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Background: Data on systolic blood pressure (SBP) trajectories in the first 24 hours after endovascular thrombectomy (EVT) in acute ischemic stroke are limited. We sought to identify these trajectories and their relationship to outcomes., Methods: We combined individual-level data from 5 studies of patients with acute ischemic stroke who underwent EVT and had individual blood pressure values after the end of the procedure. We used group-based trajectory analysis to identify the number and shape of SBP trajectories post-EVT. We used mixed effects regression models to identify associations between trajectory groups and outcomes adjusting for potential confounders and reported the respective adjusted odds ratios (aORs) and common odds ratios., Results: There were 2640 total patients with acute ischemic stroke included in the analysis. The most parsimonious model identified 4 distinct SBP trajectories, that is, general directional patterns after repeated SBP measurements: high, moderate-high, moderate, and low. Patients in the higher blood pressure trajectory groups were older, had a higher prevalence of vascular risk factors, presented with more severe stroke syndromes, and were less likely to achieve successful recanalization after the EVT. In the adjusted analyses, only patients in the high-SBP trajectory were found to have significantly higher odds of early neurological deterioration (aOR, 1.84 [95% CI, 1.20-2.82]), intracranial hemorrhage (aOR, 1.84 [95% CI, 1.31-2.59]), mortality (aOR, 1.75 [95% CI, 1.21-2.53), death or disability (aOR, 1.63 [95% CI, 1.15-2.31]), and worse functional outcomes (adjusted common odds ratio,1.92 [95% CI, 1.47-2.50])., Conclusions: Patients follow distinct SBP trajectories in the first 24 hours after an EVT. Persistently elevated SBP after the procedure is associated with unfavorable short-term and long-term outcomes., Competing Interests: Disclosures A.H. Katsanos serves as the PI for the Blood Pressure Management in Stroke Following Endovascular Treatment trial. The other authors report no conflicts.

Introduction: Data on the association between blood pressure variability (BPV) after endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) and outcomes are limited. We sought to identify whether BPV within the first 24 hours post EVT was associated with key stroke outcomes., Methods: We combined individual patient-data from five studies among AIS-patients who underwent EVT, that provided individual BP measurements after the end of the procedure. BPV was estimated as either systolic-BP (SBP) standard deviation (SD) or coefficient of variation (CV) over 24 h post-EVT. We used a logistic mixed-effects model to estimate the association [expressed as adjusted odds ratios (aOR)] between tertiles of BPV and outcomes of 90-day mortality, 90-day death or disability [modified Rankin Scale-score (mRS) > 2], 90-day functional impairment (⩾1-point increase across all mRS-scores), and symptomatic intracranial hemorrhage (sICH), adjusting for age, sex, stroke severity, co-morbidities, pretreatment with intravenous thrombolysis, successful recanalization, and mean SBP and diastolic-BP levels within the first 24 hours post EVT., Results: There were 2640 AIS-patients included in the analysis. The highest tertile of SBP-SD was associated with higher 90-day mortality (aOR:1.44;95% CI:1.08-1.92), 90-day death or disability (aOR:1.49;95% CI:1.18-1.89), and 90-day functional impairment (adjusted common OR:1.42;95% CI:1.18-1.72), but not with sICH (aOR:1.22;95% CI:0.76-1.98). Similarly, the highest tertile of SBP-CV was associated with higher 90-day mortality (aOR:1.33;95% CI:1.01-1.74), 90-day death or disability (aOR:1.50;95% CI:1.19-1.89), and 90-day functional impairment (adjusted common OR:1.38;95% CI:1.15-1.65), but not with sICH (aOR:1.33;95% CI:0.83-2.14)., Conclusions: BPV after EVT appears to be associated with higher mortality and disability, independently of mean BP levels within the first 24 h post EVT. BPV in the first 24 h may be a novel target to improve outcomes after EVT for AIS., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Katsanos serves as the PI for the Blood Pressure Management in Stroke Following Endovascular Treatment (DETECT) trial.

