Intra-arterial tenecteplase after successful endovascular therapy (ANGEL-TNK): protocol of a multicentre, open-label, blinded end-point, prospective, randomised trial.

BACKGROUND: Despite successful reperfusion after thrombectomy for large vessel occlusion (LVO) stroke, up to half of patients are dependent or dead at 3-month follow-up.The aim of the current study is to demonstrate safety and efficacy of administering adjunct intra-arterial (IA) tenecteplase in anterior circulation LVO patients who have achieved successful reperfusion defined as eTICI 2b50 to 3. METHODS: ANGEL-TNK is a multicentre, open-label, assessor-blinded endpoint, prospective randomised, controlled trial that will enrol up to 256 patients. Patients who meet inclusion criteria with anterior circulation LVO stroke and successful reperfusion will be randomised to receive IA tenecteplase or best medical management at 1:1 ratio. RESULTS: The primary endpoint is a 90-day excellent outcome defined as modified Rankin Scale (mRS) 0-1. The primary safety endpoint is symptomatic intracranial haemorrhage within 48 hours from randomisation. Secondary endpoints include 90-day ordinal mRS, mRS 0-2, mRS 0-3, all-cause mortality and any intracranial haemorrhage. CONCLUSION: In patients with anterior circulation LVO stroke, the ANGEL-TNK trial will inform whether adjunct IA tenecteplase administered after successful thrombectomy reperfusion improves patient outcomes. TRIAL REGISTRATION NUMBER: NCT05624190.

Diagnostic accuracy of hemodynamic assessment of intracranial atherosclerotic stenosis from a single angiographic view: a validation study.

BACKGROUND: The aim of this study is to assess the feasibility of identifying the hemodynamic status of intracranial atherosclerotic stenosis (ICAS) using angio-based fractional flow (FF) calculated from a single angiographic view, with wire-based FF as the reference standard. METHOD: The study retrospectively recruited 100 ICAS patients who underwent pressure wire measurement and digital subtraction angiography. The AccuICAD software was used to calculate angio-based FF, with the wire-measured value serving as the reference standard for evaluating the accuracy, consistency, and diagnostic performance of angio-based FF. RESULTS: The mean±SD value of wire-based FF was 0.77±0.18, while the mean value of angio-based FF was 0.77±0.19. A good correlation between angio-based FF and wire-based FF was evident (r=0.90, P<0.001), with good agreement (mean difference 0.00±0.08). The diagnostic accuracy of angio-based FF and percent diameter stenosis (DS%) were 93.23% versus 72.18%, 91.73% versus 72.93%, and 89.47% versus 78.95% for predicted wire-based FF thresholds of 0.70, 0.75, and 0.80, respectively. The area under the curve (AUC) values for angio-based FF and DS% were 0.975 versus 0.822, 0.970 versus 0.814, and 0.943 versus 0.826 at the respective thresholds, respectively. CONCLUSION: The FF calculated from a single angiographic view can be considered an effective tool for functional assessment of cerebral arterial stenosis.

Development and Validation of a Two-step Model to Predict Outcomes After Endovascular Treatment for Patients With Acute Ischemic Stroke.

BACKGROUND: Physicians and patients are eager to know likely functional outcomes at different stages of treatment after acute ischemic stroke (AIS). The aim of this study was to develop and validate a 2-step model to assess prognosis at different time points (pre- and posttreatment) in patients with AIS having endovascular thrombectomy (EVT). METHODS: The prediction model was developed using a prospective nationwide Chinese registry (ANGEL-ACT). A total of 1676 patients with AIS who underwent EVT were enrolled into the study and randomly divided into development (n=1351, 80%) and validation (n=325, 20%) cohorts. Multivariate logistic regression, least absolute shrinkage and selection operator regression, and the random forest recursive feature elimination algorithm were used to select predictors of 90-day functional independence. We constructed the model via discrimination, calibration, decision curve analysis, and feature importance. RESULTS: The incidence of 90-day functional independence was 46.3% and 40.6% in the development and validation cohorts, respectively. The area under the curve (AUC) for model 1 which included 5 pretreatment predictors (age, admission National Institutes for Health Stroke Scale score, admission glucose level, admission systolic blood pressure, and Alberta Stroke Program Early Computed Tomography score) was 0.699 (95% confidence interval [CI], 0.668-0.730) in the development cohort and 0.658 (95% CI, 0.592-0.723) in the validation cohort. Two treatment-related predictors (time from stroke onset to puncture and successful reperfusion) were added to model 2 which had an AUC of 0.719 (95% CI, 0.688-0.749) and 0.650 (95% CI, 0.585-0.716) in the development cohort and validation cohorts, respectively. CONCLUSIONS: The 2-step prediction model could be useful for predicting the functional independence in patients with AIS 90-days after EVT.

