Thrombectomy for Stroke With Large Infarct on Noncontrast CT: The TESLA Randomized Clinical Trial.

Importance: Recent large infarct thrombectomy trials used heterogeneous imaging modalities and time windows for patient selection. Noncontrast computed tomographic (CT) scan is the most common stroke imaging approach. It remains uncertain whether thrombectomy is effective for patients with large infarcts identified using noncontrast CT alone within 24 hours of stroke onset. Objective: To evaluate the effect of thrombectomy in patients with a large infarct on a noncontrast CT scan within 24 hours of onset. Design, Setting, and Participants: Open-label, blinded-end point, bayesian-adaptive randomized trial with interim analyses for early stopping (futility or success) or population enrichment, which was conducted at 47 US academic and community-based stroke thrombectomy centers. Three hundred patients presenting within 24 hours with anterior-circulation, large-vessel occlusion and large infarct on noncontrast CT scan, with Alberta Stroke Program Early CT Scores of 2 to 5, were randomized to undergo thrombectomy or usual care. Enrollment occurred July 16, 2019 to October 17, 2022; final follow-up, January 25, 2023. Intervention: The intervention patients (n = 152) underwent endovascular treatment using standard thrombectomy devices and usual medical care. Control patients (n = 148) underwent usual medical care alone. Main Outcomes and Measures: The primary efficacy end point was improvement in 90-day functional outcome measured using mean utility-weighted modified Rankin Scale (UW-mRS) scores (range, 0 [death or severe disability] to 10 [no symptoms]; minimum clinically important difference, 0.3). A bayesian model determined the posterior probability that the intervention would be superior to usual care; statistical significance was a 1-sided posterior probability of .975 or more. The primary adverse event end point was 90-day mortality; secondary adverse event end points included symptomatic intracranial hemorrhage and radiographic intracranial hemorrhage. Results: The trial enrolled 300 patients (152 intervention, 148 control; 138 females [46%]; median age, 67 years), without early stopping or enrichment; 297 patients completed the 90-day follow-up. The mean (SD) 90-day UW-mRS score was 2.93 (3.39) for the intervention group vs 2.27 (2.98) for the control group with an adjusted difference of 0.63 (95% credible interval [CrI], -0.09 to 1.34; posterior probability for superiority of thrombectomy, .96). The 90-day mortality was similar between groups: 35.3% (53 of 150) for the intervention group vs 33.3% (49 of 147) for the control group. Six of 151 patients (4.0%) in the intervention group and 2 of 149 (1.3%) in the control group experienced 24-hour symptomatic intracranial hemorrhage. Fourteen patients of 148 (9.5%) in the intervention group vs 4 of 146 (2.7%) in the control group experienced parenchymal hematoma type 1 hemorrhages; 14 (9.5%) in the intervention group vs 5 (3.4%) in the control group experienced parenchymal hematoma type 2 hemorrhages; and 24 (16.2%) in the intervention group vs 9 (6.2%) in the control group experienced subarachnoid hemorrhages. Conclusions and Relevance: Among patients with a large infarct on noncontrast CT within 24 hours, thrombectomy did not demonstrate improvement in functional outcomes. But the width of the credible interval around the effect estimate includes the possibility of both no important effect and a clinically relevant benefit, so the potential role of thrombectomy with this imaging approach and time window will likely require additional study. Trial Registration: ClinicalTrials.gov Identifier: NCT03805308.

Impact of Time to Treatment on Endovascular Thrombectomy Outcomes in the Early Versus Late Treatment Time Windows.

