Sex-based differences in outcomes following endovascular therapy for anterior circulation large vessel occlusion: a pooled analysis of DEVT, RESCUE BT, and MARVEL trials

Abstract

Background:

This study sought to characterize sex-specific treatment effects by comparing clinical outcomes between men and women undergoing EVT.

Methods:

Analyses were based on the DEVT, RESCUE BT, and MARVEL databases. Men and women were matched using propensity score matching (PSM). The primary outcome was defined as the 90-day ordinal modified Rankin Scale score (mRS) distribution. Secondary outcomes included the favorite outcome (mRS 0 to 3), functional independence (mRS 0 to 2), and excellent outcome (mRS 0 to 1). Safety outcomes were symptomatic intracranial hemorrhage (sICH) and mortality.

Results:

Of 2,862 patients, 1,221 (42.7%) were women and 1,641 (57.3%) were men. After adjusting for covariates, there were no sex differences in 90-day ordinal mRS distribution (median [interquartile range], 3 [1–6] versus 3 [1–5], common odds ratio [OR], 1.02 [0.89–1.18], p = 0.741). The secondary outcomes demonstrated consistency with the primary findings, and the safety outcomes remained stable across men and women. After 1:1 PSM, the results remained consistent with the adjusted outcomes described above.

Conclusion:

This pooled analysis demonstrated that no statistically significant differences were observed between men and women in clinical or safety outcomes following EVT for anterior circulation LVO. Furthermore, there was no evidence of interaction between sex and predefined subgroups in terms of treatment effect modification for EVT outcomes.

Introduction

Ischemic stroke caused by large vessel occlusion (LVO) in the anterior circulation is a leading cause of disability and mortality worldwide (1). Over the past decade, endovascular treatment (EVT) has become the optimal therapy for eligible patients, as multiple landmark randomized controlled trials have demonstrated superior recanalization rates and functional independence compared to medical therapy alone (2–5). Despite significant technical advancements in EVT, clinical outcomes continue to demonstrate substantial heterogeneity across the patient population. This variability has motivated extensive research into potential determinants of treatment efficacy. Notably, sex differences have garnered increasing attention (6, 7).

Existing research presents conflicting evidence regarding sex-based disparities in EVT outcomes. While multiple studies suggest women experience poorer functional independence and higher post-procedural mortality rates, which may be attributable to several sex-specific factors (8–10). Epidemiological studies highlight that women tend to present with more severe strokes at older ages (11, 12) and have higher pre-stroke disability rates (6). Moreover, sexually biological differences appear to play a significant role, including sexually dimorphic cerebrovascular anatomy and hormone-mediated vascular responses that may influence treatment efficacy (13, 14). Furthermore, sociodemographic disparities in access to acute stroke care and post-stroke rehabilitation may explain significant variations in patient outcomes (15, 16). However, this view is not universal, as other studies have reported comparable outcomes between the sexes following EVT (7, 17, 18). Importantly, overreliance on small-sample studies, which are prone to selection bias and inadequate confounder adjustment, may lead to overestimation or misinterpretation of sex differences in EVT outcomes.

Using the data from the DEVT, RESCUE BT, and MARVEL trials (19–21). This study sought to investigate sex-based differences in outcomes by comparing clinical outcomes between men and women undergoing EVT.

Methods

Study population and design

The AIS patients who underwent EVT treatment for anterior circulation LVO were selected from three randomized controlled trials, including the Direct Endovascular Thrombectomy versus Combined IVT and Endovascular Thrombectomy for Patients with Acute Large Vessel Occlusion in the Anterior Circulation (DEVT trial) (19), the Endovascular Treatment With versus Without Tirofiban for Patients with Large Vessel Occlusion Stroke (RESCUE BT trial) (20), and the Methylprednisolone as Adjunctive to Endovascular Treatment for Acute Large Vessel Occlusion (MARVEL trial) (21) (Supplementary Figure 1). The three trials followed the ethical principles of the Helsinki Declaration and were approved by the ethics committees of the Xinqiao Hospital, Army Medical University, and all participating centers. Written informed consent was taken from all patients or their legal representatives before they were enrolled in these trials. The inclusion criteria, data collection, methods, and radiological assessment of the three trials were reported previously.

