Acute ischemic stroke (AIS) due to large vessel occlusion (LVO) continues to be one of the leading causes of mortality and morbidity worldwide. Currently, mechanical thrombectomy (MT) is recommended as the first-line therapy for AIS-LVO involving the anterior circulation.1 However, there is significant controversy regarding sex-specific stroke outcomes, with focus on biological, genetic, and socioeconomic contributors. Whether sex influences the outcomes after MT has been previously debated based on data from randomized clinical trials (RCTs). Most recently, a subgroup analysis of HERMES (Highly Effective Reperfusion Using Multiple Endovascular Devices) collaborators, analyzing 1762 patients from 7 RCTs, showed no influence of sex on clinical outcome after MT.2
It is been generally accepted that trial populations are different from real-world patient cohorts due to the strict exclusion criteria of clinical trials for the benefit of investigational treatment.3 Therefore, it is largely unknown whether sex impacts MT outcomes for AIS-LVO in 'real world’ populations. There are several studies which attempt to clarify this issue in the real-world setting, and conflicting results are noted. Although some studies showed a negative impact of male sex on outcome,3-5 others demonstrated female patients are less likely to benefit from MT than male patients.6, 7 Additionally, related research in Asian countries is rare. In a Japanese prospective registry, it was reported that female patients were less likely to receive endovascular therapy than male patients (47.9% versus 57.7%, p<0.001). Thus, clarifying the impact of sex on MT outcomes is critical to provide updated clinical evidence regarding the role of sex-specific treatment decisions and to guide future research. In this study, we investigated the impact of sex on functional outcomes after MT based on an Asian non-clinical trial population and performed a systematic review and meta-analysis based on published literature in real-world settings.
AIS-LVO patients with anterior circulation occlusions who received MT from our tertiary care academic institution from January 2019 to December 2021 were retrospectively reviewed. Patients were included based on the following inclusion criteria: (1) age ≥18 years); (2) AIS-LVO in the anterior circulation; (3) premorbid modified Rankin scale (mRS) score 0-2 before stroke onset; (4) baseline National Institutes of Health Stroke Scale (NIHSS) score ≥6; (5) baseline Alberta Stroke Program Early CT score (ASPECTS) 6-10 based on non-contrast CT scan; (6) onset to puncture time within 24 hours. We excluded patients not meeting these inclusion criteria as well as patients with concomitant ICH before MT, poor imaging quality and incomplete follow-up data. This study was approved by the institutional review board, and the need for written informed consent was waived due to its retrospective nature and minimal patient risk.
Study variables and covariates
Clinical, procedural, and imaging data were collected, including age, sex, comorbidities (hypertension [HTN], diabetes mellitus [DM], coronary artery disease [CAD], etc.), baseline NIHSS, stroke type according to the Trial of Org 10172 in Acute Stroke Treatment classification (TOAST), intravenous thrombolysis, anesthesia type, time from onset to recanalization (OTR), etc. Results of routine biochemical examination before MT were also documented, including complete blood cell count (account of neutrophil, lymphocyte, platelet, neutrophil to lymphocyte ratio [NLR], platelet to lymphocyte ratio [PLR]), comprehensive metabolic panel and lipid panel (glucose, triglyceride [TG], total cholesterol [TC], high-density lipoprotein [HDL], low-density lipoprotein [LDL], etc.).
Imaging data included baseline ASPECTS from noncontrast computed tomography (NCCT) and occlusion site, which was diagnosed from initial CTA and confirmed with digital subtraction angiography (DSA). Collateral status was assed using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral grading system and collateral status was dichotomized into poor (ASITN/SIR 0–2) or good (ASITN/SIR 3–4).8 Recanalization status was evaluated using the modified Thrombolysis in Cerebral Infarction (mTICI) score, with mTICI 2b-3 defined as successful recanalization.
The primary study endpoint was favorable outcome, defined as 90-day mRS 0-2. Secondary outcomes were 90-day mortality, ICH and symptomatic hemorrhage (sICH). The definition of sICH was follow-up imaging evidence of hemorrhagic transformation with NIHSS increase ≥4 according to the European-Australian Cooperative Acute Stroke Study II [ECASS II]).9 Imaging examinations, including NCCT and MRI (if available) were separately reviewed and analyzed by two independent experienced radiologists (FY and AS).
Patients were classified as female or male. Baseline characteristics were analyzed and compared between the two groups using descriptive statistics. For qualitative variables, data were compared using the χ2 and Fisher’s exact tests when appropriate; for quantitative variables, data were compared using the two-sided unpaired Student t and the Mann–Whitney U tests when appropriate. Normality of quantitative variables was determined by the Shapiro–Wilk test. A logistic regression model was performed to assess whether sex impacts the outcome after MT. These models were subsequently adjusted for the following variables: age, AF, history of smoking, history of drinking, history of stroke, anticoagulation use, NIHSS score, TOAST classification, PLR, glucose, HDL, apoA, platelet count, and mTICI status. All calculations were performed using SAS software, version 9.4 (SAS Institute Inc, Cary, NC, USA). A value of p<0.05 was considered statistically significant.
We further conducted a systematic review and meta-analysis of previous studies, combined with our collected data, to explore the impact of sex on MT outcomes in a real-world setting. This project has been registered on the PROSPERO database (https://www.crd.york.ac.uk/prospero/) with the registration number as CRD42021242597. The protocol of this systematic review and meta-analysis regarding the details of methods has been published previously.10 The databases searched were Medline (Ovid), Science Citation Index Expanded (SCI-EXPANDED), Embase, and the Cochrane Library. Relevant observational studies published in English from January 1st, 2015 to March 1st, 2022 were searched. Key terms included acute ischemic stroke, mechanical thrombectomy, stent retrieval thrombectomy, stent retriever, sex, female, male, etc. (further details are in the supplementary methods). Studies included in this systematic review were non-RCT studies, including case–control studies, cohort studies and registry studies. Conference abstracts, reviews, meta-analyses, and case reports were excluded.