Background: Endovascular thrombectomy (EVT) is efficacious for appropriately selected patients with large vessel occlusions (LVO) up to 24 hours from symptom onset. There is limited information on outcomes of nonagenarians, selected with computed tomography perfusion (CTP) imaging., Methods: We retrospectively analyzed data from a large academic hospital between December 2017 and October 2019. Patients receiving EVT for anterior circulation LVO were stratified into nonagenarian (≥90 years) and younger (<90 years) groups. We performed propensity score matching on 18 covariates. In the matched cohort we compared: primary outcome of inpatient mortality and secondary outcomes of successful reperfusion (TICI ≥2B), symptomatic intracranial hemorrhage (sICH), and functional independence. Subgroup analysis compared CTP predicted core volumes in nonagenarians with outcomes., Results: Overall, 214 consecutive patients (26 nonagenarians, 188 younger) underwent EVT. Nonagenarians were aged 92.8±2.9 years and younger patients were 74.5±13.5 years. Mortality rate was significantly greater in nonagenarians compared with younger patients (43.5% vs 10.4%, OR 9.33, 95% CI 2.88 to 47.97, P<0.0001) and a greater proportion of nonagenarians developed sICH (13.0% vs 3.0%, OR 6.00, 95% CI 1.34 to 55.20, P=0.02). There were no significant differences for successful reperfusion (P=1.00) or functional independence (P=0.75). Nonagenarians selected with smaller ischemic core volumes had decreased mortality rates (P=0.045)., Conclusions: Nonagenarians were noted to have greater mortality and sICH rates following EVT compared with matched younger patients, which may be ameliorated by selecting patients with smaller CTP core volumes. Nonagenarians undergoing EVT had similar rates of successful reperfusion and functional independence compared with the younger cohort., Competing Interests: Competing interests: RC is a member of the iSchemaView advisory board. All other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: To explore the association between blood pressure (BP) levels after endovascular thrombectomy (EVT) and the clinical outcomes of patients with acute ischemic stroke (AIS) patients with large vessel occlusion (LVO)., Methods: A study was eligible if it enrolled patients with AIS >18 years of age with an LVO treated with either successful or unsuccessful EVT and provided either individual or mean 24-hour systolic BP values after the end of the EVT procedure. Individual patient data from all studies were analyzed with a generalized linear mixed-effects model., Results: A total of 5,874 patients (mean age 69 ± 14 years; 50% women; median NIH Stroke Scale score on admission 16) from 7 published studies were included. Increasing mean systolic BP levels per 10 mm Hg during the first 24 hours after the end of the EVT were associated with a lower odds of functional improvement (unadjusted common odds ratio [OR] 0.82, 95% confidence interval [CI] 0.80-0.85; adjusted common OR 0.88, 95% CI 0.84-0.93) and modified Rankin Scale score ≤2 (unadjusted OR 0.82, 95% CI 0.79-0.85; adjusted OR 0.87, 95% CI 0.82-0.93) and a higher odds of all-cause mortality (unadjusted OR 1.18, 95% CI 1.13-1.24; adjusted OR 1.15, 95% CI 1.06-1.23) at 3 months. Higher 24-hour mean systolic BP levels were also associated with an increased likelihood of early neurologic deterioration (unadjusted OR 1.14, 95% CI 1.07-1.21; adjusted OR 1.14, 95% CI 1.03-1.24) and a higher odds of symptomatic intracranial hemorrhage (unadjusted OR 1.20, 95% CI 1.09-1.29; adjusted OR 1.20, 95% CI 1.03-1.38) after EVT., Discussion: Increased mean systolic BP levels in the first 24 hours after EVT are independently associated with a higher odds of symptomatic intracranial hemorrhage, early neurologic deterioration, 3-month mortality, and worse 3-month functional outcomes., (© 2021 American Academy of Neurology.)

Objective: To assess the utility of IV thrombolysis (IVT) treatment in patients with acute ischemic stroke (AIS) with unclear symptom onset time or outside the 4.5-hour time window selected by advanced neuroimaging., Methods: We performed random-effects meta-analyses on the unadjusted and adjusted for potential confounders associations of IVT (alteplase 0.9 mg/kg) with the following outcomes: 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] scores 0-1), 3-month functional independence (FI; mRS scores 0-2), 3-month mortality, 3-month functional improvement (assessed with ordinal analysis on the mRS scores), symptomatic intracranial hemorrhage (sICH), and complete recanalization (CR)., Results: We identified 4 eligible randomized clinical trials (859 total patients). In unadjusted analyses, IVT was associated with a higher likelihood of 3-month FFO (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.12-1.96), FI (OR 1.42, 95% CI 1.07-1.90), sICH (OR 5.28, 95% CI 1.35-20.68), and CR (OR 3.29, 95% CI 1.90-5.69), with no significant difference in the odds of all-cause mortality risk at 3 months (OR 1.75, 95% CI 0.93-3.29). In the adjusted analyses, IVT was also associated with higher odds of 3-month FFO (adjusted OR [OR adj ] 1.62, 95% CI 1.20-2.20), functional improvement (OR adj 1.42, 95% CI 1.11-1.81), and sICH (OR adj 6.22, 95% CI 1.37-28.26). There was no association between IVT and FI (OR adj 1.61, 95% CI 0.94-2.75) or all-cause mortality (OR adj 1.75, 95% CI 0.93-3.29) at 3 months. No evidence of heterogeneity was evident in any of the analyses ( I 2 = 0)., Conclusion: IVT in patients with AIS with unknown symptom onset time or elapsed time from symptom onset >4.5 hours selected with advanced neuroimaging results in a higher likelihood of CR and functional improvement at 3 months despite the increased risk of sICH., (© 2019 American Academy of Neurology.)