BACKGROUND: The impact of time to treatment on outcomes of endovascular thrombectomy (EVT) especially in patients presenting after 6 hours from symptom onset is not well characterized. We studied the differences in characteristics and treatment timelines of EVT-treated patients participating in the Florida Stroke Registry and aimed to characterize the extent to which time impacts EVT outcomes in the early and late time windows. METHODS: Prospectively collected data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. Participants were EVT patients with onset-to-puncture time (OTP) of ≤24 hours and categorized into early window treated (OTP ≤6 hours) and late window treated (OTP >6 and ≤24 hours). Association between OTP and favorable discharge outcomes (independent ambulation, discharge home and to acute rehabilitation facility) as well as symptomatic intracerebral hemorrhage and in-hospital mortality were examined using multilevel-multivariable analysis with generalized estimating equations. RESULTS: Among 8002 EVT patients (50.9% women; median age [±SD], 71.5 [±14.5] years; 61.7% White, 17.5% Black, and 21% Hispanic), 34.2% were treated in the late time window. Among all EVT patients, 32.4% were discharged home, 23.5% to rehabilitation facility, 33.7% ambulated independently at discharge, 5.1% had symptomatic intracerebral hemorrhage, and 9.2% died. As compared with the early window, treatment in the late window was associated with lower odds of independent ambulation (odds ratio [OR], 0.78 [0.67-0.90]) and discharge home (OR, 0.71 [0.63-0.80]). For every 60-minute increase in OTP, the odds of independent ambulation reduced by 8% (OR, 0.92 [0.87-0.97]; P<0.001) and 1% (OR, 0.99 [0.97-1.02]; P=0.5) and the odds of discharged home reduced by 10% (OR, 0.90 [0.87-0.93]; P<0.001) and 2% (OR, 0.98 [0.97-1.00]; P=0.11) in the early and late windows, respectively. CONCLUSIONS: In routine practice, just over one-third of EVT-treated patients independently ambulate at discharge and only half are discharged to home/rehabilitation facility. Increased time from symptom onset to treatment is significantly associated with lower chance of independent ambulation and ability to be discharged home after EVT in the early time window.

Nationally Certified Stroke Centers Outperform Self-Attested Stroke Centers in the Florida Stroke Registry.

BACKGROUND: The Florida Stroke Act, signed into law in 2004, set criteria for Comprehensive Stroke Centers (CSC). For a set time period, Florida hospitals were permitted to either receive national certification (NC) or could self-attest (SA) as fulfilling CSC criteria. The aim of this project was to evaluate the quality of ischemic stroke care in NC versus SA stroke centers in Florida, using well-known, guideline-driven ischemic stroke outcome metrics. METHODS: A total of 37 CSCs (74% of Florida CSCs) in the Florida Stroke Registry from January 2013 through December 2018 were analyzed, including 19 SA CSCs and 18 NC (13 CSCs and 5 Thrombectomy-Capable Stroke Center). Hospital- and patient-level characteristics and stroke metrics were evaluated, adjusting for demographics, medical comorbidities, and stroke severity. RESULTS: A total of 78 424 acute ischemic stroke cases, 36 089 from SA CSCs and 42 335 from NC CSC/Thrombectomy-Capable Stroke Centers were analyzed. NC centers had older patients (73 [61-83] versus 71 [60-81]; P<0.001) with more severe strokes (median National Institutes of Health Stroke Scale score of 5 versus 4; P<0.001). NC had higher intravenous tissue-type plasminogen activator utilization (15% versus 13%; P<0.001), endovascular treatment (10% versus 7%; P<0.001) and faster median door-to-computed tomography (23 minutes [11-73] versus 31 [12-78]; P<0.001), door-to-needle (37 minutes [26-50] versus 45 [34-58]; P<0.001) and door-to-puncture times (77 minutes [50-113] versus 93 [62-140]; P<0.001). In adjusted analysis, patients arriving to NC hospitals by 3 hours were more likely to get intravenous tissue-type plasminogen activator in the 3- to 4.5-hour window (adjusted odds ratio, 1.87 [95% CI, 1.30-2.68]; P=0.001) and more likely to be treated with intravenous tissue-type plasminogen activator within 45 minutes (adjusted odds ratio, 1.61 [95% CI, 1.04-2.50]; P=0.04) compared with SA CSCs. CONCLUSIONS: Among Florida-Stroke Registry CSCs, acute ischemic stroke performance and treatment measures at NC centers are superior to SA CSCs. These findings have implications for stroke systems of care in Florida and support legislation updates requiring NC and removal of SA claims.