Spontaneous recanalization in acute large core ischemic stroke due to large vessel occlusion: a post-hoc analysis of the ANGEL-ASPECT trial.

BACKGROUND: Previous studies have indicated that a subset of patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) experience spontaneous recanalization (SR), but the prognosis and factors associated with SR in these individuals are not well characterized. METHODS: We conducted a post hoc secondary analysis of the Study of Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core (ANGEL-ASPECT) trial. SR in the medical management group was defined as a modified arterial occlusive lesion (AOL) grade of 2 or 3 on computed tomography angiography (CTA) or magnetic resonance angiography (MRA) at 36 hours (±12 hours). RESULTS: SR was detected in 67 out of 184 patients (36.4%) in the medical management (MM) group. The median age of patients was 67 years (interquartile range (IQR) 58-72), and 48 (71.6%) were male. The adjusted odds ratio (aOR) for 90-day modified Rankin Scale (mRS) score shift toward better outcomes of the MM with SR group vs the MM without SR group was 1.83, with marginally significant difference (95% confidence interval (CI) 0.992 to 3.36; P=0.053). No significant difference was found between the MM with SR group and EVT recanalization group (aOR 1.45; 95% CI 0.86 to 2.43; P=0.16) with similar findings in the inverse probability treatment weighting analysis (OR 0.85; 95% CI 0.49 to 1.48; P=0.57). Multivariable regression analysis showed that hypertension, atherothrombotic stroke and higher clot burden score were factors associated with SR. CONCLUSIONS: SR in medically managed patients with acute large ischemic stroke caused by LVO was associated with good functional outcome. An improved understanding of SR patients may be helpful to develop therapeutic strategy in patients with large infarct due to LVO in anterior circulation. TRIAL REGISTRATION NUMBER: NCT04551664.

Balloon Angioplasty vs Medical Management for Intracranial Artery Stenosis: The BASIS Randomized Clinical Trial.

Importance: Previous randomized clinical trials did not demonstrate the superiority of endovascular stenting over aggressive medical management for patients with symptomatic intracranial atherosclerotic stenosis (sICAS). However, balloon angioplasty has not been investigated in a randomized clinical trial. Objective: To determine whether balloon angioplasty plus aggressive medical management is superior to aggressive medical management alone for patients with sICAS. Design, Setting, and Participants: A randomized, open-label, blinded end point clinical trial at 31 centers across China. Eligible patients aged 35 to 80 years with sICAS defined as recent transient ischemic attack (<90 days) or ischemic stroke (14-90 days) before enrollment attributed to a 70% to 99% atherosclerotic stenosis of a major intracranial artery receiving treatment with at least 1 antithrombotic drug and/or standard risk factor management were recruited between November 8, 2018, and April 2, 2022 (final follow-up: April 3, 2023). Interventions: Submaximal balloon angioplasty plus aggressive medical management (n = 249) or aggressive medical management alone (n = 252). Aggressive medical management included dual antiplatelet therapy for the first 90 days and risk factor control. Main Outcomes and Measures: The primary outcome was a composite of any stroke or death within 30 days after enrollment or after balloon angioplasty of the qualifying lesion or any ischemic stroke in the qualifying artery territory or revascularization of the qualifying artery after 30 days through 12 months after enrollment. Results: Among 512 randomized patients, 501 were confirmed eligible (mean age, 58.0 years; 158 [31.5%] women) and completed the trial. The incidence of the primary outcome was lower in the balloon angioplasty group than the medical management group (4.4% vs 13.5%; hazard ratio, 0.32 [95% CI, 0.16-0.63]; P < .001). The respective rates of any stroke or all-cause death within 30 days were 3.2% and 1.6%. Beyond 30 days through 1 year after enrollment, the rates of any ischemic stroke in the qualifying artery territory were 0.4% and 7.5%, respectively, and revascularization of the qualifying artery occurred in 1.2% and 8.3%, respectively. The rate of symptomatic intracranial hemorrhage in the balloon angioplasty and medical management groups was 1.2% and 0.4%, respectively. In the balloon angioplasty group, procedural complications occurred in 17.4% of patients and arterial dissection occurred in 14.5% of patients. Conclusions and Relevance: In patients with sICAS, balloon angioplasty plus aggressive medical management, compared with aggressive medical management alone, statistically significantly lowered the risk of a composite outcome of any stroke or death within 30 days or an ischemic stroke or revascularization of the qualifying artery after 30 days through 12 months. The findings suggest that balloon angioplasty plus aggressive medical management may be an effective treatment for sICAS, although the risk of stroke or death within 30 days of balloon angioplasty should be considered in clinical practice. Trial Registration: ClinicalTrials.gov Identifier: NCT03703635.

