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.

The BAND score: A simple model for upfront prediction of poor outcomes despite successful stroke thrombectomy.

BACKGROUND: While endovascular thrombectomy (EVT) is beneficial for patients with acute large vessel occlusion ischemic strokes, a significant portion of patients still do poorly despite successful recanalization. Identifying patients at high risk for poor outcomes can be helpful for future clinical trial design and optimizing acute stroke triage. METHODS: Consecutive EVT patients were identified from 2016 to 2021 at a Comprehensive Stroke Center, and clinical information was recorded. Poor outcome was defined as a 90-day modified Rankin Scale (mRS) of 4 or greater despite achieving a modified thrombolysis in cerebral infarction (mTICI) score of 2b or greater. Multivariable regression analyses were used to identify risk factors for poor outcomes, and a scoring system was constructed. RESULTS: 483 patients with successful recanalization were identified. From a randomly selected training cohort (n = 357), the 10-point BAND score was constructed from independent risk factors for poor outcomes: baseline disability (1 point: baseline mRS ≥ 2), age (1 point: 60-69 years, 2 points: 70-79 years, 3 points: 80-84 years, 4 points: 85 years or older), NIHSS (2 points: 13-17, 3 points: 18-22, and 4 points: ≥ 23), and delay from last known normal (1 point: ≥ 6 h). The BAND score was significantly associated with rates of poor outcomes (p < 0.001), and it achieved an area under the receiver-operating characteristic curve (AUC) of 0.80 (95 %CI 0.76-0.85) in our training cohort and 0.78 (95 %CI 0.70-0.86) in our validation cohort (n = 126). Overall, the BAND score had a significantly higher AUC value than the widely validated THRIVE score and the THRIVE-EVT calculation (p = 0.001 and 0.029, respectively). Among patients with high BAND scores (7 or higher), 88.2 % had poor outcomes. CONCLUSION: The BAND score is a simple tool to predict poor outcomes despite successful recanalization. Future studies are needed to confirm the BAND score's external validity.

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.

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.

Multi-Residency Implementation of an Online Movement Disorders Curriculum Based on Real Patient Videos.

Background: In-person didactic education in residency has numerous challenges including inconsistent availability of faculty and residents, limited engagement potential, and non-congruity with clinical exposure. Methods: An online curriculum in movement disorders was implemented across nine neurology residency programs (six intervention, three control), with the objective to determine feasibility, acceptability, and knowledge growth from the curriculum. Residents in the intervention group completed ten modules and a survey. All groups completed pre-, immediate post-, and delayed post-tests. Results: Eighty-six of 138 eligible housestaff (62.3%) in the intervention group completed some modules and 74 completed at least half of modules. Seventy-four, 49, and 30 residents completed the pre-, immediate post-, and delayed post-tests respectively. Twenty-five of 42 eligible control residents (59.5%) completed at least one test. Mean pre-test scores were not significantly different between groups (6.33 vs. 6.92, p = 0.18); the intervention group had significantly higher scores on immediate post- (8.00 vs. 6.79, p = 0.001) and delayed post-tests (7.92 vs. 6.92, p = 0.01). Residents liked having a framework for movement disorders, appreciated the interactivity, and wanted more modules. Residents completed the curriculum over variable periods of time (1-174 days), and at different times of day. Discussion: This curriculum was feasible to implement across multiple residency programs. Intervention group residents showed sustained knowledge benefit after participating, and residents took advantage of its flexibility in their patterns of module completion. Similar curricula may help to standardize certain types of clinical learning and exposure across residency programs. Highlights: Interactive online tools for resident didactic learning are valuable to residents. Residents learn from interactive online curricula, find the format engaging, and take advantage of the flexibility of online educational tools. Beginner learners appreciate algorithms that help them to approach a new topic.

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.

Current Status of Dyslipidemia Treatment for Stroke Prevention.

PURPOSE OF REVIEW: Elevated cholesterol is an established risk factor for ischemic stroke. The value of statins for stroke prevention has been clear for more than a decade. RECENT FINDINGS: However, the use of new medication combinations such as ezetimibe or proprotein convertase subtilisin-kexin type 9 inhibitors plus statins is increasing and the value for reducing stroke has been shown for these combination therapies. Recent data also support the strategy of lowering triglycerides for stroke prevention. A modern approach to dyslipidemia treatment and its relation to stroke prevention is summarized in this paper.

Management of acute ischemic stroke.