IV Thrombolysis Initiated Before Transfer for Endovascular Stroke Thrombectomy: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: The role of IV thrombolysis (IVT) in patients with large vessel occlusions (LVOs) administered before transfer from a primary stroke center (PSC) to a comprehensive stroke center (CSC) is questioned. METHODS: We included observational studies of patients with an LVO receiving IVT at a PSC before their endovascular thrombectomy (EVT) transfer compared with those receiving EVT alone. Efficacy outcomes included excellent or good functional outcomes (modified Rankin Scale [mRS] scores of 0-1 or 0-2, respectively) and reduced disability (mRS shift analysis) at 3 months. Safety outcomes included symptomatic intracranial hemorrhage (sICH) within 48 hours and 3-month all-cause mortality. Associations are reported with crude odds ratios (ORs) and adjusted ORs (aORs). RESULTS: We identified 6 studies, including 1,723 participants (mean age: 71 years, 51% women; 53% treated with IVT at a PSC). The mean onset-to-groin puncture time did not differ between the 2 groups (mean difference: -20 minutes, 95% CI -115.89 to 76.04). Patients receiving IVT before transfer had higher odds of 3-month reduced disability (common OR = 1.98, 95% CI 1.17-3.35), excellent (OR = 1.70, 95% CI 1.28-2.26), and good (OR = 1.62.95% CI 1.15-2.29) functional outcomes, with no increased sICH (OR = 0.87, 95% CI 0.54-1.39) or mortality (OR = 0.55, 95% CI 0.37-0.83) risks. In the adjusted analyses, patients receiving IVT at a PSC had higher odds of excellent functional outcome (aOR = 1.32, 95% CI 1.00-1.74) and a lower probability for mortality (aOR = 0.50, 95% CI 0.27-0.93). DISCUSSION: Patients with LVO receiving IVT at a PSC before an EVT transfer have a higher likelihood of excellent functional recovery and lower odds of mortality, with no increase in sICH and onset-to-groin puncture times, compared with those transferred for EVT without previously receiving IVT.

Predicting Functional Outcome Using 24-Hour Post-Treatment Characteristics: Application of Machine Learning Algorithms in the STRATIS Registry.

FOR SOCIAL MEDIA: @AliciaCastongu2, @FazalZaidi9, @oozaidat, @Mouhammad_Jumaa OBJECTIVE: Machine learning (ML) algorithms have emerged as powerful predictive tools in the field stroke. Here, we examine the predictive accuracy of ML models for predicting functional outcomes using 24-hour post-treatment characteristics in the Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke (STRATIS) Registry. METHODS: ML models, adaptive boost, random forest (RF), classification and regression trees (CART), C5.0 decision tree (C5.0), support vector machine (SVM), least absolute shrinkage and selection operator (LASSO), and logistic regression (LR), and traditional LR models were used to predict 90-day functional outcome (modified Rankin Scale score 0-2). Twenty-four-hour National Institutes of Health Stroke Scale (NIHSS) was examined as a continuous or dichotomous variable in all models. Model accuracy was assessed using the area under characteristic curve (AUC). RESULTS: The 24-hour NIHSS score was a top-predictor of functional outcome in all models. ML models using the continuous 24-hour NIHSS scored showed moderate-to-good predictive performance (range mean AUC: 0.76-0.92); however, RF (AUC: 0.92 ± 0.028) outperformed all ML models, except LASSO (AUC: 0.89 ± 0.023, p = 0.0958). Importantly, RF demonstrated a significantly higher predictive value than LR (AUC: 0.87 ± 0.031, p = 0.048) and traditional LR (AUC: 85 ± 0.06, p = 0.035) when using the 24-hour continuous NIHSS score. Predictive accuracy was similar between the 24-hour NIHSS score dichotomous and continuous ML models. INTERPRETATION: In this substudy, we found similar predictive accuracy for functional outcome when using the 24-hour NIHSS score as a continuous or dichotomous variable in ML models. ML models had moderate-to-good predictive accuracy, with RF outperforming LR models. External validation of these ML models is warranted. ANN NEUROL 2023;93:40-49.

Economic impact of the first pass effect in mechanical thrombectomy for acute ischaemic stroke treatment in Spain: a cost-effectiveness analysis from the national health system perspective.

OBJECTIVE: The mechanical thrombectomy (MT) benefit is related to the degree of reperfusion achieved. First pass effect (FPE) is defined as complete/near revascularisation of the large-vessel occlusion (modified Thrombolysis in Cerebral Infarction (mTICI) 2c-3) after a single device pass. This study assessed the health benefit and economic impact of achieving FPE for acute ischaemic stroke (AIS) patients from the Spanish National Health System (NHS) perspective. DESIGN: A lifetime Markov model was used to estimate incremental costs and health outcomes (measured in quality-adjusted life-years (QALYs)) of patients that achieve FPE. A subanalysis of the Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischaemic Stroke (STRATIS) registry was performed to obtain clinical outcomes. The base case included all patients that achieved at least a final mTICI ≥2 b, while the alternative scenario included all patients regardless of their final mTICI (0-3). Treatment costs were updated to reflect current practice based on expert panel consensus, while other acute and long-term costs were obtained from a previous cost-effectiveness analysis of MT performed in Spain. Sensitivity analyses were performed to assess the model's robustness. SETTING: Spanish healthcare perspective. PARTICIPANTS: AIS patients in Spain. INTERVENTIONS: FPE following MT. OUTCOME MEASURES: The model estimated QALYs, lifetime costs and net monetary benefit for the FPE and non-FPE group, depending on the inclusion of reperfusion groups and formal care costs. RESULTS: STRATIS subanalysis estimated significantly better clinical outcomes at 90 days for the FPE group in all scenarios. In the base case, the model estimated lifetime cost saving per patient of €16 583 and an incremental QALY gain of 1.2 years of perfect health for the FPE group. Cost savings and QALY gains were greater in the alternative scenario (-€44 289; 1.75). In all scenarios, cost savings were driven by the long-term cost reduction. CONCLUSION: Achieving FPE after MT can lead to better health outcomes per AIS patient and important cost savings for the Spanish NHS.

