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Background: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations., Methods: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization., Results: A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis., Conclusions: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Trials of the efficacy and safety of endovascular thrombectomy in patients with large ischemic strokes have been carried out in limited populations., Methods: We performed a prospective, randomized, open-label, adaptive, international trial involving patients with stroke due to occlusion of the internal carotid artery or the first segment of the middle cerebral artery to assess endovascular thrombectomy within 24 hours after onset. Patients had a large ischemic-core volume, defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower scores indicating larger infarction) or a core volume of at least 50 ml on computed tomography perfusion or diffusion-weighted magnetic resonance imaging. Patients were assigned in a 1:1 ratio to endovascular thrombectomy plus medical care or to medical care alone. The primary outcome was the modified Rankin scale score at 90 days (range, 0 to 6, with higher scores indicating greater disability). Functional independence was a secondary outcome., Results: The trial was stopped early for efficacy; 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group. The generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (95% confidence interval [CI], 1.20 to 1.89; P<0.001). A total of 20% of the patients in the thrombectomy group and 7% in the medical-care group had functional independence (relative risk, 2.97; 95% CI, 1.60 to 5.51). Mortality was similar in the two groups. In the thrombectomy group, arterial access-site complications occurred in 5 patients, dissection in 10, cerebral-vessel perforation in 7, and transient vasospasm in 11. Symptomatic intracranial hemorrhage occurred in 1 patient in the thrombectomy group and in 2 in the medical-care group., Conclusions: Among patients with large ischemic strokes, endovascular thrombectomy resulted in better functional outcomes than medical care but was associated with vascular complications. Cerebral hemorrhages were infrequent in both groups. (Funded by Stryker Neurovascular; SELECT2 ClinicalTrials.gov number, NCT03876457.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke., Methods: In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0·9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants., Findings: Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7·3%, 95% CI -16·6 to 2·1, lower limit of one-sided 95% CI -15·1%, crossing the non-inferiority margin of -12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy (risk difference -1·0%, 95% CI -4·8 to 2·7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [91%] of 201 vs 199 [96%] of 207, risk difference -5·1%, 95% CI -10·2 to 0·0, p=0·047)., Interpretation: Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients., Funding: Medtronic and University Hospital Bern., Competing Interests: Declaration of interests UF reports financial support for the present study from Medtronic; research grants from Medtronic BEYOND SWIFT registry, the Swiss National Science Foundation, and the Swiss Heart Foundation; consulting fees from Medtronic, Stryker, and CSL Behring (fees paid to institution); has membership of a data safety monitoring board for the IN EXTREMIS trial and the TITAN trial; was on the advisory board for Portola (Alexion; fees paid to institution); and is Vice President of the Swiss Neurological Society. JK reports financial support from Medtronic for the BEYOND SWIFT registry (fees paid to institution); and research grants from the Swiss National Science Foundation supporting the TECNO trial (fees paid to institution), Swiss Academy of Medical Sciences supporting MRI research (fees paid to institution), and Swiss Heart Foundation supporting cardiac MRI in the aetiological work-up of stroke patients (fees paid to institution). CC reports consulting fees from Medtronic. PMo reports research funding (fees paid to institution) from the Swiss National Science Foundation, the Swiss Heart Foundation, and Medtronic. GM reports consulting fees from Stryker Neurovascular; and was paid for lectures for Medtronic and Microvention Europe. IS reports consulting fees from Sanofi Synthé-Labo, Servier, Boheringer Ingelheim, AstraZeneca, Novonordisk, and Medtronic; and payment or honoraria from Sanofi Synthé-Labo, Medtronic, Boheringer Ingelheim, AstraZeneca, and BMS—Pfizer. ON reports funding from a Stryker Research grant; and payment or honoraria for lectures for Phenox and Stryker. MR reports consulting fees from Medtronic, Stryker, Cerenovus, Philips, and Apta Targets; payment or honoraria from Ischemia View; participates on a data safety monitoring board or advisory board of Sensome; and has stock or stock options in Anaconda Biomed, CVAid, and Methinks. EC reports grants from the Swiss Heart Foundation and Swiss National Science Foundation, not related to the present study. ARL reports grants from the University of Zurich, the LOOP Zurich, and P&K Pühringer Foundation; consulting fees from Bayer; and a lecture honorarium from Moleac Pte, Singapore. WP reports grants from the German Research Foundation, LOEWE (research funding of the federal state of Hesse); royalties or licenses from the Stroke Team Training (Laerdal Medical); payment or honoraria from Laerdal Medical, Alexion, Pfizer—BMS, and Stryker Neurovascular; and support for attending meetings or travel from Laerdal Medical, Alexion, Pfizer—BMS, and Stryker Neurovascular. MA reports honoraria for lectures from AstraZeneca, Bayer, Covidien, Medtronic, and Sanofi; and participates on scientific advisory boards of Amgen, Bayer, BMS, Daiichi Sankyo, Medtronic, and Pfizer. AHS reports being a coinvestigator for the US National Institutes of Health (1R01EB030092-01); is mentor for the Carol W Harvey Chair of Research and Sharon Epperson Chair of Research at the Brain Aneurysm Foundation; receipt of consulting fees from Amnis Therapeutics, Apellis Pharmaceuticals, Boston Scientific, Canon Medical Systems USA, Cardinal Health 200, Cerebrotech Medical Systems, Cerenovus, Cerevatech Medical, Cordis, Corindus, Endostream Medical, Imperative Care, InspireMD, Integra, IRRAS AB, Medtronic, MicroVention, Minnetronix Neuro, Peijia Medical, Penumbra, Q’Apel Medical, Rapid Medical, Serenity Medical, Silk Road Medical, StimMed, Stryker Neurovascular, Three Rivers Medical, VasSol, and Viz.ai; is Secretary of the Board of the Society of NeuroInterventional Surgery 2020–2021 (unpaid); is Chair of the Cerebrovascular Section of the AANS/CNS 2020–2021 (unpaid); has stock or stock options in Adona Medical, Amnis Therapeutics, Bend IT Technologies, BlinkTBI, Cerebrotech Medical Systems, Cerevatech Medical, Cognition Medical, CVAID, E8, Endostream Medical, Galaxy Therapeutics, Imperative Care, InspireMD, Instylla, International Medical Distribution Partners, Launch NY, NeuroRadial Technologies, NeuroTechnology Investors, Neurovascular Diagnostics, Peijia Medical, PerFlow Medical, Q’Apel Medical, QAS.ai, Radical Catheter Technologies, Rebound Therapeutics (purchased 2019 by Integra Lifesciences), Rist Neurovascular, (purchased 2020 by Medtronic), Sense Diagnostics, Serenity Medical, Silk Road Medical, Sim & Cure, SongBird Therapy, Spinnaker Medical, StimMed, Synchron, Three Rivers Medical, Truvic Medical, Tulavi Therapeutics, Vastrax, VICIS, and Viseon; and other financial or non-financial interests: national principal investigator or steering committees for Cerenovus EXCELLENT and ARISE II Trial; Medtronic SWIFT PRIME, VANTAGE, EMBOLISE and SWIFT DIRECT Trials; MicroVention FRED Trial and CONFIDENCE Study; MUSC POSITIVE Trial; Penumbra 3D Separator Trial, COMPASS Trial, INVEST Trial, MIVI neuroscience EVAQ Trial; Rapid Medical SUCCESS Trial; and InspireMD C-GUARDIANS IDE Pivotal Trial. MTF reports research grants from Medtronic, Siemens, Genentech, Idorsia, and Vesalio; consulting fees from Genentech, Balt USA, CereNovus, and Oculus Imaging; and participates on a data safety monitoring board or advisory board for Balt USA, Jacobs Institute, and Imperative Care. MW reports a grant from Stryker Neurovascular; consulting fees from Stryker Neurovascular; payment or honoraria from Stryker Neurovascular and Bracco Imaging; is board member for the German Society of Neuroradiology (no payments); and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Ab medica, Acandis, Bracco Imaging, Cerenovus, Kaneka Pharmaceuticals, Medtronic, Mentice, Phenox, and Stryker Neurovascular (support to institution). PMa reports grants from the Swiss National Science Foundation; consulting fees from Medtronic and Stryker; payment or honoraria from Medtronic and Stryker; and participated on a data safety monitoring board or advisory board of MicroVention. H-CD reports honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from Abbott, BMS, Boehringer Ingelheim, Daiichi-Sankyo, Novo-Nordisk, Pfizer, Portola, and WebMD Global; financial support for research projects from Boehringer Ingelheim; received research grants from the German Research Council and German Ministry of Education and Research; serves as Editor of Neurologie up2date, InFo Neurologie & Psychiatrie, Arzneimitteltherapie, and coeditor of Cephalalgia; and is on the editorial board of The Lancet Neurology and Drugs. MM reports payment or honoraria from Boehringer Ingelheim. DSL reports consulting fees from Cerenovus, Genentech, Medtronic, Stryker, and Rapid Medical as imaging core laboratory. JLS reports funding for the present study from Medtronic; consulting fees from Cerenovus; participates on a data safety monitoring board or advisory board for MIVI and Phillips; and has stock or stock options in Rapid Medical. JG reports a Swiss National Funds grant for MRI in stroke. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: There is increasing use of automated computed tomography perfusion (CTP) to aid thrombectomy decision in emergent large vessel occlusion. It is important to understand the performance of these software packages in predicting ischemic core and tissue-at-risk in the real-world setting. The aim of this study was to evaluate whether ischemic core on non-contrast CT (NCCT) and automated CTP correspond and predict infarct extent after thrombectomy for ischemic stroke., Methods: Consecutive patients with acute anterior circulation large vessel occlusion undergoing successful thrombectomy (TICI 2b/3) were studied. All patients had baseline CT, CTP with RAPID post-processing software (RAPID-CTP), and post-thrombectomy 24 h CT. Ischemic cores were assessed by two blinded raters independently using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) on each modality. The interrater agreement for ASPECTS, and correlation between baseline CT-ASPECTS, RAPID-CTP-ASPECTS, and 24h CT-ASPECTS were calculated., Results: A total of 86 patients with a mean age of 70.3 years (SD 16.5) were studied. The median baseline CT-ASPECTS was 9.5 (interquartile range, IQR 8-10), median RAPID-CTP-ASPECTS was 9 (IQR 8-10), and mean RAPID-CTP-ischemic core volume was 14.4 ml (SD 27.9 ml). The mean mismatch volume (difference of Tmax > 6s and cerebral blood flow (CBF) < 30%) was 128.6 ml (SD 126.0 ml). There was substantial correlation between baseline and 24h CT-ASPECTS (r s : 0.62; p < 0.001), but poor correlation between RAPID-CTP-ASPECTS and RAPID-CTP ischemic core volume with 24h NCCT-ASPECTS (r s : 0.21; p = 0.06 and -0.16; p = 0.15 respectively). The positive predictive value of any established infarct for baseline CT-ASPECTS was 81%, while that of RAPID-CTP-ASPECTS was 64%., Conclusion: In this series of successfully revascularized patients, ischemic core as estimated by RAPID-CTP-ASPECTS did not correlate with the baseline CT and tended to depict a larger infarct core than the infarct extent as assessed by 24h CT-ASPECTS.

