The impact of sex on stroke care: From epidemiology to outcome.

BACKGROUND: Carotid stenosis and atrial fibrillation are key risk factors for development of hemispheric strokes. In this review we aim to identify sex-specific differences in the pathophysiology and treatment of these risk factors and areas for future study. KEY FINDINGS: Women are underrepresented in research studies of stroke in patients with carotid disease and atrial fibrillation. However, key differences have been found between men and women that suggest that the development of carotid disease and atrial fibrillation occur at later stages of life and are associated with higher severity of stroke. Some treatments, including surgical treatment, seem to have different rates of efficacy and women and women are at higher risk of surgical complications. This suggests that treatment recommendations may need to be sex specific. CONCLUSION: Efforts should be made to address research and treatment gaps in women with stroke risk factors. This may lead to the development of sex-specific recommendations for stroke prevention and treatment.

Optimal Angiographic Goal and Number of Passes for Octogenarians Undergoing Endovascular Stroke Thrombectomy.

BACKGROUND: The optimal recanalization goal and number of endovascular thrombectomy (EVT) passes for elderly patients with large vessel occlusion strokes is unclear. METHODS: Consecutive patients 80 years or older undergoing EVT were identified from 2016 to 2022 at a single center. Clinical information, procedural details, and modified treatment in cerebral ischemia (mTICI) scores were collected. Primary outcome was modified Rankin scale (mRS) at 90 days. Bivariate and multivariable analyses were conducted to assess associations between mTICI scores, EVT passes, and 90-day outcomes. RESULTS: One hundred twenty-six patients were identified. At 90 days, mTICI 2b recanalization resulted in high rates of poor outcomes (8.7% functional independence and 60.9% mortality) not significantly different from mTICI 0, 1 or 2a (median mRS 6 vs. 6, P = 0.61). Complete recanalization (mTICI 2c or 3) led to significantly better mRS outcomes at 90 days compared to mTICI 2b (median mRS 4 vs. 6, adjusted P = 0.038), with 26.8% functional independence and 37.8% mortality. In multivariable analysis, complete recanalization was significantly associated with better 90-day outcomes than mTICI 2b or lower recanalization (odds ratio 4.24 [95% Confidence interval 1.46-12.3]; P = 0.002), while the number of passes was not independently associated with worse outcomes (P = 0.98). CONCLUSIONS: For octogenarians, mTICI 2b recanalization yields limited clinical benefit and results in poor 90-day outcomes. In contrast, complete recanalization is independently associated with significantly better outcomes. Thus, once the decision is made to pursue EVT in the elderly, mTICI 2c or better recanalization should be the angiographic goal. Providers should not withhold thrombectomy passes based on age alone.

Mildly elevated INR is associated with worse outcomes following mechanical thrombectomy for acute ischemic stroke.

BACKGROUND: Elevated International Normalized Ratio (INR) is a marker of coagulopathy, but its impact on outcomes following mechanical thrombectomy (MT) in patients with stroke is unclear. This study investigates the impact of mild INR elevations on clinical outcomes following MT. METHODS: In this retrospective cohort study, consecutive patients with stroke treated with MT were identified from 2015 to 2020 at a Comprehensive Stroke Center. Demographic information, past medical history, INR, National Institutes of Health Stroke Scale score, use of tissue plasminogen activator, and last known normal to arteriotomy time were recorded. Outcome measures included modified Thrombolysis in Cerebral Infarction (mTICI) score, modified Rankin Scale (mRS) score at 90 days, and intracerebral hemorrhage (ICH). Patients were divided into two groups: normal INR (0.8-1.1) and mildly elevated INR (1.2-1.7). RESULTS: A total of 489 patients were included for analysis, of which 349 had normal INR and 140 had mildly elevated INR. After multivariable adjustments, mildly elevated INR was associated with lower odds of excellent outcomes (mRS 0-1, OR 0.24, p=0.009), lower odds of functional independence (mRS 0-2, OR 0.38, p=0.038), and higher odds of 90-day mortality (OR 3.45, p=0.018). Elevated INR was not associated with a higher likelihood of ICH, and there were no differences in rates of HI1, HI2, PH1, or PH2 hemorrhagic transformations; however, elevated INR was associated with significantly higher odds of 90-day mortality in patients with ICH (OR 6.22, p=0.024). This effect size was larger than in patients without ICH (OR 3.38, p<0.001). CONCLUSION: In patients with stroke treated with MT, mildly elevated INR is associated with worse clinical outcomes after recanalization and may worsen the mortality risk of hemorrhagic transformations.

