Symptomatic Intracranial Hemorrhage Research Articles

Endovascular Versus Medical Management in Distal Medium Vessel Occlusion Stroke: The DUSK Study.

Endovascular treatment (EVT) is part of the usual care for proximal vessel occlusion strokes. However, the safety and effectiveness of EVT for distal medium vessel occlusions remain unclear. We sought to compare the clinical outcomes of EVT to medical management (MM) for isolated distal medium vessel occlusions. This is a retrospective analysis of prospectively collected data from seven comprehensive stroke centers. Patients were included if they had isolated distal medium vessel occlusion strokes due to middle cerebral artery M3/M4, anterior cerebral artery A2/A3, or posterior cerebral artery P1/P2 segments. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included 90-day good (mRS score, 0-2) and excellent (mRS score, 0-1) outcomes. Safety measures included symptomatic intracranial hemorrhage and 90-day mortality. A total of 321 patients were included in the analysis (EVT, 179; MM, 142; 40.8% treated with intravenous thrombolysis). In the inverse probability of treatment weighting model, there were no significant differences between EVT and MM in terms of the overall degree of disability (mRS ordinal shift; adjusted odds ratio [aOR], 1.25 [95% CI, 0.95-1.64]; P=0.110), rates of good (mRS score, 0-2; aOR, 1.32 [95% CI, 0.97-1.80]; P=0.075) and excellent (aOR, 1.32 [95% CI, 0.94-1.85]; P=0.098) outcomes, or mortality (aOR, 1.20 [95% CI, 0.78-1.85]; P=0.395) at 90 days. The multivariable regression model showed similar findings. Moreover, there was no difference between EVT and MM in rates of symptomatic intracranial hemorrhage in the multivariable regression model (aOR, 0.57 [95% CI, 0.21-1.58]; P=0.277), but the inverse probability of treatment weighting model showed a lower likelihood of symptomatic intracranial hemorrhage (aOR, 0.46 [95% CI, 0.24-0.85]; P=0.013) in the EVT group. This multicenter study failed to demonstrate any significant outcome differences among patients with isolated distal medium vessel occlusions treated with EVT versus MM. These findings reinforce clinical equipoise. Randomized clinical trials are ongoing and will provide more definite evidence.

Early vs Late Anticoagulation in Minor, Moderate, and Major Ischemic Stroke With Atrial Fibrillation: Post Hoc Analysis of the ELAN Randomized Clinical Trial.

Whether infarct size modifies the treatment effect of early vs late direct oral anticoagulant (DOAC) initiation in people with ischemic stroke and atrial fibrillation is unknown. To assess whether infarct size modifies the safety and efficacy of early vs late DOAC initiation. Post hoc analysis of participants from the multinational (>100 sites in 15 countries) randomized clinical Early Versus Later Anticoagulation for Stroke With Atrial Fibrillation (ELAN) trial who had (1) acute ischemic stroke, (2) atrial fibrillation, and (3) brain imaging available before randomization. The ELAN trial was conducted between October 2017 and December 2022. Data were analyzed from October to December 2023 for this post hoc analysis. Early vs late DOAC initiation after ischemic stroke. Early DOAC initiation was within 48 hours for minor or moderate stroke or on days 6 to 7 for major stroke; late DOAC initiation was on days 3 to 4 for minor stroke, days 6 to 7 for moderate stroke, and days 12 to 14 for major stroke. The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, extracranial bleeding, systemic embolism, or vascular death within 30 days. The outcome was assessed according to infarct size (minor, moderate, or major) using odds ratios and risk differences between treatment arms. Interrater reliability for infarct size between the core laboratory and local raters was assessed, and whether this modified the estimated treatment effects was also examined. A total of 1962 of the original 2013 participants (909 [46.3%] female; median [IQR] age, 77 [70-84] years) were included. The primary outcome occurred in 10 of 371 participants (2.7%) with early DOAC initiation vs 11 of 364 (3.0%) with late DOAC initiation among those with minor stroke (odds ratio [OR], 0.89; 95% CI, 0.38-2.10); in 11 of 388 (2.8%) with early DOAC initiation vs 14 of 392 (3.6%) with late DOAC initiation among those with moderate stroke (OR, 0.80; 95% CI, 0.35-1.74); and in 8 of 219 (3.7%) with early DOAC initiation vs 16 of 228 (7.0%) with late DOAC initiation among those with major stroke (OR, 0.52; 95% CI, 0.21-1.18). The 95% CI for the estimated risk difference of the primary outcome in early anticoagulation was -2.78% to 2.12% for minor stroke, -3.23% to 1.76% for moderate stroke, and -7.49% to 0.81% for major stroke. There was no significant treatment interaction for the primary outcome. For infarct size, interrater reliability was moderate (κ = 0.675; 95% CI, 0.647-0.702) for local vs core laboratory raters and strong (κ = 0.875; 95% CI, 0.855-0.894) between core laboratory raters. The treatment effect of early DOAC initiation did not differ in people with minor, moderate, or major stroke assessed by brain imaging. Early treatment was not associated with a higher rate of adverse events, especially symptomatic intracranial hemorrhage, for any infarct size, including major stroke. ClinicalTrials.gov Identifier: NCT03148457.