Data collection

The following details of the patients were extracted from the combined database: sex, age, and stroke risk factors, including coronary heart disease, atrial fibrillation, valvular heart disease, hypertension, diabetes mellitus, hyperlipidemia, transient ischemic attack, cerebral infarction, intracranial hemorrhage, and smoking history. Furthermore, the cerebral artery occlusion site, baseline glucose, and stroke etiology by the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification (22), baseline National Institutes of Health Stroke Scale (NIHSS) score (23), systolic blood pressure upon admission, the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral vessel grading system (24), the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) (25), time from stroke onset to puncture (OTP), and onset to recanalization (OTR) were all included. Two researchers independently collected the data, and any discrepancies were resolved through consensus. If agreement could not be reached, a third researcher was consulted. The quality of reperfusion was evaluated by the expanded Thrombolysis in Cerebral Infarction (eTICI) grade on the final angiogram (26).

Outcome measures

The primary outcome was defined as the 90-day ordinal modified Rankin Scale score (mRS) distribution. The mRS score ranges from 0 (indicating no residual symptoms) to 6 (indicating death) (27). Secondary outcomes included the favorite outcome (mRS 0 to 3), functional independence (mRS 0 to 2), and excellent outcome (mRS 0 to 1). The safety outcomes were symptomatic intracranial hemorrhage (sICH), assessed according to the Heidelberg bleeding classification (28), mortality within 90 days, and any intracranial hemorrhage.

Statistical analysis

The variable’s statistics were computed based on the data type. The continuous variables were presented as a median and interquartile range (IQR). Categorical variables were reported as numbers and percentages. The differences between the men and women groups were compared using the Mann–Whitney U-test for continuous and ordinal variables and the Pearson’s χ2 test or Fisher’s exact test for categorical variables.

Furthermore, for the analysis of binary outcomes, binary logistic regression was used, such as mRS 0 to 3, mRS 0 to 2, mRS 0 to 1, sICH, mortality within 90 days, and any intracranial hemorrhage. For ordinal outcomes (e.g., modified Rankin Scale scores), ordinal logistic regression was performed, and results are reported as common odds ratios (common ORs). For binary outcomes, binary logistic regression was used, and results are reported as odds ratios (ORs). Based on the prior literature and the unique characteristics of the present dataset, the following covariates were adjusted for in the analysis: age, atrial fibrillation, hypertension, diabetes, baseline ASPECTS, baseline NIHSS, occlusion site, stroke etiology, anesthesia, and intravenous thrombolysis.

To reduce bias between the women’s and men’s groups, we performed a propensity score matching (PSM) analysis. Using the nearest-neighbor matching algorithm, the covariates were balanced 1:1 with a caliper width of 0.1. PSM used the same adjustment factors as logistic regression. In the matched population, sex-based outcome differences were quantified using binary and ordinal logistic regression models, with results reported as ORs and common ORs.

Subgroup analyses was performed by testing the interaction effect using the binary logistic regression model to investigate sex modification on the primary outcome in the following subgroups from the post-matched population: age (age <75 years versus age ≥75 years), baseline NIHSS (<15 versus ≥15), baseline ASPECTS (<6 versus ≥6), pretreatment with intravenous thrombolysis (yes versus no), stroke etiology (large artery atherosclerosis versus cardioembolism versus other or unknown etiology), usage of tirofiban (yes versus no), and OTP (>340 min versus ≤340 min).

For statistical assessment, IBM SPSS Statistics 26 (SPSS Inc.) and R version 4.4.2 (R Foundation for Statistical Computing, Vienna, Austria) were used. All tests were two-sided and considered statistically significant at a p-value of <0.05. A simple imputation method was used for imputing missing values (Supplementary Method 2).