Trends in age and sex-specific prevalence of cancer and cancer subtypes in acute ischemic stroke from 2007-2019.

OBJECTIVE: To describe age and sex-specific prevalence of cancer in acute ischemic stroke (AIS) hospitalizations in the United States over the last decade. METHODS: We conducted a retrospective serial cross-sectional study using all primary AIS discharges (weighted n=5,748,358) with and without cancer in the 2007-2019 National Inpatient Sample. Admissions with primary central nervous system cancers were excluded. Joinpoint regression was used to compute the average annualized percentage change (AAPC) in cancer prevalence over time. RESULTS: Across the study period, 12.7% of AIS admissions had previous/active cancer, while 4.4% had active cancer. Of these, 18.8% were hematologic cancers, 47.2% were solid cancers without metastasis and 34.0% were metastatic cancers of any type. Age-adjusted active cancer prevalence differed by sex (males:4.8%; females:4.0%) and increased with age up to age 70-79 years (30-39 years 1.4%; 70-79 years:5.7%). Amongst cancer admissions, lung (18.7%) and prostate (17.8%) were the most common solid cancers in men, while lung (19.6%) and breast (13.7%) were the most prevalent in women. Active cancer prevalence increased over time (AAPC 1.7%, p<0.05) but the pace of increase was significantly faster in women (AAPC 2.8%) compared to men (AAPC 1.1%) (p-comparison =0.003). Fastest pace of increased prevalence was seen for genitourinary cancers in women and for gastrointestinal cancers in both sexes. Genitourinary cancers in men declined over time (AAPC -2.5%, p<0.05). Lung cancer prevalence increased in women (AAPC 1.8%, p<0.05) but remained constant in men. Prevalence of head/neck, skin/bone, gastrointestinal, hematological and metastatic cancers increased over time at similar pace in both sexes. CONCLUSION: Prevalence of cancer in AIS admissions increased in the US over the last decade but the pace of this increase was faster in women compared to men. Gastrointestinal cancers in both sexes and genitourinary cancers in women are increasing at the fastest pace. Additional studies are needed to determine whether this increase is from co-occurrence or causation of AIS by cancer.

Black-white Differences in Left Ventricular Hypertrophy Rates Among Young Adults with Ischemic Stroke.

OBJECTIVES: Few studies have addressed Black-White differences in left ventricular hypertrophy (LVH) in young stroke patients without a history of hypertension. METHODS: A case-only cross-sectional analysis performed in 2019 of data from the Stroke Prevention in Young Adults Study, a population-based case-control study of ischemic stroke patients ages 15-49. The main outcomes were hypertension indicators at the time of stroke hospitalization: self-reported history of hypertension, LVH by echocardiography (Echo-LVH) and LVH by electrocardiogram (ECG-LVH). The prevalence of Echo-LVH was further determined in those with and without a history of hypertension. Adjusted odds ratios and 95% confidence intervals comparing blacks and whites were calculated by logistic regression. RESULTS: The study population included 1028 early-onset ischemic stroke patients, 48% Black cases, 54% men, median age 43 years (interquartile range, 38-46 years). Overall, the prevalence of hypertension history, Echo-LVH and ECG-LVH were 41.3%, 34.1% and 17.5%, respectively. Each of the hypertension indicators were more frequent in men than in women and in Black cases than in White cases. Black patients without a history of hypertension had higher rates of Echo-LVH than their white counterparts, 40.3% vs 27.7% (age and obesity adjusted OR 1.8; 95% CI 1.02-3.4) among men and 20.9% vs 7.6% (adjusted OR 2.7; 95% CI 1.2-6.2) among women. CONCLUSIONS: LVH was common in young patients with ischemic stroke, regardless of self-reported history of hypertension. These findings emphasize the need for earlier screening and more effective treatment of hypertension in young adults, particularly in the Black population.