Background: The time-benefit relationship of endovascular thrombectomy (EVT) according to the size of the core infarct has been incompletely explored in prior studies. We investigated whether established infarct core size on baseline imaging modifies the relationship between onset-to-reperfusion time (OTR) and functional outcomes in patients with acute ischemic stroke treated with EVT., Methods: We analyzed a database containing individual patient data pooled from three prospective Solitaire stent retriever studies. The inclusion criteria were treatment with a Solitaire device and achievement of substantial reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3). Main analyses were performed in patients with baseline Alberta Stroke Program Early CT Scores (ASPECTSs) of 7-10., Results: Among the 305 patients (mean age 67±13 years, 58% women), the proportions of patients in different categories of pretreatment infarct extent were: small (ASPECTS 9-10) 52.0%, moderate (ASPECTS 7-8) 37.1%, and large (ASPECTS 0-6) 7.6%. The mean OTR was 297±95 min. At 3 months, 60.1% of the patients achieved a good outcome. For OTRs of 2-8 hours, the rates of good outcomes at all time points were higher with higher baseline ASPECTS but declined with similar steepness. Both baseline ASPECTS (OR 1.23 (95% CI 1.04 to 1.45)) and OTR (every 30 min delay, OR 0.80 (95% CI 0.73 to 0.88)) were independently associated with a good 3-month outcome. No interaction between OTR and baseline ASPECTS was observed., Conclusions: Although patients with higher baseline ASPECTS are more likely to have good clinical outcomes at all OTR intervals after 2 hours, this benefit consistently declines with time, even in patients with a small infarct core, reinforcing the need to treat all patients as quickly as possible., Competing Interests: Competing interests: MG: served as a consultant to Medtronic for design and conduct of the SWIFT PRIME trial; has also received honoraria from Medtronic/Covidien for speaking and teaching engagements; and was also one of the Principal Investigators for the ESCAPE trial. The ESCAPE trial was partially funded by Covidien through an unrestricted research grant to the University of Calgary. EIL: serves as a scientific consultant to Medtronic; has shareholder/ownership interest with Intratech Medical and Blockade Medical; has received fees from Abbott for carotid training; and has served as an expert witness for Renders Medical/Legal opinion. DL: a consultant to Stryker (modest) and Covidien (modest) and employed by the University of California, which holds a patent on retriever devices for stroke. RJ is a consultant for Medtronic. VMP: is a consultant for Medtronic (PI for SWIFT PRIME trial), Stryker (SC for DAWN trial [DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention]), Penumbra (SC for PROMISE study), and BALT (proctorship of products unrelated to ischemic stroke) and receives research grant from Philips. JG: is a global PI of STAR and SWIFT DIRECT (Medtronic), Consultancy; CEC member of the PROMISE study (Penumbra), Consultancy; and receives SNSF grants for magnetic resonance imaging in stroke. AB: has been a consultant for Covidien and has a licensing agreement with GE. JLS is an employee of the University of California. The University of California Regents receive funding for JLS’s services as a scientific consultant regarding trial design and conduct to Medtronic/Covidien, Stryker, Neuravia, BrainsGate, Pfizer, Squibb, Boehringer Ingelheim (prevention only), ZZ Biotech, and St Jude Medical. JLS has served as an unpaid site investigator in multicenter trials run by Lundbeck for which the University of California Regents received payments on the basis of clinical trial contracts for the number of subjects enrolled. JLS serves as an unpaid consultant to Genentech advising on the design and conduct of the PRISMS trial; neither the University of California nor JLS received any payments for this voluntary service. The University of California has patent rights in retrieval devices for stroke., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Different CT-based protocols are being used in acute ischemic stroke. We aimed to assess the added value of delayed-phase CT angiography (CTA) and CT perfusion (CTP) to a basic protocol using non-contrast computerized tomography (NCCT) with arterial-phase CTA in patient selection for mechanical thrombectomy., Methods: We retrospectively included consecutive acute ischemic stroke patients with a symptomatic intracranial arterial occlusion between January 2015 and November 2016 who underwent NCCT, arterial and delayed-phase CTA, and CTP. These imaging studies were grouped into five protocols: (1) NCCT and arterial-phase CTA; (2) NCCT, arterial-phase CTA, and CTP; (3) NCCT, arterial- and delayed-phase CTA; (4) NCCT, arterial- and delayed-phase CTA, and CTP; and (5) NCCT and delayed-phase CTA. Two interventional neuro-radiologists independently decided on mechanical thrombectomy for each patient based on the protocols. They reached consensus for discrepant decisions. We assessed the raters' confidence level, inter-rater agreement, and compared treatment decisions for the different protocols., Results: We included 73 patients (44% male, mean age 74). The inter-rater agreement was substantial for protocols with three or more modalities (ҡ = 0.613-0.704) and moderate for two-modality protocols (ҡ = 0.506-0.529). The highest agreement and confidence level was achieved for the combination of NCCT, arterial-phase CTA, and CTP. Adding CTP to NCCT and arterial-phase CTA resulted in a 10% increase of recommendations for mechanical thrombectomy and adding delayed-phase CTA resulted in a 4% increase. These management changes did not reach statistical significance (p = 0.07; p = 0.25, respectively)., Conclusion: Adding CTP and/or a delayed-phase CTA to NCCT with arterial-phase CTA improves the decision-maker's confidence level and creates a trend towards a lower threshold for mechanical thrombectomy.