Results

Baseline characteristics

Of the patients, 2,862 were included in the analysis. There were 1,641 (57.3%) men and 1,221 (42.7%) women. Women were older (median 72 [IQR, 64–78] versus 65[IQR, 56–73], p < 0.001) and had a lower rate of smoking (1.1% versus 45.3%, p < 0.001). However, women had a higher prevalence of cardiac heart disease (23.8% versus 14.1%, p < 0.001), atrial fibrillation (52.4% versus 30.2%, p < 0.001), and diabetes (21.9% versus 18.5%, p < 0.001). Women had higher stroke severity by median (IQR) NIHSS score at presentation (18[16–21] versus 17[14–20], p < 0.001), higher baseline glucose (7.10[6.30–8.90] versus 7.00[5.90–8.10], p < 0.001), shorter median (IQR) onset to puncture time (316[217–540] versus 366[235–619], p < 0.001), and shorter median (IQR) onset to recanalization time (400[290–615] versus 454[315–715], p < 0.001). The prevalence of stroke subtype according to TOAST criteria was significantly different between groups (p < 0.001). LAA was higher in men (49.5% versus 26.5%), while cardioembolism was higher in women (62.0% versus 36.3%). There were significant differences in the first choice of EVT (p < 0.001). The use of stent thrombectomy was lower in women (22.4% versus 24.0%). Aspiration was higher in women (46.8% versus 41.0%). Solitaire stent with intracranial support catheter for mechanical thrombectomy (SWIM) was higher in men (20.6% versus 22.9%). Other detailed patient characteristics are presented in Table 1. A total of 1,029 men were successfully matched with 1,029 women presenting with large vessel occlusion. After 1:1 PSM, baseline characteristics were well-balanced between the two groups, except for a history of coronary heart disease and smoking status (Table 1; Supplementary Method 1).

Clinical outcomes

Table 2 provides primary, secondary, and safety outcome comparisons between men and women. Before adjusting for the confounders, we found that men had a shift to better outcomes (3[1–6] versus 3[1–5], common OR, 1.37[1.21–1.57], p < 0.001; Figure 1A), higher odds of favorable outcome (54.6% versus 63.1%, OR 1.42[1.22–1.65], p < 0.001), higher odds of functional independence (40.1% versus 48.1%, OR, 1.38[1.19–1.60], p < 0.001), higher odds of excellent outcome (25.3% versus 32.2%, OR, 1.40[1.19–1.66], p < 0.001), and lower odds of mortality (25.1% versus 20.6%, OR, 0.78[0.65–0.93], p = 0.005) than women.

Figure 1

After adjusting for confounders, all outcomes were similar between men and women. After 1:1 PSM, there was no difference in primary, secondary, and safety outcomes. In the primary outcomes, the shift to mRS between women and men showed no difference (3[1–5] versus 3[1–5], common OR, 1.03[0.88–1.20]; p = 0.712; Figure 1B). In the secondary outcomes, mRS 0 to 3 was observed in 579 of 1,029 (56.3%) women and 587 of 1,029 (57.0%) men (OR, 0.98[0.81–1.19], p = 0.874), mRS 0 to 2 was observed in 420 (40.8%) of women and 464 (45.1%) of men (OR,1.24[0.99–1.55], p = 0.079), and mRS 0 to 1 was observed in 272 (26.4%) of women and 302 (29.3%) of men (OR,1.15[0.93–1.51], p = 0.195). In the safety outcomes, sICH was observed in 90 (8.7%) of women and 108 (10.5%) of men (OR,1.24[0.92–1.67], p = 0.162), mortality was observed in 251 (24.4%) of women and 256 (24.9%) of men (OR,1.07[0.86–1.32], p = 0.542), and any intracranial hemorrhage was observed in 360 (35.0%) of women and 371 (36.1%) of men (OR,1.05[0.88–1.27], p = 0.576).

Subgroup analysis

The shift to mRS at 90 days remained consistent across the pre-defined subgroups, including age (age <75 years versus age ≥75 years), baseline ASPECTS (<6 versus ≥6), pretreatment with intravenous thrombolysis (yes versus no), stroke etiology (large artery atherosclerosis versus cardio embolism versus other or unknown etiology), usage of tirofiban (yes versus no), and OTP (>340 min versus ≤340 min) (Figure 2). There was no interaction between sex and pre-defined subgroup in terms of the treatment effect modification in EVT outcomes.