Differences in Multiple Risk Factors Between Black and White Individuals With Young-Onset Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Stroke in young adults constitutes 15%-18% of all ischemic stroke cases. Black individuals have an excess risk of ischemic stroke especially in young adults. Although it is known that Black patients have a higher prevalence of hypertension and diabetes, few studies have addressed the association of concurrent multiple vascular risk factors with the excess risk of early-onset stroke among Black individuals. METHODS: A population-based case-control study of early-onset ischemic stroke, ages 15-49 years, was conducted in the Baltimore-Washington DC region between 1992 and 2007. Presence of the risk factors of obesity, hypertension, diabetes, and current smoking were obtained from both cases and controls by an in-person interview. Risk factor groups were defined as (1) 1 risk factor, (2) 2 risk factors, (3) 3 risk factors, and (4) 4 risk factors. Logistic regression analysis adjusting for age and sex was used to evaluate the association between each risk factor group and ischemic stroke compared with the reference group with no risk factors. RESULTS: The study included 1,034 cases and 1,091 controls. Of the cases, 47% were Black, 54% were men, and the mean (±SD) age was 41.0 (±6.9) years. The odds of having a stroke increased exponentially as the number of risk factors increased, 2.1, 2.6, 7.6, 16.5, all p < 0.001, for groups 1-4, respectively. When stratified by race, Black individuals were approximately 6 times more likely to have all 4 risk factors. DISCUSSION: The risk of stroke in young adults increased exponentially with the number of risk factors. Young Black patients with ischemic stroke were approximately 6 times more likely to have the co-occurrence of obesity, hypertension, diabetes, and smoking compared with their White counterparts. Targeting public health interventions to identify and improve care to Black young adults with multiple stroke risk factors may have substantial impact on lowering risk of stroke.

Black-White Differences in Ischemic Stroke Risk Factor Burden in Young Adults.

BACKGROUND AND PURPOSE: Although the US Black population has a higher incidence of stroke compared with the US White population, few studies have addressed Black-White differences in the contribution of vascular risk factors to the population burden of ischemic stroke in young adults. METHODS: A population-based case-control study of early-onset ischemic stroke, ages 15 to 49 years, was conducted in the Baltimore-Washington DC region between 1992 and 2007. Risk factor data was obtained by in-person interview in both cases and controls. The prevalence, odds ratio, and population-attributable risk percent (PAR%) of smoking, diabetes, and hypertension was determined among Black patients and White patients, stratified by sex. RESULTS: The study included 1044 cases and 1099 controls. Of the cases, 47% were Black patients, 54% were men, and the mean (±SD) age was 41.0 (±6.8) years. For smoking, the population-attributable risk percent were White men 19.7%, White women 32.5%, Black men 10.1%, and Black women 23.8%. For diabetes, the population-attributable risk percent were White men 10.5%, White women 7.4%, Black men 17.2%, and Black women 13.4%. For hypertension, the population-attributable risk percent were White men 17.2%, White women 19.3%, Black men 45.8%, and Black women 26.4%. CONCLUSIONS: Modifiable vascular risk factors account for a large proportion of ischemic stroke in young adults. Cigarette smoking was the strongest contributor to stroke among White patients while hypertension was the strongest contributor to stroke among Black patients. These results support early primary prevention efforts focused on smoking cessation and hypertension detection and treatment.

Optimizing the Recognition and Treatment of In-Hospital Stroke: Evaluation of the 2CAN Score.

OBJECTIVES: Stroke-like symptoms may be difficult to appreciate due to the high incidence of stroke mimics (e.g., delirium) in the inpatient population. Many centers have adopted inpatient-specific stroke protocols with the aim of improving time to diagnosis and treatment. We aimed to assess one of these instruments, the "2CAN" score, in our patient population. MATERIALS AND METHODS: A retrospective chart review was conducted for all inpatients for whom our Brain Attack Team (BAT) was called between January 2015 and June 2019. Patients were excluded if they had stroke prior to current admission, were in the emergency department at the time of BAT call, or had incomplete documentation. The 2CAN score was calculated for each patient. RESULTS: The BAT was activated 201 times, and 110 patients met inclusion criteria. Twenty percent of patients had a history of atrial fibrillation, 72% hypertension, and 36% diabetes. Median NIHSS was 14.5 (IQR 5-24). Only 18% of stroke calls occurred within 24 h of hospital admission. The mean 2CAN score was 2.8. Ninety-seven (88%) patients received a final diagnosis of ischemic stroke and 13 (12%) of stroke mimics. There was no difference between 2CAN scores in the stroke and mimic groups (P = 0.91). A 2CAN score of ≥ 2 had sensitivity 83.5%, specificity 23.1%, PPV 89.0%, and NPV 15.8% for stroke. CONCLUSIONS: The 2CAN score was derived and validated in a single academic center as a tool to recognize inpatient stroke. The 2CAN score had good sensitivity and positive predictive value for stroke in our cohort, but poor specificity.