Endovascular management of acute stroke.

Stroke related to large vessel occlusion is a leading cause of disability and death worldwide. Advances in endovascular therapy to reopen occluded arteries have been shown to reduce patient disability and mortality. Expanded indications to treat patients with large vessel occlusion in the late window (>6 h from symptom onset), with basilar artery occlusion, and with large ischaemic core at presentation have enabled treatment of more patients with simplified imaging methods. Ongoing knowledge gaps include an understanding of which patients with large ischaemic infarct are more likely to benefit from endovascular therapy, the role of endovascular therapy in patients who present with low National Institutes of Health Stroke Scale scores or medium or distal vessel occlusion, and optimal management of patients with underlying intracranial atherosclerotic disease. As reperfusion can now be facilitated by intravenous thrombolysis, mechanical thrombectomy, or both, the development of cytoprotective or adjunctive drugs to slow infarct growth, enhance reperfusion, or decrease haemorrhagic risk has gained renewed interest with the hope to improve patient outcomes.

Association of baseline blood pressure and outcomes in etiology subtypes of large vessel occlusion stroke: Data from ANGEL-ACT registry.

BACKGROUND: Blood pressure (BP) management at the initial stage of stroke caused by large-vessel occlusion (LVO) remains challenging. We assessed the association between baseline BP and clinical and safety outcomes of endovascular treatment (EVT) in different stroke etiologies. METHODS: Patients with acute ischemic stroke and anterior circulation LVO were screened from a prospective, multicenter registry of EVT from November 2017 to March 2019. The primary outcome was poor 90-day outcome (modified Rankin Scale score 3-6). The safety outcome was 24 h post-procedure parenchymal hematoma (PH). The Trial of Org 101072 in Acute Stroke Treatment criteria were used for etiologic stroke classification. Restricted cubic spline and binary logistic regression analysis were performed to examine the association between study outcomes and natural log-transformed BP. RESULTS: In subgroup analyses, a U-shaped correlation existed between baseline mean arterial pressure (MAP) and poor outcome in large-artery atherosclerosis stroke only. Higher MAP was an independent risk factor compared with a central reference value (≥ 133 mm Hg vs 96-115 mm Hg; adjusted OR [aOR], 2.50; 95 % CI, 1.09 to 5.71, P = 0.030). Whereas elevated MAP was associated with PH (aOR, 1.58; 95 % CI 1.04 to 2.39, P = 0.030 for a ln10-unit increase in natural log-transformed MAP) in the range <110 mm Hg exclusively for cardioembolic stroke. CONCLUSION: Whether it is cause or epiphenomenon, baseline BP was associated with 90-day outcome in large-artery atherosclerosis stroke, whereas in cardioembolic stroke baseline BP was correlated with post-procedure PH within a certain range. Identifying these features based on etiological subtypes may offer a reference for BP management in acute LVO stroke.

Pipeline embolization device placement under local versus general anesthesia: a propensity score-matched study.

OBJECTIVE: Pipeline embolization device (PED) placement for the treatment of intracranial aneurysms is safe and effective under general anesthesia (GA). However, GA is associated with certain risks, longer procedural time, and higher hospital cost. The authors aimed to compare clinical outcomes and hospital cost between GA and local anesthesia (LA) procedures in patients who underwent PED placement for intracranial aneurysm treatment. METHODS: This retrospective study analyzed the charts of 216 patients with 223 intracranial aneurysms treated using the PED from June 2022 to March 2023. Cases were grouped according to type of anesthesia administered (LA or GA). Propensity score matching (PSM) was used to balance the groups to minimize confounding bias. RESULTS: Eighty-four patients with 88 aneurysms were treated under LA, and 132 patients with 135 aneurysms were treated under GA. The complication rate and modified Rankin Scale score at 6 months were similar in both groups. Procedural time was significantly shorter with LA both before (87.47 ± 22.68 minutes vs 118.90 ± 46.80 minutes, p < 0.001) and after (84.75 ± 16.77 minutes vs 110.02 ± 38.56 minutes, p < 0.001) PSM. LA eliminates the need for postanesthesia recovery. Hospital cost was significantly lower in the LA group both before ($30,820.74 ± $3216.93 vs $32,846.62 ± $4731.50, p = 0.001) and after ($30,127.83 ± $2763.12 vs $33,874.41 ± $3163.56, p = 0.002) PSM. CONCLUSIONS: PED placement under LA can achieve satisfactory outcomes similar to those of PED placement under GA; however, the use of LA reduces procedural time and hospital cost.