Expanding the Treatable Imaging Profile in Patients With Large Ischemic Stroke: Subanalysis From a Randomized Clinical Trial.

We aimed to examine the boundary of the ischemic core volume in patients undergoing endovascular thrombectomy (EVT) versus those receiving medical management to determine the minimum optimal size for favorable treatment outcomes. This is a prespecified substudy of the RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Large Ischemic Core Trial). Patients with large vessel occlusion were enrolled between November 2018 and September 2021 with a National Institutes of Health Stroke Scale score of at least 6 on admission and an Alberta Stroke Program Early Computed Tomography Score value of 3 to 5. We investigated the correlation between optimal quantified ischemic core volume, assessed solely using magnetic resonance diffusion-weighted imaging, and functional outcomes (modified Rankin Scale score, 0-3) at 90 days by predictive marginal plots. Final infarct volume and safety outcomes (symptomatic intracerebral hemorrhage and mortality) were also assessed. Of the 203 cases, 168 patients (85 in the EVT group versus 83 in the medical management group) were included. The median (interquartile range) core volume was 94 (65-160) mL in patients with EVT and 115 (71-141) mL in the medical management group (P=0.72). The predictive marginal probabilities of the 2 groups intersected at 128 mL for estimating functional outcomes. Symptomatic intracerebral hemorrhage and mortality within 90 days had overlay margins through all core volumes in both groups. The median final infarct volume (interquartile range) was smaller in the EVT group (142 [80-223] mL versus 211 [123-289] mL in the medical management group; P<0.001). In this prespecified analysis of a randomized clinical trial involving patients with large ischemic strokes, patients with an estimated core volume of up to 128 mL on diffusion-weighted imaging benefit from EVT. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03702413.

Boston Criteria v2.0 for Cerebral Amyloid Angiopathy Without Hemorrhage: An MRI-Neuropathologic Validation Study.

Updated criteria for the clinical-MRI diagnosis of cerebral amyloid angiopathy (CAA) have recently been proposed. However, their performance in individuals without symptomatic intracerebral hemorrhage (ICH) presentations is less defined. We aimed to assess the diagnostic performance of the Boston criteria version 2.0 for CAA diagnosis in a cohort of individuals ranging from cognitively normal to dementia in the community and memory clinic settings. Fifty-four participants from the Mayo Clinic Study of Aging or Alzheimer's Disease Research Center were included if they had an antemortem MRI with gradient-recall echo sequences and a brain autopsy with CAA evaluation. Performance of the Boston criteria v2.0 was compared with v1.5 using histopathologically verified CAA as the reference standard. The median age at MRI was 75 years (interquartile range 65-80) with 28/54 participants having histopathologically verified CAA (i.e., moderate-to-severe CAA in at least 1 lobar region). The sensitivity and specificity of the Boston criteria v2.0 were 28.6% (95% CI 13.2%-48.7%) and 65.3% (95% CI 44.3%-82.8%) for probable CAA diagnosis (area under the receiver operating characteristic curve [AUC] 0.47) and 75.0% (55.1-89.3) and 38.5% (20.2-59.4) for any CAA diagnosis (possible + probable; AUC 0.57), respectively. The v2.0 Boston criteria were not superior in performance compared with the prior v1.5 criteria for either CAA diagnostic category. The Boston criteria v2.0 have low accuracy in patients who are asymptomatic or only have cognitive symptoms. Additional biomarkers need to be explored to optimize CAA diagnosis in this population.

Association of functional outcomes between intravenous tirofiban and endovascular thrombectomy in imaging-screened patients with large vessel occlusion stroke: a secondary analysis of randomized clinical trial.