Objective: Conflicting data exist on the safety and efficacy of IV thrombolysis (IVT) in patients with acute ischemic stroke (AIS) receiving dual antiplatelet pretreatment (DAPP). The aim of the present systematic review and meta-analysis is to assess the safety and outcome of DAPP history among patients with AIS treated with IVT., Methods: We performed a comprehensive literature review to identify studies that investigated the safety and efficacy of DAPP among patients with AIS treated with IVT., Results: We identified 9 studies comprising 66,675 patients. In unadjusted analyses, DAPP was associated with a higher likelihood of pooled symptomatic intracranial hemorrhage (sICH; odds ratio [OR] 2.26; 95% confidence interval [CI] 1.39-3.67) and 3-month mortality (OR 1.47; 95% CI 1.25-1.73). DAPP was also related to higher odds of sICH according to Safe Implementation of Treatments in Stroke Monitoring Study (OR 2.71; 95% CI 2.05-3.59), European Cooperative Acute Stroke Study II (OR 2.23; 95% CI 1.46-3.40), and National Institute of Neurological Disorders and Stroke (OR 1.59, 95% CI 1.38-1.83) definitions. There was no association between DAPP and 3-month favorable functional outcome (FFO, modified Rankin Scale [mRS] score 0-1) and 3-month functional independence (FI; mRS score 0-2). In adjusted analyses, history of DAPP was not associated with pooled sICH (OR 2.03; 95% CI 0.75-5.52), 3-month mortality (OR 1.11; 95% CI 0.87-1.40), 3-month FFO (OR 0.92; 95% CI 0.77-1.09), and 3-month FI (OR 1.01; 95% CI 0.89-1.15)., Conclusions: After adjustment for potential confounders, DAPP appears not to be associated with higher risk of adverse outcomes in patients with AIS treated with IVT., (© 2020 American Academy of Neurology.)

Background Recent randomized controlled clinical trials have provided solid evidence that mechanical thrombectomy (MT) coupled with best medical therapy (BMT) improve functional outcomes of acute ischemic stroke patients with large vessel occlusion compared with BMT alone. However, they provided inconclusive evidence on the benefit of MT on mortality. Methods and Results We evaluated the association of MT+BMT compared with BMT with the risk of 3-month mortality using aggregate data from all available randomized controlled clinical trials. We also sought to identify potential predictors on the mortality risk and performed univariate meta-regression analyses. Our literature search identified 11 eligible randomized controlled clinical trials, including a total of 2460 patients. The pooled rates of 3-month mortality were 15% (95% CI:12%-19%) and 19% (95% CI:16%-23%), respectively, in the MT+BMT and BMT groups. In the overall analysis MT+BMT was associated with a significantly lower risk for 3-month mortality compared with BMT (risk ratio=0.83, 95% CI:0.69-0.99; P =0.04), without heterogeneity across included studies (I 2 =3%, P for Cochran Q=0.41). No evidence of publication bias was present in funnel plot inspection and Egger statistical test ( P =0.762). In meta-regression analyses no moderating effect on the aforementioned association was detected with patient age ( P =0.254), sex ( P =0.702), admission systolic blood pressure ( P =0.601), admission glucose ( P =0.277), onset-to-groin puncture time ( P =0.985), administration of intravenous alteplase before MT ( P =0.804), MT under general anesthesia ( P =0.735), and successful reperfusion following MT ( P =0.663). Conclusions Our meta-analysis provides evidence that MT+BMT reduces the risk of 3-month mortality compared with BMT alone. This association appears not to be moderated by individual patient or procedural characteristics.