Figure 2

Marginal effect and outcomes

We analyzed the association of age, baseline NIHSS score, and baseline ASPECTS with clinical outcomes (defined as an mRS score of 0 to 2 and mortality) among patients stratified by sex. The results showed that for both men and women, the predicted probability of achieving an mRS score of 0–2 gradually decreased with increasing age and baseline NIHSS score but increased with higher baseline ASPECTS. In contrast, the predicted probability of mortality showed the opposite trend. No interaction effects were observed among the different subgroups (Figure 3).

Figure 3

Discussion

Based on the DEVT, RESCUE BT, and MARVEL databases, a large sample size of 2,862 patients was selected, and baseline and outcome data were analyzed. Our findings demonstrated that there were no significant differences in clinical or safety outcomes between men and women following EVT for anterior circulation LVO. Additionally, no interaction was observed between sex and predefined subgroups regarding the treatment effect of modification in EVT outcomes.

This study revealed significant gender disparities in baseline demographic characteristics and clinical presentations. Notably, fewer women underwent EVT compared to men. Previous studies have suggested that the reduced utilization of EVT in women compared to men may be attributable to their less favorable baseline characteristics, including a higher prevalence of living alone, advanced age, and greater pre-stroke disability (29). In our study, we found that women patients were not only significantly older than men patients but also exhibited markedly higher prevalence rates of cardiac heart disease, atrial fibrillation, and valvular pathologies. This distinct clinical profile was associated with a higher incidence of cardioembolic events in women, which may potentially explain the observed shorter endovascular treatment procedure times compared to men, consistent with findings from recent studies (7, 30). In contrast, men showed significantly higher rates of smoking and tandem lesions, with large artery atherosclerosis being the predominant etiology. The distinct vascular risk factor profiles observed between groups in the pre-matched cohort may account for the differential pathophysiology of large vessel occlusion.

Other than baseline demographic characteristics and clinical presentations, sex-specific factors may affect the differences in post-EVT outcomes. A questionnaire study revealed that women who arrived at the hospital more than 3 h after symptom onset were significantly more likely to report reluctance to trouble others and adopt a “wait-and-see” approach for potential symptom resolution and were more likely to rest, take medication to treat symptoms, hide symptoms from others, and continue with usual activities (31). Additionally, women are at higher risk for poststroke depression and have reduced mobility compared with men, which may significantly impact their post-intervention rehabilitation outcomes (32). Moreover, based on the cardiovascular protective effects of endogenous estrogen, several studies have investigated the relationship between female reproductive lifespan (defined as menopause age minus menarche age) and ischemic stroke risk (33, 34). Research consistently shows that women with shorter reproductive lifespans face a significantly increased risk of developing ischemic stroke (35, 36).

Consistent with prior evidence, our analysis revealed that there was no interaction between sex and pre-defined subgroup in terms of the treatment effect modification in EVT outcomes (37). While a recent late-window EVT study similarly found no sex-based differences in functional outcomes, they reported age-dependent risks in male patients for mortality (P_interaction = 0.003) and symptomatic intracranial hemorrhage (P_interaction = 0.017), an effect not observed in our cohort (mortality: p = 0.534; sICH: p = 0.685; Supplementary Figures 2, 3). The authors attributed these findings to biological, genetic, and socio-economic factors (38). Another study showed that in patients with an NIHSS score of <15, women tended to have a better outcome than men, whereas there was no gender effect in those with an NIHSS score of ≥15. Regrettably, the research did not pursue mechanistic studies to explain these sex-specific outcome patterns (30).

However, with improved health care coverage, optimized treatment protocols, significantly enhanced public stroke awareness, and strong governmental policy support, women have demonstrated greater improvements in outcomes compared to men over the past decade (39). Moreover, the absence of sex-based disparities in functional outcomes may be attributed to improved stroke awareness among younger women, leading to earlier diagnosis, more timely treatment, enhanced rehabilitation access, and ultimately superior clinical outcomes (34). Additionally, women exhibit distinct cerebrovascular anatomical characteristics, including smaller arterial diameters, higher tortuosity indices, and more robust collateral circulation (40). They may benefit from the use of less traumatic EVT devices that reduce the risk of vessel perforation, which may not be as deleterious as in men, given their better collateral circulation (9).