In the RESCUE BT (Endovascular Treatment With versus Without Tirofiban for Stroke Patients with Large Vessel Occlusion) trial, enrollment in extended time window was based on non-contrast computed tomography. To assess whether perioperative intravenous tirofiban would further enhance the clinical benefit of endovascular therapy in the RESCUE BT trial according to advanced imaging criteria based on current American Heart Association/American Stroke Association (AHA/ASA) guidelines. This is a secondary analysis of the RESCUE BT trial. Patients who were eligible for endovascular thrombectomy in the 6-hour window and met the criteria of the DAWN or DEFUSE 3 trials in the extended window according to the AHA/ASA guidelines were analyzed. The primary outcome was the distribution of the 90-day modified Rankin Scale (mRS) scores. Safety outcomes included the incidence of symptomatic intracranial hemorrhage (sICH) within 48 hours and 90-day mortality. A total of 652 patients (319 in tirofiban group and 333 in placebo group) who meeting the AHA/ASA guidelines were included in this analysis, with median (IQR) age of 68 (58-75) years, 278 (42.6%) were women. The median 90-day mRS score was 3 (IQR, 1-4) in the tirofiban group, and 3 (IQR, 1-4) in the placebo group. The adjusted common odds ratio (OR) for a lower level of disability with tirofiban than with placebo was 1.08 (95% confidence interval [CI], 0.83-1.42). The incidence of sICH (10.1% versus 6.3%; adjusted OR 1.70; [95% CI, 0.95-3.04]) was not significantly different between groups. However, intravenous tirofiban might be associated with lower disability level (adjusted common OR, 1.74 [95% CI, 1.14-2.65]; P=0.01) in patients with large artery atherosclerosis. There was no significant difference in the severity of disability at 90 days with intravenous tirofiban compared to placebo in patients who underwent endovascular therapy according to AHA/ASA guidelines. We observed potential benefits of tirofiban in patients with large artery atherosclerosis, but there was an increased risk of sICH in patients with cardioembolism stroke.

Comorbidity burden and outcomes after mechanical thrombectomy for large vessel occlusion: A retrospective analysis

ObjectivesPatients with acute ischemic stroke (AIS) often have an accumulation of pre-existing comorbidities, but its clinical impact on outcomes after mechanical thrombectomy (MT) remains unknown. Therefore, we examined whether comorbidity burden before AIS onset could predict clinical outcomes after MT. MethodsIn this retrospective cohort, we enrolled consecutive patients with community-onset AIS who underwent MT between April 2016 and December 2021. To evaluate each patient's comorbidity burden, we calculated Charlson comorbidity index (CCI), then classified the patients into the High CCI (≥ 3) and the Low CCI (< 3) groups. The primary outcome was a good neurological outcome at 90 days, defined as a modified Rankin scale 0-2 or no worse than the previous daily conditions. All-cause mortality at 90 days and hemorrhagic complications after MT were also compared between the two groups. We estimated the odds ratios and their confidence intervals using a multivariable logistic regression model. ResultsA total of 388 patients were enrolled, of whom 86 (22.2%) were classified into the High CCI group. Patients in the High CCI group were less likely to achieve a good neurological outcome (adjusted odds ratio of 0.26 [95% confidence interval, 0.12–0.58]). Moreover, symptomatic intracranial hemorrhage was more common in the High CCI (14.0% vs. 4.6%; adjusted odds ratio, 4.10 [95% confidence interval, 1.62–10.3]). ConclusionsComorbidity burden assessed by CCI was associated with clinical outcomes after MT. CCI has the potential to become a simple and valuable tool for predicting neurological prognosis among patients with AIS and MT.

Efficacy and safety of intravenous tenecteplase compared to alteplase before mechanical thrombectomy in acute ischemic stroke: a meta-analysis.