Anaesthesia modality on endovascular therapy outcomes in patients with large infarcts: a post hoc analysis of the ANGEL-ASPECT trial.

OBJECTIVES: Endovascular therapy (EVT) now penetrates the once obscure realm of large infarct core volume acute ischaemic stroke (LICV-AIS). This research aimed to investigate the potential correlation between different anaesthetic approaches and post-EVT outcomes in LICV-AIS patients. METHODS: Between October 2020 and May 2022, the China ANGEL-Alberta Stroke Programme Early CT Score (ASPECT) trial studied patients with LICV-AIS, randomly assigning them to the best medical management (BMM) or BMM with EVT. This post hoc subgroup analysis categorised subjects receiving BMM with EVT into general anaesthesia (GA) and non-GA groups based on anaesthesia type. We applied multivariable logistic regression to evaluate the relationship between anaesthesia during EVT and patient functional outcomes, as measured by the modified Rankin scale (mRS), in addition to the occurrence of complications. Further adjustment for selection bias was achieved through propensity score matching (PSM). RESULTS: In total, 230 patients with LICV-AIS were enrolled (GA 84 vs Non-GA 146). No significant difference was observed between the two groups in terms of the proportion of patients who achieved an mRS score of 0-2 at 90 days (27.4% for the GA group vs 31.5% for the non-GA group, p=0.51). However, the GA group had significantly longer median surgical times (142 min vs 122 min, p=0.03). Furthermore, GA was associated with an increased risk of postoperative pneumonia (adjusted OR 2.03, 95% CI 1.04 to 3.98). The results of PSM analysis agreed with the results of the multivariate regression analysis. No significant difference in intracranial haemorrhage incidence or mortality rate was observed between the groups. CONCLUSION: This post hoc analysis of subgroups of the ANGEL-ASPECT trial suggested that there may be no significant association between the choice of anaesthesia and neurological outcomes in LICV-AIS patients. However, compared with non-GA, GA prolongs the duration of EVT and is associated with a greater postoperative pneumonia risk. TRIAL REGISTRATION NUMBER: NCT04551664.

Association of Mismatch Profiles and Clinical Outcome from Endovascular Therapy in Large Infarct: A Post-Hoc Analysis of the ANGEL-ASPECT Trial.

OBJECTIVES: We investigated whether patients with large infarct and the presence or absence of perfusion mismatch are associated with endovascular treatment benefit. METHODS: This is a post-hoc analysis of the Endovascular Therapy in Anterior Circulation Large Vessel Occlusion with a Large Infarct (ANGEL-ASPECT) randomized trial, which enrolled patients within 24 hours of onset with ASPECTS 3 to 5 or ASPECTS 0 to 2 with an infarct core 70 to 100 ml. Mismatch ratio was defined as time-to-maximum (Tmax) >6 s cerebral volume/ischemic core volume, and mismatch volume was defined as Tmax >6 s volume minus ischemic core volume. We divided patients into mismatch ratio ≥1.2 and mismatch volume ≥10 ml, and mismatch ratio ≥1.8 and mismatch volume ≥15 ml groups. The primary outcome was the 90-day modified Rankin Scale score ordinal distribution. Safety outcomes were symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: There were 425 patients included. In both the mismatch ratio ≥1.2 and mismatch volume ≥10 ml (mismatch+, n = 395; mismatch-, n = 31) and mismatch ratio ≥1.8 and mismatch volume ≥15 ml groups (mismatch+, n = 346; mismatch-, n = 80), better 90-day modified Rankin Scale outcomes were found in the endovascular treatment group compared with the MM group (4 [2-5] vs 4 [3-5], common odds ratio [cOR], 1.9, 95% confidence interval [CI] 1.3-2.7, p = 0.001; 4 [2-5] vs 4 [3-5], cOR, 1.9, 95% CI 1.3-2.8, p = 0.001, respectively), but not in patients without mismatch ratio ≥1.2 and mismatch volume ≥10 ml (5 [3-6] vs 5 [4-6], cOR, 1.2, 95% CI 0.3-4.1, p = 0.83), and mismatch ratio ≥1.8 and mismatch volume ≥15 ml (4 [3-6] vs 5 [3-6], cOR, 1.2, 95% CI 0.6-2.7, p = 0.60). However, no interaction effect was found in both subgroups (p interaction >0.10). CONCLUSION: Endovascular treatment was more efficacious than MM in patients with mismatch profiles, but no treatment effect or interaction was noted in the no mismatch profile patients. However, the small sample size of patients with no mismatch may have underpowered our analysis. A pooled analysis of large core trials stratified by mismatch is warranted. ANN NEUROL 2024.