Limitation

There are some limitations to our study. First, as this is a pooled analysis of three randomized controlled trials, all participants were selected under strict trial criteria. This may result in differences between our study sample and the broader real-world EVT population in terms of age, comorbidity burden, and workflow times. Second, only data from patients with an anterior circulation LVO who received EVT were evaluated, so we cannot determine whether similar sex differences exist among posterior circulation LVO stroke patients. Third, our study focused primarily on evaluating outcomes within the 90-day post-treatment window, a time point widely recognized as clinically meaningful for assessing recovery and functional outcomes in ischemic stroke. The existence of sex-based differences in long-term functional outcomes following EVT remains an area of active investigation, with current findings presenting inconsistencies. Therefore, caution is warranted when generalizing the conclusions of this study to all anterior circulation large-vessel occlusion patients in routine clinical practice. Future studies are needed to validate these findings in real-world cohorts.

Conclusion

This pooled analysis demonstrated that no statistically significant differences were observed between men and women in clinical or safety outcomes, following EVT for anterior circulation LVO. Furthermore, there was no evidence of an interaction between sex and predefined subgroups in terms of treatment effect modification for EVT outcomes.

References

• 1.

  GBD 2021 Stroke Risk Factor Collaborators . Global, regional, and national burden of stroke and its risk factors, 1990-2021: a systematic analysis for the global burden of disease study 2021. Lancet Neurol. (2024) 23:973–1003. doi: 10.1016/s1474-4422(24)00369-7

  • CrossRef
  • Google Scholar

• 2.

  Goyal M Demchuk AM Menon BK Eesa M Rempel JL Thornton J et al . Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. (2015) 372:1019–30. doi: 10.1056/NEJMoa1414905,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 3.

  Campbell BC Mitchell PJ Kleinig TJ Dewey HM Churilov L Yassi N et al . Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. (2015) 372:1009–18. doi: 10.1056/NEJMoa1414792,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 4.

  Saver JL Goyal M Bonafe A Diener HC Levy EI Pereira VM et al . Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. (2015) 372:2285–95. doi: 10.1056/NEJMoa1415061,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 5.

  Goyal M Menon BK van Zwam WH Dippel DW Mitchell PJ Demchuk AM et al . Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. (2016) 387:1723–31. doi: 10.1016/s0140-6736(16)00163-x,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 6.

  Wang M Wang CJ Gu HQ Meng X Jiang Y Yang X et al . Sex differences in short-term and Long-term outcomes among patients with acute ischemic stroke in China. Stroke. (2022) 53:2268–75. doi: 10.1161/strokeaha.121.037121,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 7.

  Regenhardt RW Turner AC Hirsch JA Young MJ Alotaibi NM Stapleton CJ et al . Sex-specific differences in presentations and determinants of outcomes after endovascular thrombectomy for large vessel occlusion stroke. J Neurol. (2022) 269:307–15. doi: 10.1007/s00415-021-10628-0,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 8.

  Fifi JT Nguyen TN Song S Sharrief A Pujara DK Shaker F et al . Sex differences in endovascular thrombectomy outcomes in large vessel occlusion: a propensity-matched analysis from the SELECT study. J Neurointerv Surg. (2023) 15:105–12. doi: 10.1136/neurintsurg-2021-018348,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 9.

  Ospel JM Schaafsma JD Leslie-Mazwi TM Amin-Hanjani S Asdaghi N Gordon-Perue GL et al . Toward a better understanding of sex- and gender-related differences in endovascular stroke treatment: a scientific statement from the American Heart Association/American Stroke Association. Stroke. (2022) 53:e396–406. doi: 10.1161/str.0000000000000411,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 10.

  Ryu WS Chung J Schellingerhout D Jeong SW Kim HR Park JE et al . Biological mechanism of sex difference in stroke manifestation and outcomes. Neurology. (2023) 100:e2490–503. doi: 10.1212/wnl.0000000000207346,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 11.

  Sheth SA Lee S Warach SJ Gralla J Jahan R Goyal M et al . Sex differences in outcome after endovascular stroke therapy for acute ischemic stroke. Stroke. (2019) 50:2420–7. doi: 10.1161/strokeaha.118.023867,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 12.