Marijuana Use and the Risk of Early Ischemic Stroke: The Stroke Prevention in Young Adults Study.

BACKGROUND AND PURPOSE: Few studies have examined the dose-response and temporal relationships between marijuana use and ischemic stroke while controlling for important confounders, including the amount of tobacco smoking. The purpose of our study was to address these knowledge gaps. METHODS: A population-based case-control study with 1090 cases and 1152 controls was used to investigate the relationship of marijuana use and early-onset ischemic stroke. Cases were first-ever ischemic stroke between the ages of 15 and 49 identified from 59 hospitals in the Baltimore-Washington region. Controls obtained by random digit dialing from the same geographic region were frequency-matched to cases by age, sex, region of residence and, except for the initial study phase, race. After excluding subjects with cocaine and other vasoactive substance use, the final study sample consisted of 751 cases and 813 controls. All participants underwent standardized interviews to characterize stroke risk factors and marijuana use. Unconditional logistic regression analysis was used to assess the relationships between marijuana use and risk of ischemic stroke, adjusting for age, sex, race, study phase, the amount of current tobacco smoking, current alcohol use, hypertension, and diabetes. RESULTS: After adjusting for other risk factors, including the amount of current tobacco smoking, marijuana use was not associated with ischemic stroke, regardless of the timing of use in relationship to the stroke, including ever use, use within 30 days, and use within 24 hours. There was a nonsignificant trend towards increased stroke risk among those who smoked marijuana at least once a week (odds ratio, 1.9 [95% CI, 0.8-4.9]). CONCLUSIONS: These analyses do not demonstrate an association between marijuana use and an increased risk of early-onset ischemic stroke, although statistical power was limited for assessing the association among very heavy users.

Sickle Cell Trait and Risk of Ischemic Stroke in Young Adults.

BACKGROUND AND PURPOSE: Approximately 8% of Blacks have sickle cell trait (SCT), and there are conflicting reports from recent cohort studies on the association of SCT with ischemic stroke (IS). Most prior studies focused on older populations, with few data available in young adults. METHODS: A population-based case-control study of early-onset IS was conducted in the Baltimore-Washington region between 1992 and 2007. From this study, 342 Black IS cases, ages 15 to 49, and 333 controls without IS were used to examine the association between SCT and IS. Each participant's SCT status was established by genotyping and imputation. For analysis, χ2 tests and logistic regression models were performed with adjustment for potential confounding variables. RESULTS: Participants with SCT (n=55) did not differ from those without SCT (n=620) in prevalence of hypertension, previous myocardial infarction, diabetes mellitus, and current smoking status. Stroke cases had increased prevalence in these risk factors compared with controls. We did not find an association between SCT and early-onset IS in our overall population (odds ratio=0.9 [95% CI, 0.5-1.7]) or stratified by sex in males (odds ratio=1.26 [95% CI, 0.56-2.80]) and females (odds ratio=0.67 [95% CI, 0.28-1.69]). CONCLUSIONS: Our data did not find evidence of increased risk of early-onset stroke with SCT.

Screening individuals with intracranial aneurysms for abdominal aortic aneurysms is cost-effective based on estimated coprevalence.

OBJECTIVE: Aneurysm rupture is a major cause of morbidity and mortality, and evidence suggests shared risk for both abdominal aortic aneurysms (AAAs) and intracranial aneurysms (IAs). We hypothesized that screening for AAA in patients with known IA is cost-effective. METHODS: We used a decision tree model to compare costs and outcomes of AAA screening vs no screening in a hypothetical cohort of patients with IA. We measured expected outcomes using quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER). We performed a Monte Carlo simulation and additional sensitivity analyses to assess the effects of ranging base case variables on model outcomes and identified thresholds where a decision alternative dominated the model (both less expensive and more effective than the alternative). RESULTS: In our base case analysis, screening for AAA provided an additional 0.17 QALY (2.5-97.5 percentile: 0.11-0.27 QALY) at a saving of $201 (2.5-97.5 percentile: $-127 to $896). This yielded an ICER of $-1150/QALY (2.5-97.5 percentile: $-4299 to $6374/QALY), that is, screening saves $1150 per QALY gained. CONCLUSIONS: Based on this model, screening for AAA in individuals with IA is cost-effective at an ICER of $1150/QALY, well below accepted societal thresholds estimated at $60,000/QALY. Cost-effectiveness of cross-screening in these populations is sensitive to aneurysm coprevalence and risk of rupture. Further prospective study is warranted to validate this finding.