Thrombectomy Plus Intra-Arterial Thrombolysis Versus Thrombectomy for Acute Large Vessel Occlusions: a Matched-Control Study.

AIM: We conducted a matched-control analysis to compare the outcomes of large vessel occlusion (LVO) patients treated with mechanical thrombectomy (MT) plus Intra-arterial thrombolysis (IAT) versus those treated with MT alone. METHODS: The subjects of this study were chosen from ANGEL-ACT registry. All patients who received MT were identified and categorized into two groups: "MT + IAT" and "MT," based on whether or not they received additional intra-arterial medication IAT during the MT procedure. After being subjected to 1:1 propensity score matching, the outcome measures, including modified Rankin Scale (mRS) score at 90 days, successful recanalization at the final angiogram, symptomatic intracranial hemorrhage (sICH) within 36 h, and death within 90 days, were compared. RESULTS: The study encompassed a total of 1607 patients, with 641 individuals assigned to the MT + IAT group and 966 to the MT group. After applying propensity score matching, a total of 524 pairs were identified for comparison. The results indicated that there were no significant differences between the two groups with regard to the modified Rankin Scale (mRS) score (median: 3 vs. 3 points; P = 0.83), successful recanalization (89.9 vs. 88.9%; P = 0.62), sICH (8.3 vs. 8.7%; P = 0.79), and death (15.5 vs. 16.4%; P = 0.70). CONCLUSIONS: IAT during MT does not confer an elevated risk of sICH or mortality. Furthermore, the combination of MT and IAT may produce comparable functional outcomes in comparison to MT alone, when treating acute LVO patients.

Comprehensive Assessment of Drug Kinetics, Neurotoxicity, and Safety of Sirolimus-Eluting Intracranial Stents in Canine Basilar Artery.

BACKGROUND AND OBJECTIVES: Sirolimus-eluting stents (SESs) have shown promise in treating intracranial atherosclerosis but concerns about potential neurotoxicity due to prolonged drug release exist. The aim of this study was to comprehensively assess the safety of SES, with a focus on neurotoxicity. METHODS: Stents (1.50 × 7 or 12 mm) were implanted into the basilar arteries of 154 Labrador Retrievers (weighing >25 kg and aged older than 1 year) divided into 4 groups: baer-metal stent, polymer-coated stent, standard-dose SES (sirolimus dose: 71 µg), and high-dose SES group (sirolimus dose: 284 µg). Pharmacokinetic analysis was conducted using liquid chromatography-mass spectrometry on blood and tissue samples, and analysis of brain tissue was performed with 5 different special stains and immunohistochemistry protocols to assess axonal degeneration, vacuolization, astrocyte proliferation, microglial activation, or widespread neurodegeneration. RESULTS: In the standard-dose SES group, the stent released 10.56% of the drug on day 1 and 95.41% on day 28 postimplantation. In the high-dose SES group, corresponding figures were 40.20% on day 1 and 98.08% on day 28. Systemic drug concentration consistently remained below 1.5 ng/mL throughout the study. Arterial tissue concentration reached its peak at day 28 days in the standard-dose group and at 7 days in the high-dose group. Importantly, the brain and related tissue concentrations remained below 0.4 µg/g in both standard-dose and high-dose SES groups, peaking on day 21 in the standard-dose group and day 1 in the high-dose group. The detailed 180-day safety assessment revealed no adverse effects on the brain, even at high sirolimus doses in the SES group. CONCLUSION: This study provides robust evidence supporting the long-term pharmacokinetic safety of SESs in the context of intracranial interventions for high-grade intracranial atherosclerosis. The results adequately alleviate concerns related to neurotoxicity and substantiate the feasibility of using these stents as a therapeutic choice in neurosurgery.

DRug-coated Balloon for Endovascular treatment of sYmptOmatic intracraNial stenotic Disease (DR. BEYOND): the protocol of a multicentre randomised trial.