  Lorenzano S Ahmed N Falcou A Mikulik R Tatlisumak T Roffe C et al . Does sex influence the response to intravenous thrombolysis in ischemic stroke?: answers from safe implementation of treatments in stroke-international stroke thrombolysis register. Stroke. (2013) 44:3401–6. doi: 10.1161/strokeaha.113.002908,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 13.

  Davison MA Ouyang B Keppetipola KM Chen M . Arterial diameter and the gender disparity in stroke thrombectomy outcomes. J Neurointerv Surg. (2018) 10:949–52. doi: 10.1136/neurintsurg-2017-013697,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 14.

  Ciurică S Lopez-Sublet M Loeys BL Radhouani I Natarajan N Vikkula M et al . Arterial tortuosity. Hypertension. (2019) 73:951–60. doi: 10.1161/hypertensionaha.118.11647

  • CrossRef
  • Google Scholar

• 15.

  Al-Rukn S Mazya M Akhtar N Hashim H Mansouri B Faouzi B et al . Stroke in the middle-east and North Africa: a 2-year prospective observational study of intravenous thrombolysis treatment in the region. Results from the SITS-MENA registry. Int J Stroke. (2020) 15:980–7. doi: 10.1177/1747493019874729,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 16.

  Madsen TE DeCroce-Movson E Hemendinger M McTaggart RA Yaghi S Cutting S et al . Sex differences in 90-day outcomes after mechanical thrombectomy for acute ischemic stroke. J Neurointerv Surg. (2019) 11:221–5. doi: 10.1136/neurintsurg-2018-014050,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 17.

  Abdalkader M Ning S Qureshi MM Haussen DC Strbian D Nagel S et al . Sex differences in outcomes of late-window endovascular stroke therapy. Stroke. (2024) 55:278–87. doi: 10.1161/strokeaha.123.045015,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 18.

  Tan BYQ Siow I Lee KS Chen V Ong N Gopinathan A et al . Effect of sex on outcomes of mechanical thrombectomy in basilar artery occlusion: a multicentre cohort study. Cerebrovasc Dis. (2022) 51:639–46. doi: 10.1159/000524048,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 19.

  Zi W Qiu Z Li F Sang H Wu D Luo W et al . Effect of endovascular treatment alone vs intravenous alteplase plus endovascular treatment on functional Independence in patients with acute ischemic stroke: the DEVT randomized clinical trial. JAMA. (2021) 325:234–43. doi: 10.1001/jama.2020.23523,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 20.

  Qiu Z Li F Sang H Luo W Liu S Liu W et al . Effect of intravenous tirofiban vs placebo before endovascular thrombectomy on functional outcomes in large vessel occlusion stroke: the RESCUE BT randomized clinical trial. JAMA. (2022) 328:543–53. doi: 10.1001/jama.2022.12584,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 21.

  Yang Q Guo C Yue C Song J Yang J Peng Z et al . Methylprednisolone as adjunct to endovascular thrombectomy for large-vessel occlusion stroke: the MARVEL randomized clinical trial. JAMA. (2024) 331:840–9. doi: 10.1001/jama.2024.0626,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 22.

  Adams HP Jr Bendixen BH Kappelle LJ Biller J Love BB Gordon DL et al . Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of org 10172 in acute stroke treatment. Stroke. (1993) 24:35–41. doi: 10.1161/01.str.24.1.35,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 23.

  Kwah LK Diong J . National Institutes of Health stroke scale (NIHSS). J Physiother. (2014) 60:61. doi: 10.1016/j.jphys.2013.12.012,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 24.

  Higashida RT Furlan AJ Roberts H Tomsick T Connors B Barr J et al . Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke. Stroke. (2003) 34:e109–37. doi: 10.1161/01.Str.0000082721.62796.09,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 25.

  Barber PA Demchuk AM Zhang J Buchan AM . Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. ASPECTS study group. Alberta stroke programme early CT score. Lancet. (2000) 355:1670–4. doi: 10.1016/s0140-6736(00)02237-6

  • CrossRef
  • Google Scholar

• 26.