Stroke is the leading cause of long term disability in developed countries and one of the top causes of mortality worldwide. The past decade has seen substantial advances in the diagnostic and treatment options available to minimize the impact of acute ischemic stroke. The key first step in stroke care is early identification of patients with stroke and triage to centers capable of delivering the appropriate treatment, as fast as possible. Here, we review the data supporting pre-hospital and emergency stroke care, including use of emergency medical services protocols for identification of patients with stroke, intravenous thrombolysis in acute ischemic stroke including updates to recommended patient eligibility criteria and treatment time windows, and advanced imaging techniques with automated interpretation to identify patients with large areas of brain at risk but without large completed infarcts who are likely to benefit from endovascular thrombectomy in extended time windows from symptom onset. We also review protocols for management of patient physiologic parameters to minimize infarct volumes and recent updates in secondary prevention recommendations including short term use of dual antiplatelet therapy to prevent recurrent stroke in the high risk period immediately after stroke. Finally, we discuss emerging therapies and questions for future research.

BIIB093 (IV glibenclamide): an investigational compound for the prevention and treatment of severe cerebral edema.

Introduction: Brain swelling due to edema formation is a major cause of neurological deterioration and death in patients with large hemispheric infarction (LHI) and severe traumatic brain injury (TBI), especially contusion-TBI. Preclinical studies have shown that SUR1-TRPM4 channels play a critical role in edema formation and brain swelling in LHI and TBI. Glibenclamide, a sulfonylurea drug and potent inhibitor of SUR1-TRPM4, was reformulated for intravenous injection, known as BIIB093.Areas covered: We discuss the findings from Phase 2 clinical trials of BIIB093 in patients with LHI (GAMES-Pilot and GAMES-RP) and from a small Phase 2 clinical trial in patients with TBI. For the GAMES trials, we review data on objective biological variables, adjudicated edema-related endpoints, functional outcomes, and mortality which, despite missing the primary endpoint, supported the initiation of a Phase 3 trial in LHI (CHARM). For the TBI trial, we review data on MRI measures of edema and the initiation of a Phase 2 trial in contusion-TBI (ASTRAL).Expert opinion: Emerging clinical data show that BIIB093 has the potential to transform our management of patients with LHI, contusion-TBI and other conditions in which swelling leads to neurological deterioration and death.

Beyond the first pass: revascularization remains critical in stroke thrombectomy.

BACKGROUND: The first pass effect has been recently reported as a predictor of good clinical outcome after stroke thrombectomy. We evaluate the first pass effect on outcome and the influence of revascularization in these and other patients. METHODS: We performed a retrospective analysis of a prospectively maintained database on anterior cerebral circulation stroke thrombectomy cases from April 2012 to April 2018. Data compiled included patient demographics, presenting National Institutes of Health Stroke Scale score, vessel occlusion site, thrombectomy procedural details, and 90 day modified Rankin Scale scores. RESULTS: 205 patients were included. The numbers of patients who underwent one, two, three, four, five, and six passes were 69, 70, 55, 9, 1, and 1, respectively. Successful revascularization was achieved in 87%, 83%, and 64% of patients in the one, two, and 3 or more passes groups, respectively (p=0.002). Good functional outcome was inversely correlated with number of passes when comparing the one, two, and three or more passes groups (54%, 43%, 29%; P=0.014). In patients with full revascularization, there was no significant difference in good functional outcomes between the one, two, and three or more passes groups (64%, 65%, 50%; P=0.432). Number of passes was not an independent negative predictor of good clinical outcome (OR 1.66, 95% CI 0.82 to 3.39; P=0.165). CONCLUSIONS: First pass thrombectomy patients have better functional outcomes compared with beyond-first pass patients. This effect is related at least in part to a higher rate of revascularization in one pass patients. Revascularization beyond the first pass should continue to be the goal of stroke thrombectomy.

Carotid webs and ischemic stroke: Experiences in a comprehensive stroke center.

BACKGROUND AND PURPOSE: Carotid webs are intraluminal filling defects at the carotid bulb which are considered rare, though possibly underappreciated entities with recent studies demonstrating a likely casual association with ischemic stroke. The purpose of the study is to describe our recent experience with clinical and imaging manifestations of carotid webs. MATERIALS AND METHODS: A retrospective review of CTA neck studies in all adult patients presenting to our institution during the 19-month study interval was performed to determine the presence of carotid webs. Subsequent chart review of these patients with webs was performed to assess their clinical history and to obtain demographic detail. RESULTS: A total of 14 patients were identified with carotid webs in the study population. The mean age of patients with webs was 42.1 years (range: 28-54), consisting mostly of African Americans (86%) and females (64%). Ten (71%) of web patients had a history of ischemic stroke, each ipsilateral to the side of web, and at least four of these patients had recurrent ischemic stroke. CONCLUSION: We provide one of the largest sample sizes of webs gathered in a single study. Given its association with ischemic stroke, carotid webs should be assessed for in all patients presenting with ischemic stroke, especially younger African Americans.

Smoking and Risk of Ischemic Stroke in Young Men.