BACKGROUND: Although endovascular stenting is considered an effective and safe therapeutic option for symptomatic intracranial atherosclerotic disease (sICAD), an elevated rate of restenosis remains an important issue for the conventional bare-metal stent (BMS). Recent evidence from observational studies suggests that applying drug-coated balloons (DCB) in sICAD may decrease restenosis occurrence. Additional large randomised studies are warranted to provide firmer evidence and to determine which patients would benefit most from DCB. AIM: To design a randomised trial to examine DCB angioplasty (Taijieweiye intracranial paclitaxel-coated balloon catheter) versus BMS stenting (Wingspan intracranial stent system) in patients with sICAD. DESIGN: This is a multicentre, prospective, randomised, open-label, blinded end-point study to assess whether DCB angioplasty reduces the risk of restenosis compared with BMS stenting in sICAD patients with high-grade stenosis (≥70%-99%). Our goal is to randomly assign 198 eligible individuals at a 1:1 ratio to undergo DCB angioplasty (intervention group) or BMS stenting (control group). OUTCOME: The primary efficacy outcome is restenosis at 6 months post treatment, that is, >50% stenosis in or within 5 mm of the treated segment and >20% absolute luminal loss. The primary safety outcome is stroke or death within 30 days post treatment. DISCUSSION: The DRug-coated Balloon for Endovascular treatment of sYmptOmatic intracraNial stenotic Disease trial aims to produce strong evidence on the efficacy and safety of DCB angioplasty as a promising therapeutic option for sICAD cases with high-grade stenosis.

Intracranial Aneurysms Managed by Parent Artery Reconstruction Using Tubridge Flow Diverter study: 1-year outcomes.

OBJECTIVE: Previous randomized controlled trials have reported a significantly higher occlusion rate of large and giant aneurysms when utilizing the Tubridge flow diverter (FD). In the present trial, the safety and efficacy of the Tubridge FD in treating unruptured internal carotid artery (ICA) or vertebral artery (VA) aneurysms were assessed in a real-world setting. METHODS: The Intracranial Aneurysms Managed by Parent Artery Reconstruction Using Tubridge Flow Diverter (IMPACT) study is a prospective, multicenter, single-arm clinical trial assessing the efficacy of the Tubridge FD in the management of unruptured aneurysms located in the ICA or VA. The primary endpoint was the complete occlusion (Raymond-Roy class 1) rate at the 1-year follow-up. The secondary endpoints included the technical success rate, the successful occlusion rate of the aneurysm, which is the degree of aneurysm embolization scored as Raymond-Roy class 1 or 2, major (> 50%) in-stent stenosis, and incidence of disabling stroke or neurological death associated with the target aneurysms. RESULTS: This study included 14 interventional neuroradiology centers, with 200 patients and 240 aneurysms. According to angiographic core laboratory assessment, 205 (85.4%) aneurysms were located in the ICA, 34 (14.2%) in the VA, and 1 (0.4%) in the middle cerebral artery. Additionally, 189 (78.8%) aneurysms were small (< 10 mm). At the 12-month follow-up, the total occlusion rate was 79.0% (166/210, 95% CI 72.91%-84.34%). Additionally, the occurrence of disabling stroke or neurological death related to the specified aneurysms was 1% (2/200). CONCLUSIONS: The 1-year results from the IMPACT trial affirm the safety record of use of the Tubridge FD in the treatment of intracranial aneurysms in real-world scenarios. These results reveal low morbidity and mortality rates of 3.5% and 1.5%, respectively. Furthermore, they provide evidence of the effectiveness of the Tubridge FD, as demonstrated by the complete occlusion achieved in 166 of 210 (79%) cases.

Semi-automatic computed tomography angiography quantification assessment is an alternative method to digital subtraction angiography in intracranial stenosis: a multicenter study.

Background: The recent randomized controlled trials studying intracranial atherosclerotic stenosis (ICAS) have used digital subtraction angiography (DSA) to quantify stenosis and enroll patients. However, some disadvantages of DSA such as invasive features, contrast agent overuse, and X-ray radiation overexposure, were not considered in these studies. This study aimed to explore whether computed tomography angiography (CTA) with semi-automatic analysis could be an alternative method to DSA in quantifying the absolute stenotic degree in clinical trials. Methods: Patients with 50-99% ICAS were consecutively screened, prospectively enrolled, and underwent CTA and DSA between March 2021 and December 2021 at 6 centers. This study was registered at www.chictr.org.cn (ChiCTR2100052925). The absolute stenotic degree of ICAS on CTA with semi-automatic analysis was calculated by several protocols using minimal/maximum/mean diameters of stenosis and reference site from a semi-automatic analysis software. Intraclass correlation coefficient (ICC) was used to evaluate the reliabilities of quantifying stenotic degree on CTA. The optimal protocol for quantifying ICAS on CTA was explored. The agreements of quantifying ICAS in calcified or non-calcified lesions and 50-69% or 70-99% stenosis on CTA and DSA were assessed. Results: A total of 191 participants (58.8±10.7 years; 148 men) with 202 lesions were enrolled. The optimal protocol for quantifying ICAS on CTA was calculated as (1 - the minimal diameter of stenosis/the mean diameter of reference) × 100% for its highest agreement with DSA [ICC, 0.955, 95% confidence interval (CI): 0.944-0.966, P<0.001]. Among the 202 lesions, 80.2% (162/202) exhibited severe stenosis on DSA. The accuracy of CTA in detecting severe ICAS was excellent (sensitivity =95.1%, positive predictive value =98.1%). The agreements between DSA and CTA in non-calcified lesions (ICC, 0.960 vs. 0.849) and severe stenosis (ICC, 0.918 vs. 0.841) were higher than those in calcified lesions and moderate stenosis. Conclusions: CTA with semi-automatic analysis demonstrated an excellent agreement with DSA in quantifying ICAS, making it promising to replace DSA for the measurement of absolute stenotic degree in clinical trials.