First Pass Effect With Neurothrombectomy for Acute Ischemic Stroke: Analysis of the Systematic Evaluation of Patients Treated With Stroke Devices for Acute Ischemic Stroke Registry.

BACKGROUND AND PURPOSE: Achieving complete revascularization after a single pass of a mechanical thrombectomy device (first pass effect [FPE]) is associated with good clinical outcomes in patients with acute ischemic stroke due to large vessel occlusion. We assessed patient characteristics, outcomes, and predictors of FPE among a large real-world cohort of patients (Systematic Evaluation of Patients Treated with Stroke Devices for Acute Ischemic Stroke registry). METHODS: Demographics, clinical outcomes, and procedural characteristics were analyzed among patients in whom FPE (modified Thrombolysis in Cerebral Infarction 2c/3 after first pass) was achieved versus those requiring multiple passes (MP). Modified FPE and modified MP included patients achieving modified Thrombolysis in Cerebral Infarction 2B-3. Primary outcomes included 90-day modified Rankin Scale (mRS) score and mortality. RESULTS: Among 984 Systematic Evaluation of Patients Treated with Stroke Devices for Acute Ischemic Stroke patients, 930 had complete 90-day follow-up. FPE was achieved in 40.5% (377/930) of patients and MP in 20.0% (186/930). Baseline characteristics were similar across all groups. The FPE group had fewer internal carotid artery occlusions compared with MP (P=0.029). The FPE group had faster puncture to recanalization time (P≤0.001), higher rates of 90-day mRS score of 0 to 1 (52.6% versus 38.6%, P=0.003), mRS score of 0 to 2 (65.4% versus 52.0%, P=0.003), and lower 90-day mortality compared with the MP group (12.0% versus 18.7%, P=0.038). Similarly, compared with modified MP patients, the modified FPE group had fewer internal carotid artery occlusions (P=0.004), faster puncture to recanalization time (P≤0.001), and higher rates of 90-day mRS score of 0 to 1 (P=0.002) and mRS score of 0 to 2 (P=0.003). CONCLUSIONS: Our findings demonstrate that FPE and modified FPE are associated with superior clinical outcomes.

Stent Retriever Thrombectomy for Anterior vs. Posterior Circulation Ischemic Stroke: Analysis of the STRATIS Registry.

Background and Purpose: The benefits of mechanical thrombectomy (MT) in vertebrobasilar artery occlusions have not been well-studied. We compared clinical, procedural, and safety outcomes of MT for posterior circulation (PC) vs. anterior circulation (AC) occlusions among patients in the STRATIS registry. Methods: Data from STRATIS including patient demographics, procedural characteristics, and outcomes including symptomatic intracranial hemorrhage (sICH) at 24 h, serious adverse events (SAE), substantial reperfusion [modified thrombolysis in cerebral infarction (mTICI) 2b/3], 90-day functional independence [modified Rankin Scale (mRS) 0-2], and 90-day mortality were analyzed. Univariate logistic regression was used to calculate predictors of good clinical outcome. Results: Of 984 STRATIS patients, 43 (4.4%) patients with PC occlusions [mean age 63.0 ± 13.6, 25.6% (11/43) female] and 932 (94.7%) with AC occlusions [mean age 68.5 ± 14.8, 46.9% (437/932) female] were included for analysis. Median National Institutes of Health Stroke Scale (NIHSS) scores at baseline were 17.0 (13.0, 12.0) for the AC group and 12.0 (11.0, 24.0) for the PC group. Time from onset to procedure end was longer for the PC group [median (IQR): 322.0 min (255.0-421.0) vs. 271.0 min (207.0-360.0); p = 0.007]. PC and AC groups had similar rates of substantial reperfusion [89.2% (33/37) vs. 87.7% (684/780)], procedure-related SAE [0.0% (0/43) vs. 1.7% (16/932)], sICH [0.0% (0/38) vs. 1.5% (12/795)], 90-day functional independence [66.7% (26/39) vs. 55.9% (480/858)] and mortality [12.8% (5/39) vs. 15.8% (136/861)]. National Institutes of Health Stroke Scale score and patient sex were significant univariate predictors of good clinical outcome (p < 0.05). Conclusions: Despite longer reperfusion times, MT in PC stroke has similar rates of 90-day functional independence with no significant difference in procedure-related SAE, sICH, or mortality, supporting the use of MT in PC acute ischemic stroke (AIS). Clinical Trial Registration:https://www.clinicaltrials.gov, Identifier: NCT02239640.

