta-analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>There were 19,652 participants, of whom 7,721 (40%) were women. After multivariable adjustments, women with ischemic stroke had higher survival at 3–6 months (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.70–0.97), higher likelihood of disability (OR 1.20, 95% CI 1.06–1.36), and worse quality of life (weighted mean difference −0.07, 95% CI −0.09 to 0.04). For management, women were more likely to be admitted to an acute stroke unit (OR 1.17, 95% CI 1.01–1.34), but less likely to be intubated (OR 0.58, 95% CI 0.36–0.93), treated for fever (OR 0.82, 95% CI 0.70–0.95), or admitted to an intensive care unit (OR 0.83, 95% CI 0.74–0.93). For preadmission medications, women had higher odds of being prescribed antihypertensive agents (OR 1.22, 95% CI 1.13–1.31) and lower odds of being prescribed antiplatelets (OR 0.86, 95% CI 0.79–0.93), glucose-lowering agents (OR 0.86, 95% CI 0.78–0.94), or lipid-lowering agents (OR 0.85, 95% CI 0.77–0.94).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>This analysis suggests that women who had ischemic stroke had better survival but were also more disabled and had poorer quality of life. Variations in hospital and out-of-hospital management may partly explain the disparities.</jats:p></jats:sec>
      1Scopus© Citations 115  2