Impact of first pass effect in endovascular treatment of large core stroke: a post-hoc analysis of the ANGEL-ASPECT trial.

BACKGROUND: The first-pass effect (FPE) is linked to better safety and efficacy prognosis in patients with small- to- moderate sized ischemic infarctions. We evaluated the incidence, prognosis, and predictors of FPE in patients with large core infarctions (LCIs). METHODS: We conducted a post-hoc analysis of data from the Trial of Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core (ANGEL-ASPECT). The FPE was defined as a successful recanalization (expanded Thrombolysis in Cerebral Infarction (eTICI) 2 c/3, and eTICI 2b-3 as modified FPE (mFPE)) after one pass. The primary outcome was clinical functional independence, and the secondary outcomes were independent ambulation, assessed by the modified Rankin Scale (mRS) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) defined by the Heidelberg bleeding classification, any intracranial hemorrhage (ICH), and death within 90 days of stroke onset. RESULTS: Of the 226 patients in the study, FPE and mFPE were achieved in 33 (14.6%) and 82 (36.3%) patients, respectively. Patients with FPE exhibited shorter onset-to-puncture times (adjusted odds ratio [OR] 0.915; 95% confidence interval [CI]: 0.84 to 0.996), and patients with mFPE were older (OR 1.039; 95% CI: 1.005 to 1.075). mFPE was significantly associated with favorable outcomes (modified Rankin score [mRS] 0-2: OR 2.64; 95% CI: 1.37 to 5.07; mRS 0-3: OR 3.31; 95% CI: 1.73 to 6.33). FPE tended to improve outcomes (mRS 0-3: OR 2.24; 95% CI: 0.92 to 4.97; p=0.08). ICH rates (OR 0.60; 95% CI: 0.34 to 1.05; p=0.07) and 90-day deaths (OR 0.57; 95% CI: 0.30 to 1.09; p=0.09) tended to decrease in patients who achieved mFPE but not in patients who achieved FPE. CONCLUSIONS: In the ANGEL-ASPECT trial, patients who achieved mFPE had a higher rate of independent ambulation and functional independence, and the rates of any ICH and 90-day death tended to decrease.

Effectiveness and safety of bridging therapy and endovascular therapy in patients with large cerebral infarctions: from ANGEL-ASPECT.

BACKGROUND AND PURPOSE: The benefits of thrombolytic therapy before endovascular thrombectomy in cases of acute ischaemic stroke, with a large infarction volume, remain unclear. This analysis aims to evaluate the effectiveness and safety of bridging therapy and endovascular therapy among patients with large cerebral infarctions. METHODS: In this post-hoc analysis of the multicentre prospective study of ANGEL-ASPECT (Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core), participants were divided into two groups: an endovascular therapy group and a bridging therapy group. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. The primary safety outcome was symptomatic intracranial haemorrhage. Ordinal logistic regression was performed to compare the primary endpoint between the two groups. Subgroup analyses were conducted to further explore potential risk factors associated with the outcomes. RESULTS: 122 patients were included, of whom 77 (63%) underwent endovascular therapy and 45 (37%) underwent bridging therapy. The median scores on mRS at 90 days of the bridging therapy group and the endovascular therapy group were 3 (2-5) and 4 (2-6), with no significant differences (common OR 1.36; 95% CI 0.71 to 2.61). Symptomatic intracranial haemorrhage was reported in three patients who were in the endovascular and bridging therapy groups (relative risk (RR) 1.71; 95% CI 0.36 to 8.12). The mortality between two groups did not differ (RR 0.75; 95% CI 0.37 to 1.54). CONCLUSIONS: Our study indicated that endovascular therapy alone might be a viable option for patients with large cerebral infarctions, displaying no noticeable disparity in outcomes compared with bridging therapy.

Endovascular therapy in acute ischaemic stroke with large infarction with matched or mismatched clinical-radiological severities: a post-hoc analysis of the ANGEL-ASPECT trial.

Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3-5 or infarct core volume 70-100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18-2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06-2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].