Human prion diseases: surgical lessons learned from iatrogenic prion transmission.

The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood "infectious protein" has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Interestingly, since their discovery, there have been more than 492 incidents of iatrogenic transmission of prion diseases, largely resulting from prion-contaminated growth hormone and dura mater grafts. Although fewer than 9 cases of probable iatrogenic neurosurgical cases of Creutzfeldt-Jakob disease (CJD) have been reported worldwide, the likelihood of some missed cases and the potential for prion transmission by neurosurgery create considerable concern. Laboratory studies indicate that standard decontamination and sterilization procedures may be insufficient to completely remove infectivity from prion-contaminated instruments. In this unfortunate event, the instruments may transmit the prion disease to others. Much caution therefore should be taken in the absence of strong evidence against the presence of a prion disease in a neurosurgical patient. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have devised risk assessment and decontamination protocols for the prevention of iatrogenic transmission of the prion diseases, incidents of possible exposure to prions have unfortunately occurred in the United States. In this article, the authors outline the historical discoveries that led from kuru to the identification and isolation of the pathological prion proteins in addition to providing a brief description of human prion diseases and iatrogenic forms of CJD, a brief history of prion disease nosocomial transmission, and a summary of the CDC and WHO guidelines for prevention of prion disease transmission and decontamination of prion-contaminated neurosurgical instruments.

A low-cost, tablet-based option for prehospital neurologic assessment: The iTREAT Study.

OBJECTIVES: In this 2-center study, we assessed the technical feasibility and reliability of a low cost, tablet-based mobile telestroke option for ambulance transport and hypothesized that the NIH Stroke Scale (NIHSS) could be performed with similar reliability between remote and bedside examinations. METHODS: We piloted our mobile telemedicine system in 2 geographic regions, central Virginia and the San Francisco Bay Area, utilizing commercial cellular networks for videoconferencing transmission. Standardized patients portrayed scripted stroke scenarios during ambulance transport and were evaluated by independent raters comparing bedside to remote mobile telestroke assessments. We used a mixed-effects regression model to determine intraclass correlation of the NIHSS between bedside and remote examinations (95% confidence interval). RESULTS: We conducted 27 ambulance runs at both sites and successfully completed the NIHSS for all prehospital assessments without prohibitive technical interruption. The mean difference between bedside (face-to-face) and remote (video) NIHSS scores was 0.25 (1.00 to -0.50). Overall, correlation of the NIHSS between bedside and mobile telestroke assessments was 0.96 (0.92-0.98). In the mixed-effects regression model, there were no statistically significant differences accounting for method of evaluation or differences between sites. CONCLUSIONS: Utilizing a low-cost, tablet-based platform and commercial cellular networks, we can reliably perform prehospital neurologic assessments in both rural and urban settings. Further research is needed to establish the reliability and validity of prehospital mobile telestroke assessment in live patients presenting with acute neurologic symptoms.

Shared genetic susceptibility of vascular-related biomarkers with ischemic and recurrent stroke.