Middle Cerebral Artery M2 Thrombectomy in the STRATIS Registry.

Background and Purpose: The safety and benefit of mechanical thrombectomy in the treatment of acute ischemic stroke patients with M2 segment middle cerebral artery occlusions remain uncertain. Here, we compare clinical and angiographic outcomes in M2 versus M1 occlusions in the STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) Registry. Methods: The STRATIS Registry was a prospective, multicenter, nonrandomized, observational study of acute ischemic stroke large vessel occlusion patients treated with the Solitaire stent-retriever as the first-choice therapy within 8 hours from symptoms onset. Primary outcome was defined as functional disability at 3 months measured by dichotomized modified Rankin Scale. Secondary outcomes included reperfusion rates and rates of symptomatic intracranial hemorrhage. Results: A total of 984 patients were included, of which 538 (54.7%) had M1 and 170 (17.3%) had M2 occlusions. Baseline demographics were well balanced within the groups, with the exception of mean baseline National Institutes of Health Stroke Scale score which was significantly higher in the M1 population (17.3±5.5 versus 15.7±5.0, P≤0.001). No difference was seen in mean puncture to revascularization times between the cohorts (46.0±27.8 versus 45.1±29.5 minutes, P=0.75). Rates of successful reperfusion (modified Thrombolysis in Cerebral Infarction≥2b) were similar between the groups (91% versus 95%, P=0.09). M2 patients had significantly increased rates of symptomatic ICH at 24 hours (4% versus 1%, P=0.01). Rates of good functional outcome (modified Rankin Scale score of 0­2; 58% versus 59%, P=0.83) and mortality (15% versus 14%, P=0.75) were similar between the 2 groups. There was no difference in the association of outcome and onset to groin puncture or onset to successful reperfusion in M1 and M2 occlusions. Conclusions: In the STRATIS Registry, M2 occlusions achieved similar rates of successful reperfusion, good functional outcome, and mortality, although increased rates of symptomatic ICH were demonstrated when compared with M1 occlusions. The time dependence of benefit was also similar between the 2 groups. Further studies are needed to understand the benefit of mechanical thrombectomy for M2 occlusions. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239640.

Subarachnoid Hemorrhage in Mechanical Thrombectomy for Acute Ischemic Stroke: Analysis of the STRATIS Registry, Systematic Review, and Meta-Analysis.

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.

Impact of Age and Alberta Stroke Program Early Computed Tomography Score 0 to 5 on Mechanical Thrombectomy Outcomes: Analysis From the STRATIS Registry.

BACKGROUND AND PURPOSE: This study investigates clinical outcomes after mechanical thrombectomy in adult patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) of 0 to 5. METHODS: We included data from the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) from patients who underwent mechanical thrombectomy within 8 hours of symptom onset and had available ASPECTS data adjudicated by an independent core laboratory. Angiographic and clinical outcomes were collected, including successful reperfusion (modified Thrombolysis in Cerebral Infarction ≥2b), functional independence (modified Rankin Scale score 0-2), 90-day mortality, and symptomatic intracranial hemorrhage at 24 hours. Outcomes were stratified by ASPECTS scores and age. RESULTS: Of the 984 patients enrolled, 763 had available ASPECTS data. Of these patients, 57 had ASPECTS of 0 to 5 with a median age of 63 years (interquartile range, 28-100), whereas 706 patients had ASPECTS of 6 to 10 with a median age of 70 years of age (interquartile range, 19-100). Ten patients had ASPECTS of 0 to 3 and 47 patients had ASPECTS of 4 to 5 at baseline. Successful reperfusion was achieved in 85.5% (47/55) in the ASPECTS of 0 to 5 group. Functional independence was achieved in 28.8% (15/52) in the ASPECTS of 0 to 5 versus 59.7% (388/650) in the 6 to 10 group (P<0.001). Mortality rates were 30.8% (16/52) in the ASPECTS of 0 to 5 and 13.4% (87/650) in the 6 to 10 group (P<0.001). sICH rates were 7.0% (4/57) in the ASPECTS of 0 to 5 and 0.9% (6/682) in the 6 to 10 group (P<0.001). No patients aged >75 years with ASPECTS of 0 to 5 (0/12) achieved functional independence versus 44.8% (13/29) of those age ≤65 (P=0.005). CONCLUSIONS: Patients <65 years of age with large core infarction (ASPECTS 0-5) have better rates of functional independence and lower rates of mortality compared with patients >75 years of age. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239640.