The benefits and risks of tenecteplase (TNK) versus alteplase (ALT) have recently been assessed in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy (MT) with diverse results. Due to its high fibrin specificity and lack of excitotoxicity, TNK may have a higher efficacy and safety profile. This study aimed to evaluate the benefits and risks of TNK compared to ALT in AIS patients prior to thrombectomy. We systematically searched four key databases, PubMed, Embase, Web of Science and Cochrane Library until January 27, 2024 for clinical studies evaluating the effects of TNK versus ALT in patients with large vessel occlusion undergoing MT. A random-effect meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Ten studies involving 3722 patients receiving TNK (1266 patients) or ALT (2456 patients) were included (age: 69.05 ± 14.95years; 55.64% male). Compared to ALT-treated patients, TNK-treated patients demonstrated significantly higher rates of early recanalization (odds ratio 2.02, 95%-confidence interval 1.20-3.38, p = 0.008) without increased risk of symptomatic intracerebral hemorrhage (1.06, 0.64-1.76, p = 0.82) or intracerebral hemorrhage (1.21, 0.66-2.25, p = 0.54). TNK-treated patients showed similar rates of functional independence at 90days (1.13, 0.87-1.46, p = 0.37) as ALT-treated patients, but lower rates of mortality within 90days (0.65, 0.44-0.96, p = 0.03). TNK is superior to ALT in achieving early recanalization and is associated with lower mortality within 90days in AIS patients undergoing MT. Compared with ALT, TNK does not significantly alter functional independence at 90days, symptomatic intracerebral hemorrhage or intracerebral hemorrhage.

Anesthesia modality in endovascular treatment for distal medium vessel occlusion stroke: intention-to-treat propensity score-matched analysis

BackgroundThe optimal anesthesia modality during endovascular treatment (EVT) for distal medium vessel occlusion (DMVO) stroke is uncertain. We aimed to evaluate the association of the anesthesia modality with procedural and...

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

Background and purposeThe 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...

Comparative Analysis of Tenecteplase versus Alteplase in Acute Ischemic Stroke: A Multicentric Observational Study from Eastern India

Abstract Background: Tenecteplase is used as an alternative to alteplase and is considered noninferior for thrombolysis in acute ischemic stroke. Objectives: To compare the effectiveness and adverse effects of tenecteplase and alteplase in the real-world management of acute ischemic stroke. Materials and Methods: In this retrospective observational study, we collected data from acute ischemic stroke patients admitted in six hospitals in West Bengal, India, and were thrombolysed with tenecteplase or alteplase between July 2021 and June 2022. Demographic data, baseline parameters, hospital course, and 3-month follow-up data were collected. The percentage of patients achieving a score of 0–2 in the modified Ranking scale at 3 months, rate of symptomatic intracranial hemorrhage, and all-cause mortality within 3 months were the main parameters of comparison between the two thrombolytic agents. Results: A total of 162 patients were initially included in this study. Eight patients were excluded due to unavailability of follow-up data. Among the remaining patients, 71 patients received tenecteplase and 83 patients received alteplase. There was no statistically significant difference between tenecteplase and alteplase with respect to the percentage of patients achieving functional independence (modified Rankin scale score 0–2) at 3 months (53.5% vs. 60.2%, P = 0.706), rate of symptomatic intracranial hemorrhage (5.6% vs. 10.8%, P = 0.246), and all-cause mortality at 3 months (11.3% vs. 15.7%, P = 0.628). Conclusion: The effectiveness of tenecteplase is comparable to alteplase in the real-world management of acute ischemic stroke. Symptomatic intracranial hemorrhage and all-cause mortality rates are also similar in real-world practice.

Contemporary Prestroke Dual Antiplatelet Use and Symptomatic Intracerebral Hemorrhage Risk After Thrombolysis