OBJECTIVE: To investigate the genetic contributors to cerebrovascular disease and variation in biomarkers of ischemic stroke. METHODS: The Vitamin Intervention for Stroke Prevention Trial (VISP) was a randomized, controlled clinical trial of B vitamin supplementation to prevent recurrent stroke, myocardial infarction, or death. VISP collected baseline measures of C-reactive protein (CRP), fibrinogen, creatinine, prothrombin fragments F1+2, thrombin-antithrombin complex, and thrombomodulin prior to treatment initiation. Genome-wide association scans were conducted for these traits and follow-up replication analyses were performed. RESULTS: We detected an association between CRP single nucleotide polymorphisms (SNPs) and circulating CRP levels (most associated SNP, rs2592902, p = 1.14 × 10(-9)) in 2,100 VISP participants. We discovered a novel association for CRP level in the AKR1D1 locus (rs2589998, p = 7.3 × 10(-8), approaching genome-wide significance) that also is an expression quantitative trait locus for CRP gene expression. We replicated previously identified associations of fibrinogen with SNPs in the FGB and LEPR loci. CRP-associated SNPs and CRP levels were significantly associated with risk of ischemic stroke and recurrent stroke in VISP as well as specific stroke subtypes in METASTROKE. Fibrinogen levels but not fibrinogen-associated SNPs were also found to be associated with recurrent stroke in VISP. CONCLUSIONS: Our data identify a genetic contribution to inflammatory and hemostatic biomarkers in a stroke population. Additionally, our results suggest shared genetic contributions to circulating CRP levels measured poststroke and risk for incident and recurrent ischemic stroke. These data broaden our understanding of genetic contributors to biomarker variation and ischemic stroke risk, which should be useful in clinical risk evaluation.

Prevalence of dural venous sinus stenosis and hypoplasia in a generalized population.

BACKGROUND AND PURPOSE: While recent literature has described the prevalence of transverse sinus stenosis in patients with idiopathic intracranial hypertension, tinnitus, and refractory headaches, it is unclear what the prevalence is in the general population. This study evaluates the prevalence of venous sinus stenosis and hypoplasia in the general patient population. MATERIALS AND METHODS: 355 of 600 consecutive patients who underwent CT angiography of the head met the inclusion criteria. The diameters of the dural venous sinuses were recorded. Each study was evaluated by a neuroradiologist for the presence of stenoses. Univariate and multivariate statistical analyses were performed by a statistician. RESULTS: The prevalence of unilateral transverse sinus stenosis or hypoplasia in a sample of patients representing the general population was 33%, the prevalence of bilateral transverse sinus stenosis was 5%, and the prevalence of unilateral stenosis with contralateral hypoplasia was 1%. A multivariate analysis identified arachnoid granulations as a predictor of stenosis (p<0.001). Gender trended toward significance (p=0.094). Race was not a significant predictor of stenosis (p=0.745). CONCLUSIONS: The prevalence of bilateral transverse sinus stenosis in the general population is not trivial. These data may be used as a reference for understanding the mechanistic role of stenoses in idiopathic intracranial hypertension, tinnitus, and refractory headaches.

Endovascular vs medical management of acute ischemic stroke.

OBJECTIVE: To compare the outcomes between endovascular and medical management of acute ischemic stroke in recent randomized controlled trials (RCT). METHODS: A systematic literature review was performed, and multicenter, prospective RCTs published from January 1, 2013, to May 1, 2015, directly comparing endovascular therapy to medical management for patients with acute ischemic stroke were included. Meta-analyses of modified Rankin Scale (mRS) and mortality at 90 days and symptomatic intracranial hemorrhage (sICH) for endovascular therapy and medical management were performed. RESULTS: Eight multicenter, prospective RCTs (Interventional Management of Stroke [IMS] III, Local Versus Systemic Thrombolysis for Acute Ischemic Stroke [SYNTHESIS] Expansion, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy [MR RESCUE], Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands [MR CLEAN], Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness [ESCAPE], Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial [EXTEND-IA], Solitaire With the Intention For Thrombectomy as Primary Endovascular Treatment [SWIFT PRIME], and Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours [REVASCAT]) comprising 2,423 patients were included. Meta-analysis of pooled data demonstrated functional independence (mRS 0-2) at 90 days in favor of endovascular therapy (odds ratio [OR] = 1.71; p = 0.005). Subgroup analysis of the 6 trials with large vessel occlusion (LVO) criteria also demonstrated functional independence at 90 days in favor of endovascular therapy (OR = 2.23; p < 0.00001). Subgroup analysis of the 5 trials that primarily utilized stent retriever devices (≥70%) in the intervention arm demonstrated functional independence at 90 days in favor of endovascular therapy (OR = 2.39; p < 0.00001). No difference was found for mortality at 90 days and sICH between endovascular therapy and medical management in all analyses and subgroup analyses. CONCLUSIONS: This meta-analysis provides strong evidence that endovascular intervention combined with medical management, including IV tissue plasminogen activator for eligible patients, improves the outcomes of appropriately selected patients with acute ischemic stroke in the setting of LVO.