BACKGROUND AND PURPOSE: There is a strong dose-response relationship between smoking and risk of ischemic stroke in young women, but there are few data examining this association in young men. We examined the dose-response relationship between the quantity of cigarettes smoked and the odds of developing an ischemic stroke in men under age 50 years. METHODS: The Stroke Prevention in Young Men Study is a population-based case-control study of risk factors for ischemic stroke in men ages 15 to 49 years. The χ2 test was used to test categorical comparisons. Logistic regression models were used to calculate the odds ratio for ischemic stroke occurrence comparing current and former smokers to never smokers. In the first model, we adjusted solely for age. In the second model, we adjusted for potential confounding factors, including age, race, education, hypertension, myocardial infarction, angina, diabetes mellitus, and body mass index. RESULTS: The study population consisted of 615 cases and 530 controls. The odds ratio for the current smoking group compared with never smokers was 1.88. Furthermore, when the current smoking group was stratified by number of cigarettes smoked, there was a dose-response relationship for the odds ratio, ranging from 1.46 for those smoking <11 cigarettes per day to 5.66 for those smoking 40+ cigarettes per day. CONCLUSIONS: We found a strong dose-response relationship between the number of cigarettes smoked daily and ischemic stroke among young men. Although complete smoking cessation is the goal, even smoking fewer cigarettes may reduce the risk of ischemic stroke in young men.

Cocaine Use and Risk of Ischemic Stroke in Young Adults.

BACKGROUND AND PURPOSE: Although case reports have long identified a temporal association between cocaine use and ischemic stroke (IS), few epidemiological studies have examined the association of cocaine use with IS in young adults, by timing, route, and frequency of use. METHODS: A population-based case-control study design with 1090 cases and 1154 controls was used to investigate the relationship of cocaine use and young-onset IS. Stroke cases were between the ages of 15 and 49 years. Logistic regression analysis was used to evaluate the association between cocaine use and IS with and without adjustment for potential confounders. RESULTS: Ever use of cocaine was not associated with stroke with 28% of cases and 26% of controls reporting ever use. In contrast, acute cocaine use in the previous 24 hours was strongly associated with increased risk of stroke (age-sex-race adjusted odds ratio, 6.4; 95% confidence interval, 2.2-18.6). Among acute users, the smoking route had an adjusted odds ratio of 7.9 (95% confidence interval, 1.8-35.0), whereas the inhalation route had an adjusted odds ratio of 3.5 (95% confidence interval, 0.7-16.9). After additional adjustment for current alcohol, smoking use, and hypertension, the odds ratio for acute cocaine use by any route was 5.7 (95% confidence interval, 1.7-19.7). Of the 26 patients with cocaine use within 24 hours of their stroke, 14 reported use within 6 hours of their event. CONCLUSIONS: Our data are consistent with a causal association between acute cocaine use and risk of early-onset IS.

Adherence to Third European Cooperative Acute Stroke Study 3- to 4.5-hour exclusions and association with outcome: data from Get with the Guidelines-Stroke.

BACKGROUND AND PURPOSE: The American Heart Association/American Stroke Association guidelines recommend intravenous tissue-type plasminogen activator (tPA) treatment 3 to 4.5 hours from symptom onset according to criteria used in the Third European Cooperative Acute Stroke Study (ECASS III). However, ECASS III excluded certain patient groups in addition to the standard exclusions used for 0 to 3 hours in the United States: age >80 years, history of stroke and diabetes mellitus, oral anticoagulant treatment, and National Institutes of Health Stroke Scale >25. We investigated adherence to these additional exclusion criteria for patients treated 3 to 4.5 hours from onset and their association with outcome. METHODS: We analyzed data from Get With The Guidelines-Stroke on 32 019 patients with ischemic stroke from 1464 hospitals who were treated with tPA ≤4.5 hours from onset from January 2009 to January 2012, excluding patients transferred from another hospital. The percent of patients meeting versus not meeting each exclusion criterion were compared between treatment time windows. RESULTS: Overall, 1544 of 4910 (31.5%) patients treated with tPA >3 to 4.5 hours had at least 1 of the additional exclusions, the most common was age >80 years. With the exception of prior stroke and diabetes mellitus, the percent of tPA-treated patients with each exclusion criterion was significantly lower at >3 to 4.5 hours compared with 0 to 3 hours. For each additional exclusion criterion, there was no increased risk of symptomatic intracranial hemorrhage or worse hospital outcome for patients treated >3 to 4.5 hours compared with 0 to 3 hours, after adjusting for baseline differences. CONCLUSIONS: Patients with ECASS III-specific exclusion criteria for the >3 to 4.5 hours window are frequently treated with tPA. The presence of the additional exclusion criteria was not associated with worse outcomes in the >3 to 4.5 hours window compared with the 0 to 3 hours window.