  Liebeskind DS Bracard S Guillemin F Jahan R Jovin TG Majoie CB et al . eTICI reperfusion: defining success in endovascular stroke therapy. J Neurointerv Surg. (2019) 11:433–8. doi: 10.1136/neurintsurg-2018-014127,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 27.

  Banks JL Marotta CA . Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis. Stroke. (2007) 38:1091–6. doi: 10.1161/01.STR.0000258355.23810.c6,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 28.

  von Kummer R Broderick JP Campbell BC Demchuk A Goyal M Hill MD et al . The Heidelberg bleeding classification: classification of bleeding events after ischemic stroke and reperfusion therapy. Stroke. (2015) 46:2981–6. doi: 10.1161/strokeaha.115.010049

  • CrossRef
  • Google Scholar

• 29.

  Ospel J Singh N Ganesh A Goyal M . Sex and gender differences in stroke and their practical implications in acute care. J Stroke. (2023) 25:16–25. doi: 10.5853/jos.2022.04077,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 30.

  Sun D Raynald Huo X Jia B Tong X Ma G et al . Sex-related differences in outcomes of endovascular treatment for anterior circulation large vessel occlusion. Stroke. (2023) 54:327–36. doi: 10.1161/strokeaha.122.041195

  • CrossRef
  • Google Scholar

• 31.

  Bushnell C Howard VJ Lisabeth L Caso V Gall S Kleindorfer D et al . Sex differences in the evaluation and treatment of acute ischaemic stroke. Lancet Neurol. (2018) 17:641–50. doi: 10.1016/s1474-4422(18)30201-1,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 32.

  Deb-Chatterji M Schlemm E Flottmann F Meyer L Alegiani A Brekenfeld C et al . Sex differences in outcome after thrombectomy for acute ischemic stroke are explained by confounding factors. Clin Neuroradiol. (2021) 31:1101–9. doi: 10.1007/s00062-020-00983-2,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 33.

  Honigberg MC Zekavat SM Aragam K Finneran P Klarin D Bhatt DL et al . Association of Premature Natural and Surgical Menopause with Incident Cardiovascular Disease. JAMA. (2019) 322:2411–21. doi: 10.1001/jama.2019.19191,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 34.

  Bushnell C McCullough LD Awad IA Chireau MV Fedder WN Furie KL et al . Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. (2014) 45:1545–88. doi: 10.1161/01.str.0000442009.06663.48,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 35.

  Mansoor H Elgendy IY Segal R Hartzema A . Duration of reproductive years and the risk of cardiovascular and cerebrovascular events in older women: insights from the National Health and nutrition examination survey. J Womens Health (Larchmt). (2017) 26:1047–52. doi: 10.1089/jwh.2016.6013,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 36.

  Elgendy IY Mansoor H Pepine CJ . Reproductive lifespan and incident stroke risk among post-menopausal women: is it time for sex-specific risk prediction tools?Int J Cardiol. (2021) 328:218–9. doi: 10.1016/j.ijcard.2020.12.032,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 37.

  Chalos V de Ridder IR Lingsma HF Brown S van Oostenbrugge RJ Goyal M et al . Does sex modify the effect of endovascular treatment for ischemic stroke?Stroke. (2019) 50:2413–9. doi: 10.1161/strokeaha.118.023743,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 38.

  Bala F Casetta I Nannoni S Herlihy D Goyal M Fainardi E et al . Sex-related differences in outcomes after endovascular treatment of patients with late-window stroke. Stroke. (2022) 53:311–8. doi: 10.1161/strokeaha.121.037127,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 39.

  Marko M Miksova D Haidegger M Schneider J Ebner J Lang MB et al . Trends in sex differences of functional outcome after intravenous thrombolysis in patients with acute ischemic stroke. Int J Stroke. (2024) 19:1147–54. doi: 10.1177/17474930241273696,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 40.

  Pandie S Mehta SR Cantor WJ Cheema AN Gao P Madan M et al . Radial versus femoral access for coronary angiography/intervention in women with acute coronary syndromes: insights from the RIVAL trial (radial vs femorAL access for coronary intervention). JACC Cardiovasc Interv. (2015) 8:505–12. doi: 10.1016/j.jcin.2014.11.017,

  • Pubmed Abstract
  • CrossRef
  • Google Scholar