Background: Despite the proven benefit of neurothrombectomy, intracranial hemorrhage (ICH) remains the most serious procedural complication. The aim of this analysis was to identify predictors of different hemorrhage subtypes and evaluate their individual impact on clinical outcome., Methods: Pooled individual patient-level data from three large prospective multicenter studies were analyzed for the incidence of different ICH subtypes, including any ICH, hemorrhagic transformation (HT), parenchymal hematoma (PH), subarachnoid hemorrhage (SAH), and symptomatic intracranial hemorrhage (sICH). All patients (n=389) treated with the Solitaire device were included in the analysis. A multivariate stepwise logistic regression model was used to identify predictors of each hemorrhage subtype., Results: General anesthesia and higher baseline Alberta Stroke Program Early CT score (ASPECTS) were associated with a lower probability of any ICH (OR 0.36, p = 0.003), (OR 0.80, p = 0.032) and HT (OR 0.54, p = 0.023), (OR 0.78, p=0.001), respectively. Longer time from onset to treatment was associated with a higher likelihood of HT (OR 1.08, p = 0.001) and PH (OR 1.11, p = 0.015). Intravenous tissue plasminogen activator (IV-tPA) was also a strong predictor of PH (OR 7.63, p = 0.013). Functional independence at 90 days (modified Rankin Scale (mRS) 0-2) was observed significantly less frequently in all hemorrhage subtypes except SAH. None of the patients who achieved functional independence at 90 days had sICH., Conclusions: General anesthesia and smaller baseline ischemic core are associated with a lower probability of HT whereas IV-tPA and prolonged time to treatment increase the risk of PH after neurothrombectomy., Trial Registration Numbers: SWIFT-NCT01054560; post results, SWIFT PRIME-NCT01657461; post results, STAR-NCT01327989; post results., Competing Interests: Competing interests: All co-authors are consultants for Medtronic Neurovascular., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Performing mechanical thrombectomy (MT) in patients with basilar artery occlusion (BAO) is currently not evidence-based., Objective: To compare patients' outcome, relative merits of achieving recanalization, and predictors of futile recanalization (FR) between BAO and anterior circulation large vessel occlusion (ACLVO) MT., Methods: In the multicenter BEYOND-SWIFT registry (NCT03496064), univariate and multivariate (displayed as adjusted Odds Ratios, aOR and 95% confidence intervals, 95%-CI) outcome comparisons between BAO (N=165) and ACLVO (N=1574) were performed. The primary outcome was favorable outcome at 90 days (modified Rankin Scale, mRS 0-2). Secondary outcome included mortality, symptomatic intracranial hemorrhage (sICH) and FR. The relative merits of achieving successful recanalization between ACLVO and BAO were evaluated with interaction terms., Results: MT in BAO was more often technically effective and equally safe in regards to mortality and sICH when compared to ACLVO. When adjusting for baseline differences, there was no significant difference between BAO vs ACLVO regarding rates of favorable outcome (aOR 0.986, 95%-CI 0.553 - 1.758). However, BAO were associated with increased rates of FR (aOR 2.146, 95%-CI 1.267 - 3.633). Predictors for FR were age, stroke severity, maneuver count and intracranial stenting. No significant heterogeneity on the relative merits of achieving successful recanalization on several outcome parameters were observed when comparing BAO and ACLVO., Conclusions: In selected patients, similar outcomes can be achieved in BAO and ACLVO patients treated with MT. Randomized controlled trials comparing patient selection and interventional strategies seem warranted to avoid FR., Trial Registration Number: NCT03496064., Competing Interests: Competing interests: UF is a consultant for Medtronic and Stryker and co-principal investigator of the SWIFT DIRECT trial (Medtronic). JG is a global principal investigator of STAR (Solitaire FR Thrombectomy for Acute Revascularisation), clinical event commitee member of the PROMISE study (European Registry on the ACE Reperfusion Catheters and the Penumbra System in the Treatment of Acute Ischemic Stroke; Penumbra), and a principal investigator and consultant for the SWIFT DIRECT study (Medtronic) and receives Swiss National Science Foundation (SNSF) grants for magnetic resonance imaging in stroke. LPi serves as a consultant for Balt, Microvention, and Penumbra. JK has received travel grants from Pfizer and Stryker. MRi serves as a consultant for Medtronic, Stryker, Anaconda, Apta Targets, and Perflow Medical and as a speaker for Neuravi. PMi has received funding for speaker honoraria from Boehringer. He has served on scientific advisory boards also for Boehringer. He has received research grants from Bristol-Myers Squibb, Boehringer, and the Swiss Heart Foundation. VMP is a consultant for Stryker (SC for DAWN trial), Penumbra (SC for PROMISE study), BALT (proctorship of products unrelated to ischemic stroke), Phenox, Rapid Medical, Neurovasc and receives research a grant from Philips. All the other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose- We determined the effect of sex on outcome after endovascular stroke thrombectomy in acute ischemic stroke, including lifelong disability outcomes. Methods- We analyzed patients treated with the Solitaire stent retriever in the combined SWIFT (Solitaire FR With the Intention for Thrombectomy), STAR (Solitaire FR Thrombectomy for Acute Revascularization), and SWIFT PRIME (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment) cohorts. Ordinal and logistic regression were used to examine known factors influencing outcome after endovascular stroke thrombectomy and study the effect of sex on the association between these factors and outcomes, including age and time to reperfusion. Years of optimal life after thrombectomy were defined as disability-adjusted life years and calculated by projecting disability through adjusted poststroke life expectancy by sex. Results- Among 389 patients treated with endovascular stroke thrombectomy, 55% were females, and median National Institutes of Health Stroke Scale was 17 (interquartile range, 8-28). There were no differences between females versus males in presenting deficit severity (National Institutes of Health Stroke Scale score, 17 versus 17, P=0.21), occlusion location (69% versus 64% M1, P=0.62), presenting infarct extent (Alberta Stroke Program Early CT Score 8 versus 8, P=0.24), rate of substantial reperfusion (Thrombolysis in Cerebral Infarction 2b/3, 87% versus 83%, P=0.37), onset to reperfusion time (294 versus 302 minutes, P=0.46). Despite older ages (69 versus 64, P<0.001) and higher rate of atrial fibrillation (45% versus 30%, P=0.002) for females compared with males, adjusted rates of functional independence at 90 days were similar (odds ratio, 1.0; 95% CI, 0.6-1.6). After adjusting for age at presentation and stroke severity, females had more years of optimal life (disability-adjusted life year) after endovascular stroke thrombectomy, 10.6 versus 8.5 years (P<0.001). Conclusions- Despite greater age and higher rate of atrial fibrillation, females experienced comparable functional outcomes and greater years of optimal life after intervention compared with males.

