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.

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.

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.

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.

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.

Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke: Primary Results of the STRATIS Registry.

BACKGROUND AND PURPOSE: Mechanical thrombectomy with stent retrievers has become standard of care for treatment of acute ischemic stroke patients because of large vessel occlusion. The STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) aimed to assess whether similar process timelines, technical, and functional outcomes could be achieved in a large real world cohort as in the randomized trials. METHODS: STRATIS was designed to prospectively enroll patients treated in the United States with a Solitaire Revascularization Device and Mindframe Capture Low Profile Revascularization Device within 8 hours from symptom onset. The STRATIS cohort was compared with the interventional cohort of a previously published SEER patient-level meta-analysis. RESULTS: A total of 984 patients treated at 55 sites were analyzed. The mean National Institutes of Health Stroke Scale score was 17.3. Intravenous tissue-type plasminogen activator was administered in 64.0%. The median time from onset to arrival in the enrolling hospital, door to puncture, and puncture to reperfusion were 138, 72, and 36 minutes, respectively. The Core lab-adjudicated modified Thrombolysis in Cerebral Infarction ≥2b was achieved in 87.9% of patients. At 90 days, 56.5% achieved a modified Rankin Scale score of 0 to 2, all-cause mortality was 14.4%, and 1.4% suffered a symptomatic intracranial hemorrhage. The median time from emergency medical services scene arrival to puncture was 152 minutes, and each hour delay in this interval was associated with a 5.5% absolute decline in the likelihood of achieving modified Rankin Scale score 0 to 2. CONCLUSIONS: This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02239640.

Complete reperfusion mitigates influence of treatment time on outcomes after acute stroke.

BACKGROUND: Time to reperfusion following endovascular treatment (ET) predicts outcomes after acute ischemic stroke (AIS). OBJECTIVE: To assess the time-outcome relationship within reperfusion grades in the North American Solitaire Acute Stroke registry. METHODS: We identified patients given ET for anterior circulation ischemic stroke within 8 h from onset and in whom reperfusion was achieved. Together with clinical and outcome data, site-adjudicated modified Thrombolysis in Cerebral Ischemia (TICI) was recorded. We assessed the impact of time to reperfusion (onset to procedure completion time) on good outcome (modified Rankin Scale 0-2 at 3 months) in patients who achieved TICI 2 or higher reperfusion in multivariable models. We further assessed this relationship within strata of reperfusion grades. A p<0.05 was considered significant. RESULTS: Independent predictors of good outcome at 3 months among those achieving TICI ≥2a reperfusion (n=188) were initial National Institutes of Health Stroke Scale score (adjusted OR=0.90, 95% CI 0.85 to 0.95), symptomatic hemorrhage (adj. OR=0.16, 95% CI 0.05 to 0.60), TICI grade (TICI 3: adj. OR=11.52, 95% CI 3.34 to 39.77; TICI 2b: adj. OR=5.14, 95% CI 1.61 to 16.39), and time to reperfusion per 30 min interval (adj. OR=0.91, 95% CI 0.82 to 0.99). There was an interaction between final TICI grade and 30 min time to reperfusion intervals (p=0.001) such that the effect of time was strongest in TICI 2a patients. CONCLUSIONS: Time to reperfusion was a strong predictor of outcome following ET for AIS. However, the effect varied by TICI grade such that its greatest effect was in those achieving TICI 2a reperfusion.