New Class of Radially Adjustable Stentrievers for Acute Ischemic Stroke: Primary Results of the Multicenter TIGER Trial.

[Figure: see text].

Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: a systematic review and meta-analysis of observational data.

BACKGROUND: Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse. METHODS: We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin Scale ≤2, mortality at 90 days). RESULTS: The search identified six observational cohort studies and three observational datasets of MT randomized-controlled trial data reporting on IA fibrinolytics with MT as compared with MT alone, including 2797 patients (405 with additional IA fibrinolytics (100 urokinase (uPA), 305 tissue plasminogen activator (tPA)) and 2392 patients without IA fibrinolytics). Of 405 MT patients treated with additional IA fibrinolytics, 209 (51.6%) received prior intravenous tPA. We did not observe an increased risk of sICH after administration of IA fibrinolytics as adjunct to MT (OR 1.06, 95% CI 0.64 to 1.76), nor excess mortality (0.81, 95% CI 0.60 to 1.08). Although the mode of reporting was heterogeneous, some studies observed improved reperfusion after IA fibrinolytics. CONCLUSION: The quality of evidence regarding peri-interventional administration of IA fibrinolytics in MT is low and limited to observational data. In highly selected patients, no increase in sICH was observed, but there is large uncertainty.

Impact of EMS bypass to endovascular capable hospitals: geospatial modeling analysis of the US STRATIS registry.

BACKGROUND: Routing patients directly to endovascular capable centers (ECCs) would decrease time to mechanical thrombectomy (MT), but may delay intravenous thrombolysis (IVT). OBJECTIVE: To study the clinical outcomes of patients with a stroke transferred directly to ECCs compared with those transferred to ECCs from non-endovascular capable centers (nECCs). METHODS: Data from the STRATIS registry were analyzed to evaluate process and clinical outcomes under five routing policies: (1) transport to nearest nECC; (2) transport to STRATIS ECC over any distance or (3) within 20 miles; (4) transport to ideal ECC (iECC), over any distance or (5) within 20 miles. RESULTS: Among 236 patients, 117 (49.6%) were transferred by ground, of whom 62 (53%) were transferred within 20 miles. Median MT start time was accelerated in all direct transport models. IVT start was prolonged with direct transport across all distances, but accelerated with direct transport to iECC ≤20 miles. With bypass limited to ≤20 miles, the median modeled EMS arrival to IVT interval decreased for both iECCs and ECCs (by 12 min and 6 min, respectively), and median EMS arrival to puncture time decreased by up to 94 min. In this cohort, no patient would have become ineligible for IVT. Bypass to iECC modeling under 20 miles showed a significant reduction in the level of disability at 3 months, with freedom from disability (modified Rankin Scale score 0-1) at 3 months increased by 12%. CONCLUSIONS: Direct routing of patients with a large vessel occlusion to ECCs, especially when within 20 miles, may lead to better clinical outcomes by accelerating the start of MT without any delay of IVT. CLINICAL TRIAL REGISTRATION NUMBER: http://www.clinicaltrials.gov. Unique identifier: NCT02239640.

Patterns and Outcomes of Endovascular Therapy in Mild Stroke.