Background and Purpose- Understanding the influence of hyperglycemia on outcomes in terms of the pretreatment collateral status might contribute to the achievement of case-specific glucose management in acute ischemic stroke. We sought to investigate whether the glucose level can influence the pretreatment collateral status and functional outcomes of endovascular thrombectomy in acute ischemic stroke and whether the impact of hyperglycemia on outcomes can be modified by the pretreatment collateral status. Methods- We analyzed the Triple-S database, which includes individual patient data pooled from 3 prospective Solitaire stent retriever studies (SWIFT [Solitaire With the Intention for Thrombectomy], SWIFT PRIME [SWIFT as Primary Endovascular Treatment], and STAR [Solitaire Flow Restoration Thrombectomy for Acute Revascularization]). Patients were eligible if they had acute ischemic stroke with moderate to severe neurological deficits, harbored angiographically confirmed large vessel occlusion, and were treatable by endovascular thrombectomy within 8 hours of onset. Pretreatment catheter angiograms were scored for collateral grades by a core imaging laboratory. The main outcome was 3-month good outcome (modified Rankin Scale score of 0-2). Results- Angiographic data on collaterals were available in 309 patients (age, 67±12 years; glucose, 131±55 mg/dL). Overall, the glucose level at presentation was not associated with pretreatment collateral status but was significantly lower in patients with a good outcome at 90 days (124 versus 140 mg/dL). Collateral grades modified the effect of glucose on good outcomes at 90 days ( P int =0.03). Among patients with poor collaterals (collateral grades, 0-2), higher glucose levels did not alter the outcome, whereas among patients with good collaterals (3-4), higher glucose levels reduced the likelihood of a good outcome at 90 days (per 10 mg/dL increase: odds ratio, 0.81; 95% CI, 0.69-0.95). Conclusions- Our study revealed that higher glucose levels reduce the likelihood of a good outcome among patients with good collaterals, but their effects on the outcome are less significant for patients with poor collaterals. The results suggest that good collaterals at presentation may be targets for more intensive glucose control and future studies relating to glucose management.