Intravenous alteplase (IV-tPA) can be administered to patients with acute ischemic stroke but is associated with symptomatic intracerebral hemorrhage (sICH). It is unclear if patients taking prestroke dual antiplatelet therapy (DAPT) are at higher risk of sICH. To determine the associated risk of sICH in patients taking prestroke dual antiplatelet therapy receiving alteplase for acute ischemic stroke using propensity score matching analysis. This cohort study used data from the American Heart Association and American Stroke Association Get With The Guidelines-Stroke (GWTG-Stroke) registry between 2013 and 2021. Data were obtained from hospitals in the GWTG-Stroke registry. This study included patients hospitalized with acute ischemic stroke and treated with IV-tPA. Data were analyzed from January 2013 to December 2021. Prestroke DAPT before treatment with IV-tPA for acute ischemic stroke. sICH, In-hospital death, discharge modified Rankin scale score, and other life-threatening systemic hemorrhages. Of 409 673 participants, 321 819 patients (mean [SD] age, 68.6 [15.1] years; 164 587 female [51.1%]) who were hospitalized with acute ischemic stroke and treated with IV-tPA were included in the analysis. The rate of sICH was 2.9% (5200 of 182 344), 3.8% (4457 of 117 670), and 4.1% (893 of 21 805) among patients treated with no antiplatelet therapy, single antiplatelet therapy (SAPT), and DAPT, respectively (P < .001). In adjusted analyses after propensity score subclassification, both SAPT (odds ratio [OR], 1.13; 95% CI, 1.07-1.19) and DAPT (OR, 1.28; 95% CI, 1.14-1.42) were associated with increased risks of sICH. Prestroke antiplatelet medications were associated with lower odds of discharge mRS score of 2 or less compared with no medication (SAPT OR, 0.92; 95% CI, 0.90-0.95; DAPT OR, 0.94; 95% CI, 0.88-0.98). Results of a subgroup analysis of patients taking DAPT exposed to aspirin-clopidogrel vs aspirin-ticagrelor combination therapy were not significant (OR, 1.35; 95% CI, 0.84-1.86). Prestroke DAPT was associated with a significantly elevated risk of sICH among patients with ischemic stroke who were treated with thrombolysis; however, the absolute increase in risk was small. Patients exposed to antiplatelet medications did not have excess sICH compared with landmark trials, which demonstrated overall clinical benefit of thrombolysis therapy for acute ischemic stroke.

Hypoperfusion index ratio and pretreatment with intravenous thrombolysis are independent predictors of good functional outcome in acute ischemic stroke patients with large vessel occlusion treated with acute reperfusion therapies.

We aimed to investigate the performance of several neuroimaging markers provided by perfusion imaging of Acute Ischemic Stroke (AIS) patients with large vessel occlusion (LVO) in order to predict clinical outcomes following reperfusion treatments. We prospectively evaluated consecutive AIS patients with LVO who were treated with reperfusion therapies, during a six-year period. In order to compare patients with good (mRS scores 0-2) and poor (mRS scores 3-6) functional outcomes, data regarding clinical characteristics, the Alberta Stroke Programme Early Computed Tomography Score (ASPECTS) based on unenhanced computed tomography (CT), CT angiography collateral status and perfusion parameters including ischemic core, hypoperfusion volume, mismatch volume between core and penumbra, Tmax > 10s volume, CBV index and the Hypoperfusion Index Ratio (HIR) were assessed. A total of 84 acute stroke patients with LVO who met all the inclusion criteria were enrolled. In multivariable logistic regression models increasing age (odds ratio [OR]: 0.93; 95%CI: 0.88-0.96, p = 0.001), lower admission National Institute of Health Stroke Scale (NIHSS)-score (OR: 0.88; 95%CI: 0.80-0.95, p = 0.004), pretreatment with intravenous thrombolysis (OR: 3.83; 95%CI: 1.29-12.49, p = 0.019) and HIR (OR:0.36; 95%CI: 0.10-0.95, p = 0.042) were independent predictors of good functional outcome at 3months. The initial univariable associations between HIR and higher likelihood for symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2 (PH2) were attenuated in multivariable analyses failing to reach statistical significance. Our pilot observational study of unselected AIS patients with LVO treated with reperfusion therapies demonstrated that pre-treatment low HIR in perfusion imaging and IVT were associated with better functional outcomes.

Low caveolin-1 levels and symptomatic intracranial haemorrhage risk in large-vessel occlusive stroke patients after endovascular thrombectomy.

Caveolin-1 (Cav-1) is reported to mediate blood-brain barrier integrity after ischaemic stroke. Our purpose was to assess the role of circulating Cav-1 levels in predicting symptomatic intracranial haemorrhage (sICH) amongst ischaemic stroke patients after endovascular thrombectomy (EVT). Patients with large-vessel occlusive stroke after EVT from two stroke centres were prospectively included. Serum Cav-1 level was tested after admission. sICH was diagnosed according to the Heidelberg Bleeding Classification. Of 325 patients (mean age 68.6 years; 207 men) included, 47 (14.5%) were diagnosed with sICH. Compared with patients without sICH, those with sICH had a lower concentration of Cav-1. After adjusting for potential confounders, multivariate regression analysis demonstrated that the increased Cav-1 level was associated with a lower sICH risk (odds ratio 0.055; 95% confidence interval 0.005-0.669; p = 0.038). Similar results were obtained when Cav-1 levels were analysed as a categorical variable. Using a logistic regression model with restricted cubic splines, a linear and negative association of Cav-1 concentration was found with sICH risk (p = 0.001 for linearity). Furthermore, the performance of the conventional risk factors model in predicting sICH was substantially improved after addition of the Cav-1 levels (integrated discrimination index 2.7%, p = 0.002; net reclassification improvement 39.7%, p = 0.007). Our data demonstrate that decreased Cav-1 levels are related to sICH after EVT. Incorporation of Cav-1 into clinical decision-making may help to identify patients at a high risk of sICH and warrants further consideration.