Background and Purpose- We aimed to evaluate the current practice patterns, safety and outcomes of patients who receive endovascular therapy (EVT) having mild neurological symptoms. Methods- From Jan 2010 to Jan 2018, 127,794 ischemic stroke patients were enrolled in the Florida-Puerto Rico Stroke Registry. Patients presenting within 24 hours of symptoms who received EVT were classified into mild (National Institutes of Health Stroke Scale [NIHSS] ≤5) or moderate/severe (NIHSS>5) categories. Differences in clinical characteristics and outcomes were evaluated using multivariable logistic regression. Results- Among 4110 EVT patients (median age, 73 [interquartile range=20] years; 50% women), 446 (11%) had NIHSS ≤5. Compared with NIHSS >5, those with NIHSS ≤5 arrived later to the hospital (median, 138 versus 101 minutes), were less likely to receive intravenous alteplase (30% versus 43%), had a longer door-to-puncture time (median, 167 versus 115 minutes) and more likely treated in South Florida (64% versus 53%). In multivariable analysis younger age, private insurance (versus Medicare), history of hypertension, prior independent ambulation and hospital size were independent characteristics associated with NIHSS ≤5. Among EVT patients with NIHSS ≤5, 76% were discharged home/rehabilitation and 64% were able to ambulate independently at discharge as compared with 53% and 32% of patients with NIHSS >5. Symptomatic intracerebral hemorrhage occurred in 4% of mild stroke EVT patients and 6.4% in those with NIHSS >5. Conclusions- Despite lack of evidence-based recommendations, 11% of patients receiving EVT in clinical practice have mild neurological presentations. Individual, hospital and geographic disparities are observed among endovascularly treated patients based on the severity of clinical symptoms. Our data suggest safety and overall favorable outcomes for EVT patients with mild stroke.

Intraarterial Thrombolysis as Rescue Therapy for Large Vessel Occlusions.

Background and Purpose- Mechanical thrombectomy (MT) devices have led to improved reperfusion and clinical outcomes in acute ischemic stroke patients with emergent large vessel occlusions; however, less than one-third of patients achieve complete reperfusion. Use of intraarterial thrombolysis in the context of MT may provide an opportunity to enhance these results. Here, we evaluate the use of intraarterial rtPA (recombinant tissue-type plasminogen activator) as rescue therapy (RT) after failed MT in the North American Solitaire Stent-Retriever Acute Stroke registry. Methods- The North American Solitaire Stent-Retriever Acute Stroke registry recruited sites within North America to submit data on acute ischemic stroke patients treated with the Solitaire device. After restricting the population of 354 patients to use of RT and anterior emergent large vessel occlusions, we compared patients who were treated with and without intraarterial rtPA after failed MT. Results- A total of 37 and 44 patients was in the intraarterial rtPA RT and the no intraarterial rtPA RT groups, respectively. Revascularization success (modified Thrombolysis in Cerebral Infarction ≥2b) was achieved in more intraarterial rtPA RT patients (61.2% versus 46.6%; P=0.13) with faster times to recanalization (100±85 versus 164±235 minutes; P=0.36) but was not statistically significant. The rate of symptomatic intracranial hemorrhage (13.9% versus 6.8%; P=0.29) and mortality (42.9% versus 44.7%; P=0.87) were similar between the groups. Good functional outcome (modified Rankin Scale score of ≤2) was numerically higher in intraarterial rtPA patients (22.9% versus 18.4%; P=0.64). Further restriction of the RT population to M1 occlusions only and time of onset to groin puncture ≤8 hours, resulted in significantly higher successful revascularization rates in the intraarterial rtPA RT cohort (77.8% versus 38.9%; P=0.02). Conclusions- Intraarterial rtPA as RT demonstrated a similar safety and clinical outcome profile, with higher reperfusion rates achieved in patients with M1 occlusions. Prospective studies are needed to delineate the role of intraarterial thrombolysis in MT.

Impact of Balloon Guide Catheter Use on Clinical and Angiographic Outcomes in the STRATIS Stroke Thrombectomy Registry.

Background and Purpose- Mechanical thrombectomy has been shown to improve clinical outcomes in patients with acute ischemic stroke. However, the impact of balloon guide catheter (BGC) use is not well established. Methods- STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter study of patients with large vessel occlusion treated with the Solitaire stent retriever as first-line therapy. In this study, an independent core laboratory, blinded to the clinical outcomes, reviewed all procedures and angiographic data to classify procedural technique, target clot location, recanalization after each pass, and determine the number of stent retriever passes. The primary clinical end point was functional independence (modified Rankin Scale, 0-2) at 3 months as determined on-site, and the angiographic end point was first-pass effect (FPE) success rate from a single device attempt (modified Thrombolysis in Cerebral Infarction, ≥2c) as determined by a core laboratory. Achieving modified FPE (modified Thrombolysis in Cerebral Infarction, ≥2b) was also assessed. Comparisons of clinical outcomes were made between groups and adjusted for baseline and procedural characteristics. All participating centers received institutional review board approval from their respective institutions. Results- Adjunctive technique groups included BGC (n=445), distal access catheter (n=238), and conventional guide catheter (n=62). The BGC group had a higher rate of FPE following first pass (212/443 [48%]) versus conventional guide catheter (16/62 [26%]; P=0.001) and distal access catheter (83/235 [35%]; P=0.002). Similarly, the BGC group had a higher rate of modified FPE (294/443 [66%]) versus conventional guide catheter (26/62 [42%]; P<0.001) and distal access catheter (129/234 [55%]; P=0.003). The BGC group achieved the highest rate of functional independence (253/415 [61%]) versus conventional guide catheter (23/55 [42%]; P=0.007) and distal access catheter (113/218 [52%]; P=0.027). Final revascularization and mortality rates did not differ across the groups. Conclusions- BGC use was an independent predictor of FPE, modified FPE, and functional independence, suggesting that its routine use may improve the rates of early revascularization success and good clinical outcomes. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