Microcatheter contrast injection (MCI) prior to stent retriever deployment for the treatment of acute ischemic stroke may be useful for evaluation of distal anatomy and flow patterns beyond the occlusion. However, prior data from intra-arterialthrombolysis suggested that MCI increases the risk of intracranial hemorrhage (ICH). The safety and utility of MCI has not been investigated in the setting of thrombectomy., Methods: We analyzed the Solitaire With the Intention For Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME) trial to correlate pre-intervention MCI flow with collateral flow, and to investigate its impact on ICH and clinical outcome after thrombectomy with the Solitaire device., Results: MCI was noted in 52% (n=51) of patients with a prevalence for the M2 location of 71% (n=36). Dichotomized correlation demonstrated a strong inverse relationship for partial collaterals with good MCI flow (p=0.004; OR 8.25). None of the MCI variables (presence, number, or grades) correlated with ICH and clinical outcome. The most significant predictors of non-disabled outcome were higher Alberta Stroke Program early CT Score (ASPECTS) (OR 1.61; p=0.0361) and younger age (OR 0.922; p = 0.0109). Higher ASPECTS was also a strong predictor of lower ICH risk (OR 0.501, p=0.0078)., Conclusions: Collateral flow inversely correlated with MCI flow in the endovascular arm of the SWIFT PRIME trial. This finding warrants further validation in larger cohorts as MCI may be influenced by individual operator's technique and choice of syringe size. Evaluation of flow and distal anatomy with MCI prior to stent retriever deployment is safe with no evidence of an impact on ICH or clinical outcome., Clinical Trial Registration: NCT01657461: Post- results., Competing Interests: Competing interests: The main author has no competing interest. All co-authors are consultants for Medtronic Neurovascular., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background and Purpose: Flow arrest with balloon guide catheters (BGCs) is becoming increasingly recognized as critical to optimizing patient outcomes for mechanical thrombectomy. We performed a systematic review and meta-analysis of the literature for studies that compared angiographic and clinical outcomes for patients who underwent mechanical thrombectomy with and without BGCs., Materials and Methods: In April 2017 a literature search on BGC and mechanical thrombectomy for stroke was performed. All studies included patients treated with and without BGCs using modern techniques (ie, stent retrievers). Using random effects meta-analysis, we evaluated the following outcomes: first-pass recanalization, Thrombolysis In Cerebral Infarction (TICI) 3 recanalization, TICI 2b/3 recanalization, favorable outcome (modified Rankin Scale (mRS) 0-2), mortality, and mean number of passes and procedure time., Results: Five non-randomized studies of 2022 patients were included (1083 BGC group and 939 non-BGC group). Compared with the non-BGC group, patients treated with BGCs had higher odds of first-pass recanalization (OR 2.05, 95% CI 1.65 to 2.55), TICI 3 (OR 2.13, 95% CI 1.43 to 3.17), TICI 2b/3 (OR 1.54, 95% CI 1.21 to 1.97), and mRS 0-2 (OR 1.84, 95% CI 1.52 to 2.22). BGC-treated patients also had lower odds of mortality (OR 0.52, 95% CI 0.37 to 0.73) compared with non-BGC patients. The mean number of passes was significantly lower for BGC-treated patients (weighted mean difference -0.34, 95% CI-0.47 to -0.22). Mean procedure time was also significantly shorter for BGC-treated patients (weighted mean difference -7.7 min, 95% CI-9.0to -6.4)., Conclusions: Non-randomized studies suggest that BGC use during mechanical thrombectomy for acute ischemic stroke is associated with superior clinical and angiographic outcomes. Further randomized trials are needed to confirm the results of this study., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy., Methods: We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 [death] to 10 [no symptoms or disability]) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating more severe disability) at 90 days., Results: A total of 206 patients were enrolled; 107 were assigned to the thrombectomy group and 99 to the control group. At 31 months, enrollment in the trial was stopped because of the results of a prespecified interim analysis. The mean score on the utility-weighted modified Rankin scale at 90 days was 5.5 in the thrombectomy group as compared with 3.4 in the control group (adjusted difference [Bayesian analysis], 2.0 points; 95% credible interval, 1.1 to 3.0; posterior probability of superiority, >0.999), and the rate of functional independence at 90 days was 49% in the thrombectomy group as compared with 13% in the control group (adjusted difference, 33 percentage points; 95% credible interval, 24 to 44; posterior probability of superiority, >0.999). The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups (6% in the thrombectomy group and 3% in the control group, P=0.50), nor did 90-day mortality (19% and 18%, respectively; P=1.00)., Conclusions: Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone. (Funded by Stryker Neurovascular; DAWN ClinicalTrials.gov number, NCT02142283 .).

Background and Purpose: The majority of patients enrolled in SWIFT PRIME trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke) had computed tomographic perfusion (CTP) imaging before randomization; 34 patients were randomized after magnetic resonance imaging (MRI)., Methods: Patients with middle cerebral artery and distal carotid occlusions were randomized to treatment with tPA (tissue-type plasminogen activator) alone or tPA+stentriever thrombectomy. The primary outcome was the distribution of the modified Rankin Scale score at 90 days. Patients with the target mismatch profile for enrollment were identified on MRI and CTP., Results: MRI selection was performed in 34 patients; CTP in 139 patients. Baseline National Institutes of Health Stroke Scale score was 17 in both groups. Target mismatch profile was present in 95% (MRI) versus 83% (CTP). A higher percentage of the MRI group was transferred from an outside hospital ( P =0.02), and therefore, the time from stroke onset to randomization was longer in the MRI group ( P =0.003). Time from emergency room arrival to randomization did not differ in CTP versus MRI-selected patients. Baseline ischemic core volumes were similar in both groups. Reperfusion rates (>90%/TICI [Thrombolysis in Cerebral Infarction] score 3) did not differ in the stentriever-treated patients in the MRI versus CTP groups. The primary efficacy analysis (90-day mRS score) demonstrated a statistically significant benefit in both subgroups (MRI, P =0.02; CTP, P =0.01). Infarct growth was reduced in the stentriever-treated group in both MRI and CTP groups., Conclusions: Time to randomization was significantly longer in MRI-selected patients; however, site arrival to randomization times were not prolonged, and the benefits of endovascular therapy were similar., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461., (© 2017 American Heart Association, Inc.)

Importance: Mechanical thrombectomy (MT) improves clinical outcomes in patients with acute ischemic stroke (AIS) caused by a large vessel occlusion. However, it is not known whether intravenous thrombolysis (IVT) is of added benefit in patients undergoing MT., Objective: To examine whether treatment with IVT before MT with a stent retriever is beneficial in patients undergoing MT., Design, Setting, and Participants: This post hoc analysis used data from 291 patients treated with MT included in 2 large, multicenter, prospective clinical trials that evaluated MT for AIS (Solitaire With the Intention for Thrombectomy performed from January 1, 2010, through December 31, 2011, and Solitaire Flow Restoration Thrombectomy for Acute Revascularization from January 1, 2010, through December 31, 2012). An independent core laboratory scored the radiologic outcomes in each trial., Interventions: Patients were treated with IVT with tissue plasminogen activator followed by MT (IVT and MT group) with the use of a stent retriever or MT with a stent retriever alone (MT group)., Main Outcomes and Measures: Successful reperfusion, functional independence (modified Rankin Scale score of 0-2) and mortality at 90 days, symptomatic intracranial hemorrhage, emboli to new territory, and vasospasm were compared., Results: Of 291 patients included in the analysis, 160 (55.0%) underwent IVT and MT (mean [SD] age, 67 [13] years; 97 female [60.6%]), and 131 (45.0%) underwent MT alone (mean [SD] age, 69 [12] years; 71 [55.7%] female). Median Alberta Stroke Program Early CT Score at baseline was lower in the IVT and MT group (8 vs 9, P = .04). There was no statistically significant difference in the duration from symptom onset to groin puncture (254 minutes for the IVT and MT group vs 262 minutes for the MT group, P = .10). The number of passes, rate of successful reperfusion, functional independence at 90 days, mortality at 90 days, and emboli to new territory were also similar among groups. Symptomatic intracranial hemorrhage (1% vs 4%) and parenchymal hemorrhages type 1 (1% vs 3%) or type 2 (1% vs 2%) did not differ significantly (P = .25). Vasospasm occurred more often in patients who received IVT and MT vs MT alone (27% vs 14%, P = .006). In multivariate analysis, no statistically significant association was observed between IVT and MT vs MT alone for any of the outcomes., Conclusions and Relevance: The results indicate that treatment of patients experiencing AIS due to a large vessel occlusion with IVT before MT does not appear to provide a clinical benefit over MT alone. A randomized clinical trial seems warranted., Trial Registration: clinicaltrials.gov Identifiers: NCT01054560 and NCT01327989.