Objective: The substantial clinical improvement in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT), combined with the poor response of proximal intracranial occlusions to intravenous thrombolysis (IVT), led to questions regarding the utility of bridging therapy (BT; IVT followed by MT) compared to direct mechanical thrombectomy (dMT) for AIS patients with large vessel occlusion (LVO)., Methods: We aimed to investigate the comparative safety and efficacy of BT and dMT in AIS patients. We included all observational studies and post hoc analyses from randomized controlled clinical trials that provided data on the outcomes of AIS patients with LVO stratified by IVT treatment status prior to MT., Results: We identified 38 eligible observational studies (11,798 LVO patients, mean age = 68 years, 56% treated with BT). In unadjusted analyses, BT was associated with a higher likelihood of 3-month functional independence (odds ratio [OR] = 1.52, 95% confidence interval [CI] = 1.32-1.76), 3-month functional improvement (common OR [cOR] for 1-point decrease in modified Rankin Scale score = 1.52, 95% CI = 1.18-1.97), early neurological improvement (OR = 1.21, 95% CI = 1.83-1.76), successful recanalization (OR = 1.22, 95% CI = 1.02-1.46), and successful recanalization with ≤2 device passes (OR = 2.28, 95% CI = 1.43-3.64) compared to dMT. BT was also related to a lower likelihood of 3-month mortality (OR = 0.64, 95% CI = 0.57-0.73). In the adjusted analyses, BT was independently associated with a higher likelihood of 3-month functional independence (adjusted OR = 1.55, 95% CI = 1.26-1.91) and lower odds of 3-month mortality (adjusted OR = 0.80, 95% CI = 0.66-0.97) compared to dMT. The two groups did not differ in functional improvement (adjusted cOR = 1.24, 95% CI = 0.89-1.74) or symptomatic intracranial hemorrhage (adjusted OR = 0.87, 95% CI = 0.61-1.25)., Interpretation: BT appears to be associated with improved functional independence without evidence for safety concerns, compared to dMT, for AIS patients with LVO. ANN NEUROL 2019;86:395-406., (© 2019 American Neurological Association.)

Introduction: Debate continues about the optimal anesthetic management for patients undergoing endovascular treatment (ET) of acute ischemic stroke due to emergent large vessel occlusion., Objective: To compare, using current evidence, the clinical outcomes and procedural characteristics among patients undergoing general anesthesia (GA) and local or monitored anesthesia (non-GA)., Methods: We performed a systematic review and meta-analysis of all available studies that involved the use of stent retrievers for ET (stentriever group). Additionally, we included studies that were published in 2015 and later, and compared the clinical outcomes among the studies using stentrievers or no stentrievers (pre-stentriever group). Outcome variables included functional independence (FI; modified Rankin Scale scores of 0-2), symptomatic hemorrhage, mortality, procedure duration, and vascular and respiratory complications. We calculated pooled odds ratios and 95% CIs using random-effects models., Results: Sixteen studies (three randomized controlled clinical trials (RCTs) and 13 non-randomized studies) were identified comprising 5836 patients. Although non-GA was associated with higher odds of 3-month FI (OR=1.57; 95% CI 1.17 to 2.10; P=0.003) and lower odds of 3-month mortality (OR=0.62; 95% CI 0.47 to 0.82; P=0.0006, substantial heterogeneity was noted across included trials. Sensitivity analyses of RCTs showed that non-GA was inversely associated with FI (OR=0.55; 95% CI 0.34 to 0.89; P=0.01; I 2 =15%), while no association was noted with mortality (OR=1.36; 95% CI 0.79 to 2.34; P=0.27; I 2 =0%)., Conclusion: Our updated meta-analysis demonstrates favorable results with non-GA, probably owing to inclusion of non-randomized studies. Recent single-center RCTs indicate that GA is associated with higher odds of FI at 3 months, while other outcomes are similar between the two groups., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: In this multicenter study, we sought to evaluate comparative safety and efficacy of combined IV thrombolysis (IVT) and mechanical thrombectomy (MT) vs direct MT in emergent large vessel occlusion (ELVO) patients., Methods: Consecutive ELVO patients treated with MT at 6 high-volume endovascular centers were evaluated. Standard safety and efficacy outcomes (successful reperfusion [modified Thrombolysis in Cerebral Infarction IIb/III], functional independence [FI] [modified Rankin Scale (mRS) score of 0-2 at 3 months], favorable functional outcome [mRS of 0-1 at 3 months], functional improvement [mRS shift by 1-point decrease in mRS score]) were compared between patients who underwent combined IVT and MT vs MT alone. Additional propensity score-matched analyses were performed., Results: A total of 292 and 277 patients were treated with combination therapy and direct MT, respectively. The combination therapy group had greater functional improvement ( p = 0.037) at 3 months. After propensity score matching, 104 patients in the direct MT group were matched to 208 patients in the combination therapy group. IVT pretreatment was independently ( p < 0.05) associated with higher odds of FI (odds ratio [OR] 1.75; 95% confidence interval [CI] 1.02-2.99) and functional improvement (common OR 1.64; 95% CI 1.05-2.56). Combination therapy was independently ( p < 0.05) related to lower likelihood of 3-month mortality (0.50; 95% CI 0.26-0.96)., Conclusions: This observational study provides preliminary evidence that IVT pretreatment may improve outcomes in ELVO patients treated with MT. The question of the potential effect of IVT on ELVO patients treated with MT should be addressed with a randomized controlled trial., Classification of Evidence: This study provides Class III evidence that for stroke patients with emergent large vessel occlusion, combined IVT and MT is superior to direct MT in improving functional outcomes., (© 2018 American Academy of Neurology.)