Incidence and predictors of intracranial hemorrhage after intravenous thrombolysis with tenecteplase.

Despite its increasing use, there are limited data on the risk of intracranial hemorrhage (ICH) after intravenous thrombolysis with tenecteplase in the setting of acute ischemic stroke. Our aim was to investigate the incidence and predictors of ICH after tenecteplase administration. We reviewed data from the prospective ongoing multicenter TETRIS (Tenecteplase Treatment in Ischemic Stroke) registry. Patients with available day-1 imaging were included in this study. Clinical, imaging and biological variables were collected. Follow-up imaging performed 24 h after IVT was locally reviewed by senior neuroradiologists and neurologists. The incidence of parenchymal hematoma (PH) and any ICH were investigated. Potential predictors of PH and any ICH were assessed in multivariable logistic regressions. Subgroup analyses focusing on patients intended for endovascular treatment were performed. PH and any ICH occurred in 126/1321 (incidence rate: 9.5%, 95% CI 8.1-11.2) and 521/1321 (39.4%, 95% CI 36.8-42.1) patients, respectively. Symptomatic ICH was observed in 77/1321 (5.8%; 95% CI 4.7-7.2). PH occurrence was significantly associated with poorer functional outcomes (p < 0.0001) and death (p < 0.0001) after 3 months. Older age (aOR = 1.03; 95% CI 1.01-1.05), male gender (aOR = 2.07; 95% CI 1.28-3.36), a history of hypertension (aOR = 2.08; 95% CI 1.19-3.62), a higher baseline NIHSS (aOR = 1.07; 95% CI 1.03-1.10) and higher admission blood glucose level (aOR = 1.12; 95% CI 1.05-1.19) were independently associated with PH occurrence. Similar associations were observed in the subgroup of patients intended for endovascular treatment. We quantified the incidence of ICH after IVT with tenecteplase in a real-life prospective registry and determined independent predictors of ICH. These findings allow to identify patients at high risk of ICH.

Safety and clinical outcomes of endovascular therapy versus medical management in late presentation of large ischemic stroke.

The benefit of endovascular therapy (EVT) among stroke patients with large ischemic core (ASPECTS 0-5) in the extended time window outside of trial settings remains unclear. We analyzed the effect of EVT among these stroke patients in real-world settings. The CT for Late Endovascular Reperfusion (CLEAR) study recruited patients from 66 centers in 10 countries between 01/2014 and 05/2022. The extended time-window was defined as 6-24 h from last-seen-well to treatment. The primary outcome was shift of the 3-month modified Rankin scale (mRS) score. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality. Outcomes were analyzed with ordinal and logistic regressions. Among 5098 screened patients, 2451 were included in the analysis (median age 73, 55% women). Of patients with ASPECTS 0-5 (n = 310), receiving EVT (n = 209/310) was associated with lower 3-month mRS when compared to medical management (median 4 IQR 3-6 vs 6 IQR 4-6; aOR 0.4, 95% CI 0.2-0.7). Patients undergoing EVT had higher sICH (11.2% vs 4.0%; aOR 4.1, 95% CI 1.2-18.8) and lower mortality (31.6% vs 58.4%, aOR 0.4; 95% CI 0.2-0.9) compared to medically managed patients. The relative benefit of EVT was comparable between patients with ASPECTS 0 and 5 and 6-10 in the extended time window (interaction aOR 0.9; 95% CI 0.5-1.7). In the extended time window, patients with ASPECTS 0-5 may have preserved relative treatment benefit of EVT compared to patients with ASPECTS 6-10. These findings are in line with recent trials showing benefit of EVT among real-world patients with large ischemic core in the extended time window. clinicaltrials.gov; Unique identifier: NCT04096248.

The pEGASUS-HPC stent system for intracranial arterial stenosis: a single-center case series.