Background and Purpose: Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator (SST+tPA) compared with tPA. Previous studies suggested that this strategy may be cost-effective, but models were derived from pooled data and older assumptions., Methods: In this prospective economic substudy conducted alongside the SWIFT-PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), in-trial costs were measured for patients using detailed medical resource utilization and hospital billing data. Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension questionnaire. Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors., Results: Index hospitalization costs were $17 183 per patient higher for SST+tPA than for tPA ($45 761 versus $28 578; P<0.001), driven by initial procedure costs. Between discharge and 90 days, costs were $4904 per patient lower for SST+tPA than for tPA ($11 270 versus $16 174; P=0.014); total 90-day costs remained higher with SST+tPA ($57 031 versus $44 752; P<0.001). Higher utility values for SST+tPA led to higher in-trial quality-adjusted life years (0.131 versus 0.105; P=0.005). In lifetime projections, SST+tPA was associated with substantial gains in quality-adjusted life years (6.79 versus 5.05), cost savings of $23 203 per patient and was economically dominant when compared with tPA in 90% of bootstrap replicates., Conclusions: Among patients with acute ischemic stroke enrolled in the SWIFT-PRIME trial, SST increased initial treatment costs, but was projected to improve quality-adjusted life-expectancy and reduce healthcare costs over a lifetime horizon compared with tPA., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461., (© 2016 American Heart Association, Inc.)

Background: In 2015, five randomised trials showed efficacy of endovascular thrombectomy over standard medical care in patients with acute ischaemic stroke caused by occlusion of arteries of the proximal anterior circulation. In this meta-analysis we, the trial investigators, aimed to pool individual patient data from these trials to address remaining questions about whether the therapy is efficacious across the diverse populations included., Methods: We formed the HERMES collaboration to pool patient-level data from five trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA) done between December, 2010, and December, 2014. In these trials, patients with acute ischaemic stroke caused by occlusion of the proximal anterior artery circulation were randomly assigned to receive either endovascular thrombectomy within 12 h of symptom onset or standard care (control), with a primary outcome of reduced disability on the modified Rankin Scale (mRS) at 90 days. By direct access to the study databases, we extracted individual patient data that we used to assess the primary outcome of reduced disability on mRS at 90 days in the pooled population and examine heterogeneity of this treatment effect across prespecified subgroups. To account for between-trial variance we used mixed-effects modelling with random effects for parameters of interest. We then used mixed-effects ordinal logistic regression models to calculate common odds ratios (cOR) for the primary outcome in the whole population (shift analysis) and in subgroups after adjustment for age, sex, baseline stroke severity (National Institutes of Health Stroke Scale score), site of occlusion (internal carotid artery vs M1 segment of middle cerebral artery vs M2 segment of middle cerebral artery), intravenous alteplase (yes vs no), baseline Alberta Stroke Program Early CT score, and time from stroke onset to randomisation., Findings: We analysed individual data for 1287 patients (634 assigned to endovascular thrombectomy, 653 assigned to control). Endovascular thrombectomy led to significantly reduced disability at 90 days compared with control (adjusted cOR 2.49, 95% CI 1.76-3.53; p<0.0001). The number needed to treat with endovascular thrombectomy to reduce disability by at least one level on mRS for one patient was 2.6. Subgroup analysis of the primary endpoint showed no heterogeneity of treatment effect across prespecified subgroups for reduced disability (pinteraction=0.43). Effect sizes favouring endovascular thrombectomy over control were present in several strata of special interest, including in patients aged 80 years or older (cOR 3.68, 95% CI 1.95-6.92), those randomised more than 300 min after symptom onset (1.76, 1.05-2.97), and those not eligible for intravenous alteplase (2.43, 1.30-4.55). Mortality at 90 days and risk of parenchymal haematoma and symptomatic intracranial haemorrhage did not differ between populations., Interpretation: Endovascular thrombectomy is of benefit to most patients with acute ischaemic stroke caused by occlusion of the proximal anterior circulation, irrespective of patient characteristics or geographical location. These findings will have global implications on structuring systems of care to provide timely treatment to patients with acute ischaemic stroke due to large vessel occlusion., Funding: Medtronic., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background and Purpose: Imaging findings can predict outcomes in patients with acute stroke. Relationships between imaging findings and clinical and imaging outcomes in patients randomized to intravenous tissue-type plasminogen activator-alone versus tissue-type plasminogen activator plus endovascular therapy (Solitaire device) in the Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) study were assessed., Methods: We evaluated associations between imaging assessments (baseline mismatch profiles/ischemic core volumes and successful reperfusion) with imaging outcomes (27-hour infarct volume/growth) and clinical outcomes (modified Rankin Scale scores at 90 days). Imaging variables that predict favorable clinical outcomes were assessed in both univariate and multivariate models., Results: One hundred and ninety-five patients were included. Successful reperfusion and infarct volume (assessed at 27 hours) were powerful independent predictors of favorable clinical outcomes (modified Rankin Scale score of 0-2 at 90 days). Patients with the target mismatch profile at baseline had a higher rate of reperfusion, lesser infarct growth, smaller infarct volumes, and better clinical outcomes in the Solitaire plus tissue-type plasminogen activator (intervention) group than those in the tissue-type plasminogen activator-alone (control) group. Patients with larger mismatch volumes at baseline had a trend toward better treatment response in the intervention group than patients who had smaller (<50 mL) mismatch volumes., Conclusions: Patients who achieved reperfusion had substantially more favorable clinical and imaging outcomes in both the intervention and the control groups. Infarct volume at 27 hours strongly correlated with clinical outcome at 90 days in both treatment groups. SWIFT PRIME patients with the target mismatch profile had a highly favorable response to endovascular therapy on both clinical and imaging outcomes. Both reperfusion and infarct volumes at 27 hours were powerful and independent predictors of 90-day clinical outcomes., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461., (© 2015 American Heart Association, Inc.)

Background: Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, less than 40% regain functional independence when treated with intravenous tissue plasminogen activator (t-PA) alone. Thrombectomy with the use of a stent retriever, in addition to intravenous t-PA, increases reperfusion rates and may improve long-term functional outcome., Methods: We randomly assigned eligible patients with stroke who were receiving or had received intravenous t-PA to continue with t-PA alone (control group) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset (intervention group). Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemic-core lesions. The primary outcome was the severity of global disability at 90 days, as assessed by means of the modified Rankin scale (with scores ranging from 0 [no symptoms] to 6 [death])., Results: The study was stopped early because of efficacy. At 39 centers, 196 patients underwent randomization (98 patients in each group). In the intervention group, the median time from qualifying imaging to groin puncture was 57 minutes, and the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P<0.001). The rate of functional independence (modified Rankin scale score, 0 to 2) was higher in the intervention group than in the control group (60% vs. 35%, P<0.001). There were no significant between-group differences in 90-day mortality (9% vs. 12%, P=0.50) or symptomatic intracranial hemorrhage (0% vs. 3%, P=0.12)., Conclusions: In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days. (Funded by Covidien; SWIFT PRIME ClinicalTrials.gov number, NCT01657461.).