Impact of Stent Retriever Size on Clinical and Angiographic Outcomes in the STRATIS Stroke Thrombectomy Registry.

Background and Purpose- The safety and efficacy of mechanical thrombectomy in patients with acute ischemic stroke has been demonstrated. However, the impact of stent retriever size on clinical and angiographic outcomes is not well established. Methods- This was a retrospective ad hoc analysis of data from the STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) registry-a prospective, multicenter study of patients with large vessel occlusion treated with the Solitaire stent retriever. An independent core laboratory, blinded to clinical outcomes, reviewed all procedures and angiographic data to classify stent retriever size, targeted clot location, recanalization after each pass, and the number of stent retriever passes. The primary angiographic end point was first-pass effect (FPE) as determined by a core laboratory and defined as achieving near-complete revascularization (modified Thrombolysis in Cerebral Infarction ≥2c) after the first pass without the use of rescue therapy. Rates of modified FPE were also assessed, defined as meeting all criteria for FPE but achieving modified Thrombolysis in Cerebral Infarction ≥2b after first pass. The primary clinical end point was functional independence (modified Rankin Scale, 0-2) at 3 months as determined on-site. Outcome comparisons were made across the stent retriever size groups and adjusted for baseline characteristics. Results- Of 715 patients, a 4×20 stent retriever was used in 201 (28%) patients, 4×40 was used in 270 (38%) patients, and 6×30 was used in 244 (34%) patients. The 4×40 group had the highest rate of FPE ( P=0.003 versus 6×30) and modified FPE ( P=0.038 versus 4×20; P=0.0001 versus 6×30). Final revascularization was not significantly different across the groups, and there were no significant differences in functional dependence or mortality at 90 days post-procedure. Use of the longer stent retriever (4×40) was an independent predictor of achieving modified FPE ( P=0.037 versus 6×30; P=0.037 versus 4×20). Conclusions- The longer stent retriever (4×40) demonstrated the highest rate FPE and modified FPE compared with larger diameter or shorter stent retrievers, suggesting that their routine use may improve early revascularization success. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

Real-world stent retriever thrombectomy for acute ischemic stroke beyond 6 hours of onset: analysis of the NASA and TRACK registries.

BACKGROUND: The DEFUSE 3 and DAWN trials have shown the benefit of thrombectomy beyond 6 hours of stroke symptom onset in carefully selected patients. OBJECTIVE: To evaluate the real-world outcomes of stent retriever thrombectomy beyond 6 hours of stroke onset using combined individual patient data from the North American Solitaire Stent Retriever Acute Stroke (NASA) and Trevo Stent-Retriever Acute Stroke (TRACK) registries. METHODS: Pooled analysis of individual patient data of all cases of anterior circulation acute ischemic stroke (AIS) from NASA and TRACK was performed to compare outcomes of patients presenting within the first hours 6 or beyond 6 hours of stroke symptom onset. RESULTS: Of 830 patients with anterior circulation AIS from the NASA and TRACK registries, 32.7% (271 patients) underwent thrombectomy beyond the first 6 hours of symptom onset. The rates of good clinical outcome (modified Rankin scale score of 0-2 at 90 days), mortality, and symptomatic intracranial hemorrhage were similar: 48.1%, 20.6%, and 8.0% within 0-6 hours, 46.2%, 21.6%, and 10.9% within 6-16 hours, and 38.9%, 33.3%, and 5% within 16-24 hours (p=0.8, 0.6, and 0.5, respectively). The rates of successful recanalization (Thrombolysis in Cerebral Infarction 2b/3) were 79.4% in patients with stroke within 0-6 hours, 72.6% within 6-16 hours, and 85.0% within 16-24 hours (p=0.04). CONCLUSIONS: Real-world experience with patients with anterior circulation AIS treated with the Solitaire and Trevo thrombectomy devices beyond the first 6 hours of symptom onset proved to be equally safe and effective as for patients with symptom onset within the first 6 hours.