Intracranial arterial stenting is a technique for the treatment of symptomatic stenosis. In this single-center retrospective case series we evaluated a novel low profile laser-cut stent with an antithrombogenic hydrophilic polymer coating (pEGASUS-HPC, Phenox GmbH, Bochum, Germany) for the treatment of intracranial stenosis in the setting of acute ischemic stroke and elective cases. All patients treated with pEGASUS-HPC for one or more intracranial arterial stenoses at our institution were retrospectively included. Clinical, imaging and procedural parameters as well as clinical and imaging follow-up data were collected. We performed 43 interventions in 41 patients with 42 stenoses in our neurovascular center between August 2021 and February 2024. Twenty-one patients (51.2%) were female and the mean±SD age was 71±10.8 years. Thirty-seven (86.1%) procedures were performed in the setting of endovascular acute ischemic stroke treatment. Technical or procedural complications occurred in seven patients (16.3%), six in the thrombectomy group and one in the elective group. One stent-related hemorrhagic complication (subarachnoid hemorrhage) occurred in emergency cases and symptomatic intracerebral hemorrhage occurred in one patient treated in an elective setting. Overall stenosis reduction following pEGASUS-HPC stent implantation was 53.0±18.0%. On follow-up imaging, which was available for 16 patients (37.2%) after an average of 32±58.6 days, 62.5% of the stents were patent. Our single-center case series demonstrates the feasibility of using the pEGASUS-HPC stent system, especially in emergency situations when thrombectomy fails.

Rescue Therapy for Failed Mechanical Thrombectomy in Acute Ischemic Stroke: A Pooled Analysis of the Society of Vascular and Interventional Neurology Registry.

We aimed to evaluate the association between rescue therapy (RT) and functional outcomes compared to medical management (MM) in patients presenting after failed mechanical thrombectomy (MT). This cross-sectional study utilized prospectively collected and maintained data from the Society of Vascular and Interventional Neurology Registry, spanning from 2011 to 2021. The cohort comprised patients with large vessel occlusions (LVOs) with failed MT. The primary outcome was the shift in the degree of disability, as gauged by the modified Rankin Scale (mRS) at 90 days. Additional outcomes included functional independence (90-day mRS score of 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. Of a total of 7,018 patients, 958 presented failed MT and were included in the analysis. The RT group comprised 407 (42.4%) patients, and the MM group consisted of 551 (57.5%) patients. After adjusting for confounders, the RT group showed a favorable shift in the overall 90-day mRS distribution (adjusted common odds ratio = 1.79, 95% confidence interval [CI] = 1.32-2.45, p < 0.001) and higher rates of functional independence (RT: 28.8% vs MM: 15.7%, adjusted odds ratio [aOR] = 1.93, 95% CI = 1.21-3.07, p = 0.005) compared to the MM group. RT also showed lower rates of sICH (RT: 3.8% vs MM: 9.1%, aOR = 0.52, 95% CI = 0.28-0.97, p = 0.039) and 90-day mortality (RT: 33.4% vs MM: 45.5%, aOR = 0.61, 95% CI = 0.42-0.89, p = 0.009). Our findings advocate for the utilization of RT as a potential treatment strategy for cases of LVO resistant to first-line MT techniques. Prospective studies are warranted to validate these observations and optimize the endovascular approach for failed MT patients. ANN NEUROL 2024.

Early Versus Late Initiation of Direct Oral Anticoagulants After Ischemic Stroke in People With Atrial Fibrillation and Hemorrhagic Transformation: Prespecified Subanalysis of the Randomized-controlled ELAN Trial.

Whether hemorrhagic transformation (HT) modifies the treatment effect of early versus late initiation of direct oral anticoagulation (DOAC) in people with ischemic stroke and atrial fibrillation is unknown. This is a post-hoc analysis of the ELAN trial. The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage (sICH), major extracranial bleeding, systemic embolism, or vascular death within 30 days. Secondary outcomes were the individual components, 30- and 90-day functional outcome. We estimated outcomes based on HT, subclassified as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) on pre-randomization imaging (core-lab rating) using adjusted risk differences (aRD) between treatment arms. Overall, 247/1970 (12.5%) participants had HT (114 HI 1, 77 HI 2, 34 PH 1, 22 PH 2). For the primary outcome, the estimated aRD (early versus late) was -2.2% (-7.8 to 3.5%) in people with HT (HI: -4.7%, -10.8 to 1.4%; PH: 6.1%, -8.4 to 20.7%), and -0.9% (-2.6 to 0.8%) in people without. Numbers of sICH were identical in people with and without HT. With early treatment, the estimated aRD for poor 90-day functional outcome (mRS 3-6) was 11.4% (-0.9 to 23.7%) in participants with HT (HI: 7.2%, -6.6 to 21.0%; PH: 25.1%, 0.2 to 50.0%), and -2.6% (-7.1 to 1.8%) in people without HT. We found no evidence of major treatment effect heterogeneity or safety concerns with early versus late DOAC initiation in people with and without HT. However, early DOAC initiation may worsen functional outcomes in people with PH.