Rationale: Early reperfusion in patients experiencing acute ischemic stroke is critical, especially for patients with large vessel occlusion who have poor prognosis without revascularization. Solitaire™ stent retriever devices have been shown to immediately restore vascular perfusion safely, rapidly, and effectively in acute ischemic stroke patients with large vessel occlusions., Aim: The aim of the study was to demonstrate that, among patients with large vessel, anterior circulation occlusion who have received intravenous tissue plasminogen activator, treatment with Solitaire revascularization devices reduces degree of disability 3 months post stroke., Design: The study is a global multicenter, two-arm, prospective, randomized, open, blinded end-point trial comparing functional outcomes in acute ischemic stroke patients who are treated with either intravenous tissue plasminogen activator alone or intravenous tissue plasminogen activator in combination with the Solitaire device. Up to 833 patients will be enrolled., Procedures: Patients who have received intravenous tissue plasminogen activator are randomized to either continue with intravenous tissue plasminogen activator alone or additionally proceed to neurothrombectomy using the Solitaire device within six-hours of symptom onset., Study Outcomes: The primary end-point is 90-day global disability, assessed with the modified Rankin Scale (mRS). Secondary outcomes include mortality at 90 days, functional independence (mRS ≤ 2) at 90 days, change in National Institutes of Health Stroke Scale at 27 h, reperfusion at 27 h, and thrombolysis in cerebral infarction 2b/3 flow at the end of the procedure., Analysis: Statistical analysis will be conducted using simultaneous success criteria on the overall distribution of modified Rankin Scale (Rankin shift) and proportions of subjects achieving functional independence (mRS 0-2)., (© 2015 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.)

Background and Purpose: Mechanical thrombectomy using stent retriever devices have been advocated to increase revascularization in intracranial vessel occlusion. We present the results of a large prospective study on the use of the Solitaire Flow Restoration in patients with acute ischemic stroke., Methods: Solitaire Flow Restoration Thrombectomy for Acute Revascularization was an international, multicenter, prospective, single-arm study of Solitaire Flow Restoration thrombectomy in patients with large vessel anterior circulation strokes treated within 8 hours of symptom onset. Strict criteria for site selection were applied. The primary end point was the revascularization rate (thrombolysis in cerebral infarction ≥2b) of the occluded vessel as determined by an independent core laboratory. The secondary end point was the rate of good functional outcome (defined as 90-day modified Rankin scale, 0-2)., Results: A total of 202 patients were enrolled across 14 comprehensive stroke centers in Europe, Canada, and Australia. The median age was 72 years, 60% were female patients. The median National Institute of Health Stroke Scale was 17. Most proximal intracranial occlusion was the internal carotid artery in 18%, and the middle cerebral artery in 82%. Successful revascularization was achieved in 79.2% of patients. Device and procedure-related severe adverse events were found in 7.4%. Favorable neurological outcome was found in 57.9%. The mortality rate was 6.9%. Any intracranial hemorrhagic transformation was found in 18.8% of patients, 1.5% were symptomatic., Conclusions: In this single-arm study, treatment with the Solitaire Flow Restoration device in intracranial anterior circulation occlusions results in high rates of revascularization, low risk of clinically relevant procedural complications, and good clinical outcomes in combination with low mortality at 90 days., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT01327989.

ObjectiveTo assess whether the association between reperfusion and improved clinical outcomes after stroke differs depending on the site of the arterial occlusive lesion (AOL).MethodsWe pooled data from Solitaire With the Intention for Thrombectomy (SWIFT), Solitaire FR Thrombectomy for Acute Revascularisation (STAR), Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), and Interventional Management of Stroke Trial (IMS III) to compare the strength of the associations between reperfusion and clinical outcomes in patients with internal carotid artery (ICA), proximal middle cerebral artery (MCA) (M1), and distal MCA (M2/3/4) occlusions.ResultsAmong 710 included patients, the site of the AOL was the ICA in 161, the proximal MCA in 389, and the distal MCA in 160 patients (M2 = 131, M3 = 23, and M4 = 6). Reperfusion was associated with an increase in the rate of good functional outcome (modified Rankin Scale [mRS] score 0-2) in patients with ICA (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.7-7.2) and proximal MCA occlusions (OR 6.2, 95% CI 3.8-10.2), but not in patients with distal MCA occlusions (OR 1.4, 95% CI 0.8-2.6). Among patients with M2 occlusions, a subset of the distal MCA cohort, reperfusion was associated with excellent functional outcome (mRS 0-1; OR 2.2, 95% CI 1.0-4.7).ConclusionsThe association between endovascular reperfusion and better clinical outcomes is more profound in patients with ICA and proximal MCA occlusions compared to patients with distal MCA occlusions. Because there are limited data from randomized controlled trials on the effect of endovascular therapy in patients with distal MCA occlusions, these results underscore the need for inclusion of this subgroup in future endovascular therapy trials.

RationaleEarly reperfusion in patients experiencing acute ischemic stroke is critical, especially for patients with large vessel occlusion who have poor prognosis without revascularization. Solitaire™ stent retriever devices have been shown to immediately restore vascular perfusion safely, rapidly, and effectively in acute ischemic stroke patients with large vessel occlusions.AimThe aim of the study was to demonstrate that, among patients with large vessel, anterior circulation occlusion who have received intravenous tissue plasminogen activator, treatment with Solitaire revascularization devices reduces degree of disability 3 months post stroke.DesignThe study is a global multicenter, two-arm, prospective, randomized, open, blinded end-point trial comparing functional outcomes in acute ischemic stroke patients who are treated with either intravenous tissue plasminogen activator alone or intravenous tissue plasminogen activator in combination with the Solitaire device. Up to 833 patients will be enrolled.ProceduresPatients who have received intravenous tissue plasminogen activator are randomized to either continue with intravenous tissue plasminogen activator alone or additionally proceed to neurothrombectomy using the Solitaire device within six-hours of symptom onset.Study outcomesThe primary end-point is 90-day global disability, assessed with the modified Rankin Scale (mRS). Secondary outcomes include mortality at 90 days, functional independence (mRS ≤ 2) at 90 days, change in National Institutes of Health Stroke Scale at 27 h, reperfusion at 27 h, and thrombolysis in cerebral infarction 2b/3 flow at the end of the procedure.AnalysisStatistical analysis will be conducted using simultaneous success criteria on the overall distribution of modified Rankin Scale (Rankin shift) and proportions of subjects achieving functional independence (mRS 0-2).