Anesthesia on Clinical Outcomes in an Extended Time Window During Endovascular Stroke Therapy: Exploratory Analysis of the ANGEL-ACT Registry.

OBJECTIVE: Data on the impact of different anesthesia methods on clinical outcomes in patients with acute ischemic stroke undergoing endovascular therapy (EVT) in extended windows are limited. This study compared clinical outcomes in patients with stroke having general anesthesia (GA), conscious sedation (CS), or local anesthesia (LA) during EVT in extended (>6 h) time windows. METHODS: We conducted an exploratory analysis of data from the ANGEL-ACT registry. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included the proportions of patients with mRS scores of 0 to 1, 0 to 2, and 0 to 3, and safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH, or mortality within 90 days. Multivariate analyses, inverse probability of treatment weighting, and coarsened exact matching were used to adjust for indication bias. RESULTS: A total of 646 patients were included in the analysis (GA,280; CS, 103; LA, 263). Patients having LA during EVT were more likely to have a favorable mRS score (adjusted odds ratio [aOR]: 1.75; 95% CI: 1.28 to 2.40) and a lower incidence of symptomatic ICH (aOR: 0.33; 95% CI: 0.14 to 0.76) than those having GA group. Similarly, CS was associated with greater odds of favorable 90-day mRS scores compared with GA (aOR: 1.69; 95% CI: 1.11 to 2.56). Posterior circulation stroke was overrepresented in the GA group (29.6%) and may be a reason for the worse outcomes in the GA group. CONCLUSIONS: Patients who received LA or CS had better neurological outcomes than those who received GA within extended time windows in a real-world setting.

Time to Treatment With Intravenous Thrombolysis Before Thrombectomy and Functional Outcomes in Acute Ischemic Stroke: A Meta-Analysis.

Importance: The benefit of intravenous thrombolysis (IVT) for acute ischemic stroke declines with longer time from symptom onset, but it is not known whether a similar time dependency exists for IVT followed by thrombectomy. Objective: To determine whether the benefit associated with IVT plus thrombectomy vs thrombectomy alone decreases with treatment time from symptom onset. Design, Setting, and Participants: Individual participant data meta-analysis from 6 randomized clinical trials comparing IVT plus thrombectomy vs thrombectomy alone. Enrollment was between January 2017 and July 2021 at 190 sites in 15 countries. All participants were eligible for IVT and thrombectomy and presented directly at thrombectomy-capable stroke centers (n = 2334). For this meta-analysis, only patients with an anterior circulation large-vessel occlusion were included (n = 2313). Exposure: Interval from stroke symptom onset to expected administration of IVT and treatment with IVT plus thrombectomy vs thrombectomy alone. Main Outcomes and Measures: The primary outcome analysis tested whether the association between the allocated treatment (IVT plus thrombectomy vs thrombectomy alone) and disability at 90 days (7-level modified Rankin Scale [mRS] score range, 0 [no symptoms] to 6 [death]; minimal clinically important difference for the rates of mRS scores of 0-2: 1.3%) varied with times from symptom onset to expected administration of IVT. Results: In 2313 participants (1160 in IVT plus thrombectomy group vs 1153 in thrombectomy alone group; median age, 71 [IQR, 62 to 78] years; 44.3% were female), the median time from symptom onset to expected administration of IVT was 2 hours 28 minutes (IQR, 1 hour 46 minutes to 3 hours 17 minutes). There was a statistically significant interaction between the time from symptom onset to expected administration of IVT and the association of allocated treatment with functional outcomes (ratio of adjusted common odds ratio [OR] per 1-hour delay, 0.84 [95% CI, 0.72 to 0.97], P = .02 for interaction). The benefit of IVT plus thrombectomy decreased with longer times from symptom onset to expected administration of IVT (adjusted common OR for a 1-step mRS score shift toward improvement, 1.49 [95% CI, 1.13 to 1.96] at 1 hour, 1.25 [95% CI, 1.04 to 1.49] at 2 hours, and 1.04 [95% CI, 0.88 to 1.23] at 3 hours). For a mRS score of 0, 1, or 2, the predicted absolute risk difference was 9% (95% CI, 3% to 16%) at 1 hour, 5% (95% CI, 1% to 9%) at 2 hours, and 1% (95% CI, -3% to 5%) at 3 hours. After 2 hours 20 minutes, the benefit associated with IVT plus thrombectomy was not statistically significant and the point estimate crossed the null association at 3 hours 14 minutes. Conclusions and Relevance: In patients presenting at thrombectomy-capable stroke centers, the benefit associated with IVT plus thrombectomy vs thrombectomy alone was time dependent and statistically significant only if the time from symptom onset to expected administration of IVT was short.