PCSK9 inhibitor in acute ischemic stroke patient receiving mechanical thrombectomy: early outcomes and safety

BackgroundLipid-lowering therapies are mainstays in reducing recurrence after acute ischemic stroke (AIS). Evolocumab, a Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, is a promising lipid-lowering agent known to decrease LDL cholesterol and mitigate vascular events alongside statins. However, its effects on the early functional outcomes post-mechanical thrombectomy (MT) remain unclear. This study aimed to assess the short-term effects and incidence of bleeding events after the early, off-label use of PCSK9 inhibitors in AIS patients undergoing MT.MethodsWe retrospectively analyzed patients who had MT at a Regional Stroke Center from December 2018 to April 2023. Our primary outcome was discharge functional outcomes. Secondary outcomes included early neurologic deterioration (END), symptomatic intracerebral hemorrhage (sICH), 3-month functional outcomes, 3-month recurrence rate, and lipid profiles.ResultsOf 261 patients (mean age 69.2 ± 11.7, men 42.9%), 42 were administered evolocumab peri-procedurally. While baseline characteristics were similar between the two groups, evolocumab group demonstrated improved discharge outcomes, with a lower mean NIHSS (8.8 ± 6.8 vs. 12.4 ± 9.8, p = 0.02) and a higher percentage of patients with discharge mRS ≤ 3 (52.4% vs. 35.6%, p = 0.041). The 3-month follow-up show a non-significant trend toward an improved outcome in the evolocumab group. Multivariable analysis indicated that evolocumab had a potential impact on favorable discharge outcomes (aOR 1.98[0.94–4.22] for mRS ≤ 3 and 0.47[0.27–0.84] for lower ordinal mRS). Notably, evolocuamb users exhibited fewer instances of END and sICH, although they do not reach statistical significance. Additionally, the evolocumab group demonstrated potential benefits in LDL cholesterol reduction over time.ConclusionEarly use of evolocumab in AIS patients undergoing MT appeared to be safe and associated with better early functional outcomes. The potential benefit of the PCSK9 inhibitor shown here warrants further prospective studies.

Associations of diabetes status and glucose measures with outcomes after endovascular therapy in patients with acute ischemic stroke: an analysis of the nationwide TREAT-AIS registry

BackgroundHyperglycemia affects the outcomes of endovascular therapy (EVT) for acute ischemic stroke (AIS). This study compares the predictive ability of diabetes status and glucose measures on EVT outcomes using nationwide registry data.MethodsThe study included 1,097 AIS patients who underwent EVT from the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke. The variables analyzed included diabetes status, admission glucose, glycated hemoglobin (HbA1c), admission glucose-to-HbA1c ratio (GAR), and outcomes such as 90-day poor functional outcome (modified Rankin Scale score ≥ 2) and symptomatic intracranial hemorrhage (SICH). Multivariable analyses investigated the independent effects of diabetes status and glucose measures on outcomes. A receiver operating characteristic (ROC) analysis was performed to compare their predictive abilities.ResultsThe multivariable analysis showed that individuals with known diabetes had a higher likelihood of poor functional outcomes (odds ratios [ORs] 2.10 to 2.58) and SICH (ORs 3.28 to 4.30) compared to those without diabetes. Higher quartiles of admission glucose and GAR were associated with poor functional outcomes and SICH. Higher quartiles of HbA1c were significantly associated with poor functional outcomes. However, patients in the second HbA1c quartile (5.6–5.8%) showed a non-significant tendency toward good functional outcomes compared to those in the lowest quartile (&amp;lt;5.6%). The ROC analysis indicated that diabetes status and admission glucose had higher predictive abilities for poor functional outcomes, while admission glucose and GAR were better predictors for SICH.ConclusionIn AIS patients undergoing EVT, diabetes status, admission glucose, and GAR were associated with 90-day poor functional outcomes and SICH. Admission glucose was likely the most suitable glucose measure for predicting outcomes after EVT.