Rationale: Whether treatment with intravenous alteplase prior to mechanical thrombectomy (MT) in acute ischemic stroke patients with large vessel occlusion is beneficial remains unclear. Aim: To determine whether patients experiencing acute ischemic stroke due to occlusion of the intracranial internal carotid artery or the M1 segment of the middle cerebral artery who are referred to an endovascular stroke center and who are candidates for intravenous alteplase will have non-inferior functional outcome at 90 days when treated with MT alone (direct MT) with stent retrievers compared to patients treated with combined intravenous thrombolysis (IVT) with alteplase plus MT (IVT + MT) with stent retrievers. Sample size: To randomize 404 patients 1:1 to direct MT or combined IVT+MT. Methods and design: A multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) trial utilizing an adaptive statistical design. Outcomes: The primary efficacy endpoint is functional independence (modified Rankin Scale 0–2) at 90 days. Secondary clinical efficacy outcomes include change in National Institutes of Health Stroke Scale score from baseline to day 1 and health-related quality of life at 90 days. Secondary technical efficacy outcomes include successful reperfusion prior to start of MT and time from randomization to successful reperfusion. Safety outcomes include all serious adverse events, symptomatic intracranial hemorrhage, and mortality up to 90 days. Discussion: SWIFT DIRECT will inform physicians whether direct MT in acute ischemic stroke patients with large vessel occlusion is equally or more efficacious than combined treatment with intravenous alteplase and MT. Trial registration: ClinicalTrials.gov Identifier: NCT03192332 [ABSTRACT FROM AUTHOR]

Background and aim: Mechanical thrombectomy (MT) for large vessel occlusion often requires multiple passes to retrieve the entire thrombus load. In this multi-institutional study we sought to examine the composition of thrombus fragments retrieved with each pass during MT. Methods: Patients who required multiple passes during thrombectomy were included. Histopathological evaluation of thrombus fragments retrieved from each pass was performed using Martius Scarlet Blue staining and the composition of each thrombus component including RBC, fibrin and platelet was determined using image analysis software. Results: 154 patients underwent MT and 868 passes was performed which resulted in 263 thrombus fragments retrieval. The analysis of thrombus components per pass showed higher RBC, lower fibrin and platelet composition in the pass 1 and 2 when compared to pass 3 and passes 4 or more combined (P values <0.05). There were no significant differences between thrombus fragments retrieved in pass 1 and pass 2 in terms of RBC, WBC, fibrin, and platelet composition (P values >0.05). Similarly, when each composition of thrombus fragments retrieved in pass 3 and passes 4 or more combined were compared with each other, no significant difference was noted (P values >0.05). Conclusion: Our findings confirm that thrombus fragments retrieved with each pass differed significantly in histological content. Fragments in the first passes were associated with lower fibrin and platelet composition compared to fragments retrieved in passes three and four or higher. Also, thrombus fragments retrieved after failed pass were associated with higher fibrin and platelet components. [ABSTRACT FROM AUTHOR]

Background: The indications for mechanical thrombectomy in acute ischemic stroke continue to broaden, leading neurointerventionalists to treat vessel occlusions at increasingly distal locations farther in time from stroke onset. Accessing these smaller vessels raises the concern of iatrogenic subarachnoid hemorrhage (SAH) owing to increasing complexity in device navigation and retrieval. This study aims to determine the prevalence of SAH following mechanical thrombectomy, associated predictors, and resulting functional outcomes using a multicenter registry and compare this with a systematic review and meta-analysis of the literature. Methods: Data from STRATIS (The Systematic Evaluation of Patients Treated with Neurothrombectomy Devices for Acute Ischemic Stroke) registry were analyzed dichotomized by the presence or absence of SAH after thrombectomy. Only patients with 24-h post-procedural neuroimaging were included (n = 841). Multivariable logistic regression was performed to identify significant predictors of SAH. A systematic review and random-effects meta-analysis was also conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) protocol. Results: The prevalence of post-thrombectomy SAH was 5.23% in STRATIS with 15.9% (1.84% overall) experiencing neurological decline. Distal location of vessel occlusion (OR 3.41 [95% CI: 1.75–6.63], p < 0.001) and more than 3 device passes (OR 1.34 [95% CI: 1.09–1.64], p = 0.01) were associated with a higher probability of SAH in contrast to a reduction with administration of intravenous tissue plasminogen activator (tPA) (OR 0.48 [95% CI: 0.26–0.89], p = 0.02). There was a trend toward a higher discharge NIHSS (8.3 ± 8.7 vs. 5.3 ± 6.6, p = 0.07) with a significantly reduced proportion achieving functional independence at 90 days (modified Rankin Score 0–2: 32.5% vs. 57.8%, p = 0.002) in SAH patients. Pooled analysis of 10,126 patients from 6 randomized controlled trials and 64 observational studies demonstrated a prevalence of 5.85% [95% CI: 4.51–7.34%, I 2: 85.2%]. Only location of vessel occlusion was significant for increased odds of SAH at distal sites (OR 2.89 [95% CI: 1.14, 7.35]). Conclusions: Iatrogenic SAH related to mechanical thrombectomy is more common with treatment of distally-situated occlusions and multiple device passes. While low in overall prevalence, its effect is not benign with fewer patients reaching post-procedural functional independence, particularly if symptomatic. [ABSTRACT FROM AUTHOR]

Background and Purpose: Given recent evidence suggesting the clot composition may be associated with revascularization outcomes and stroke etiology, clot composition research has been a topic of growing interest. It is currently unclear what effect, if any, pre-thrombectomy thrombolysis has on clot composition. Understanding this association is important as it is a potential confounding variable in clot composition research. We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients who did and did not receive pre-treatment tPA to study the effect of tPA on clot composition.Materials and Methods: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using Martius Scarlett Blue (MSB) staining and area of the clot was also measured on the gross photos. Student's t test was used for continuous variables and chi-squared test for categorical variables.Results: A total of 1430 patients were included in this study. Mean age was 68.4±13.5 years. Overall rate of TICI 2c/3 was 67%. A total of 517 patients received tPA (36%) and 913 patients did not (64%). Mean RBC density for the tPA group was 42.97±22.62% compared to 42.80±23.18% for the non-tPA group (P=0.89). Mean WBC density for the tPA group was 3.74±2.60% compared to 3.42±2.21% for the non-tPA group (P=0.012). Mean fibrin density for the tPA group was 26.52±15.81% compared to 26.53±15.34% for the non-tPA group (P=0.98). Mean platelet density for the tPA group was 26.22±18.60% compared to 26.55±19.47% for the non-tPA group (P=0.75). tPA group also had significantly smaller clot area compared to non-tPA group.Conclusions: Our study 1430 retrieved emboli and ischemic stroke patients shows no interaction between tPA administration and clot composition. These findings suggest that tPA does not result in any histological changes in clot composition. [ABSTRACT FROM AUTHOR]