Objective: The total number of citations of a research article can be used to determine its impact on the scientific community. We aimed to identify the top-100 articles published on ischemic stroke and evaluate their characteristics., Methods: Based on the database of Journal Citation Reports, 934 journals were selected that published original ischemic stroke articles. We used Web of Science citation search tool to identify top-100 citation classics, i.e., articles with more than 400 citations, in the field of ischemic stroke. All original articles were evaluated for publication year, journal category, journal and its impact factor, number of total and annual citations, research topic, publishing country, and institutional affiliation., Results: The top-100 citation classics in ischemic stroke were published from 1970 to 2015, with the decade of 1990-1999 contributing 47 articles of historical significance. Median of total citations and annual citations in our analysis were 625.0 (interquartile range [IQR] 851.3-494.5) and 35.7 (IQR 79.9-25.9), respectively. The majority of the articles originated from the United States (n = 57), focused over the medical management (n = 26), and were published in the New England Journal of Medicine or Stroke (n = 25 each) journals. The median impact factor for the journals that published top-100 ischemic stroke citation classics was 9.11 (IQR 21.49-6.11)., Conclusions: Our list of top-100 citation classics specific to ischemic stroke provide a detailed insight into academic achievements, historical perspective and serves as a guide for the scientific progress in stroke., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background and Purpose: Pharmacokinetic and prior studies on thienopyridine and proton pump inhibitors (PPI) coadministration provide conflicting data for cardiovascular outcomes, whereas there is no established evidence on the association of concomitant use of PPI and thienopyridines with adverse cerebrovascular outcomes., Methods: We conducted a systematic review and meta-analysis of randomized controlled trials and cohort studies from inception to July 2017, reporting following outcomes among patients treated with thienopyridine and PPI versus thienopyridine alone (1) ischemic stroke, (2) combined ischemic or hemorrhagic stroke, (3) composite outcome of stroke, myocardial infarction (MI), and cardiovascular death, (4) MI, (5) all-cause mortality, and (6) major or minor bleeding events. After the unadjusted analyses of risk ratios, we performed additional analyses of studies reporting hazard ratios adjusted for potential confounders., Results: We identified 22 studies (12 randomized controlled trials and 10 cohort studies) comprising 131 714 patients. Concomitant use of PPI with thienopyridines was associated with increased risk of ischemic stroke (risk ratio, 1.74; 95% confidence interval [CI], 1.41-2.16; P <0.001), composite stroke/MI/cardiovascular death (risk ratio, 1.14; 95% CI, 1.01-1.29; P =0.04), and MI (risk ratio, 1.19; 95% CI, 1.00-1.40; P =0.05). Likewise, in adjusted analyses concomitant use of PPI with thienopyridines was again associated with increased risk of stroke (hazard ratios adjusted, 1.30; 95% CI, 1.04-1.61; P =0.02), composite stroke/MI/cardiovascular death (hazard ratios adjusted, 1.23; 95% CI, 1.03-1.47; P =0.02), but not with MI (hazard ratios adjusted, 1.19; 95% CI, 0.93-1.52; P =0.16)., Conclusions: Co-prescription of PPI and thienopyridines increases the risk of incident ischemic strokes and composite stroke/MI/cardiovascular death. Our findings corroborate the current guidelines for PPI deprescription and pharmacovigilance, especially in patients treated with thienopyridines., (© 2018 American Heart Association, Inc.)