Abstract Number ‐ 98: Intravenous dose‐adjusted cangrelor use for neuroendovascular procedures: An institutional experience

Introduction The optimal antiplatelet therapy regimen for certain neuroendovascular procedures remains unclear. This study investigates the safety and feasibility of intravenous dose‐adjusted cangrelor in patients undergoing neuroendovascular procedures. Methods We conducted a retrospective chart review of all consecutive patients who underwent neuroendovascular procedures and were placed on intravenous cangrelor between September 1, 2020 and March 13, 2022. Cangrelor was administered as a 15 mcg/kg bolus followed by 2 mcg/kg/min infusion titrated to goal P2Y12reaction unit (PRU) level of 50 to 150, and then transitioned to oral antiplatelet therapy. Demographic characteristics, interventional variables, and clinical outcomes were collected. Results A total of 50 patients were included. The mean age (years) was 56.0±18.6, and 26 (52.0%) were males. Most patients were African American (n = 39/48, 81.3%). The most common comorbidities were hypertension (n = 25/49, 51.0%), active smoking status (n = 14/40, 35.0%), and prior ischemic stroke (n = 13/49, 26.5%). Intravenous thrombolysis was used in 4 patients (8.0%). Cangrelor infusion was used for the following procedures: embolization (n = 10/50, 20.0%), embolization and stent placement (n = 9/50, 18.0%), thrombectomy alone (n = 5/50, 10.0%), thrombectomy and stent placement (n = 10/50, 20.0%), and stent placement only (n = 14/50, 28.0%). Stent placement occurred intracranially beyond petrous segment of the internal carotid artery in 18 patients, remainder of internal or common carotid artery in 12 patients, and both intracranial and carotid arteries in 3 patients. PRU levels were measured in 48 patients (96.0%), with 26 patients (54.2%) achieving a PRU level of 50–150 greater than or equal to 50% of the time. Approximately 51.5% of the patients had a favorable functional outcome with modified Rankin Scale (mRS) score of 0 to 2 at 90 days (n = 17/33).During 1‐year follow up, approximately 4 patients had recurrent or new strokes (9.5%), 1 patient had in‐stent thrombosis (2.9%) and 1 patient with symptomatic intracranial hemorrhage [sICH] (2.4%), both while not on antiplatelet therapy, 2 patients with asymptomatic intracranial hemorrhage [ICH] (4.8%), and no gastrointestinal bleeding events were recorded. When stratified by PRU level, there were no significant differences in sICH (p = 0.841) or asymptomatic ICH (p = 0.853). Conclusions To our knowledge, this is the first report to demonstrate the safety and effectiveness of intravenous cangrelor use titrated based on platelet function testing in the largest cohort of patients who underwent neuroendovascular procedures to date. Further studies, including comparative studies to standard dose maintenance cangrelor, are necessary

Abstract Number ‐ 163: Underlying ICAD is associated with worse outcomes in acute large vessel occlusion undergoing endovascular thrombectomy

Introduction Acute large vessel occlusion (LVO) can be secondary to thromboembolism or intracranial atherosclerotic disease (ICAD). Data on LVO management due to underlying ICAD are scarce. We hypothesized that patients with ICAD have worse clinical outcomes following mechanical thrombectomy (MT) than those without ICAD. Methods We performed a retrospective analysis of consecutive patients who underwent MT for LVO in a large academic comprehensive stroke center between January 14, 2018 and October 24, 2021. Presence of ICAD at LVO site was determined by the interventionalist. We compared in‐hospital mortality, 90‐day mortality, and 90‐day modified Rankin Scale (mRS) scores between those with and without ICAD, in unadjusted and adjusting logistic regression models. Results Among 215 patients (mean age 67.1±16.0 years; 60.5% female; 80.5% Black, median NIHSS score 16), ICAD was present in 38 patients (17.7%). Diabetes and dyslipidemia were more common in those with ICAD (57.9% vs. 38.4%, p = 0.027 and 29.0% vs. 14.7%, p = 0.035, respectively). Substantial reperfusion (TICI ≥ 2b) was achieved less often (84.2% vs. 94.4%, p = 0.031) but symptomatic ICH was also less common in ICAD patients (0% vs. 9.0%, p = 0.054). In‐hospital and 90‐day mortality were more common (36.8% vs. 15.8%, p = 0.003 and 52.6% vs. 26.6%, p = 0.002, respectively) and favorable functional outcome (mRS 0–2) at 90 days was less common (7.9% vs. 33.9%, p = 0.001) in ICAD patients. After adjusting for prognostic variables, ICAD was independently associated with in‐hospital mortality (OR = 4.1, 95% CI 1.7‐9.7), 90‐day mortality (OR = 3.7, 95% CI 1.6‐8.6), and poor functional outcome at 90 days (OR = 5.5, 95% CI 1.6‐19.4). Conclusions Symptomatic ICAD in a predominantly African American cohort is associated with increased odds of mortality and poor functional outcome at 90 days in patients with LVO undergoing MT. Further research is warranted to understand factors associated with worse outcomes and investigate alternative interventional approaches and medical management in this high‐risk population

Endovascular thrombectomy with or without thrombolysis bridging in patients with acute ischaemic stroke: protocol for a systematic review, meta-analysis of randomised trials and cost-effectiveness analysis

Introduction Current published guidelines and meta-analyses comparing endovascular thrombectomy (EVT) alone versus EVT with bridging intravenous thrombolysis (IVT) suggest that EVT alone is non-inferior to EVT with bridging thrombolysis in achieving favourable functional outcome. Because of this controversy, we aimed to systematically update the evidence and meta-analyse data from randomised trials comparing EVT alone versus EVT with bridging thrombolysis, and performed an economic evaluation comparing both strategies.Methods and analysis We will conduct a systematic review of randomised controlled trials comparing EVT with or without bridging thrombolysis in patients presenting with large vessel occlusions. We will identify eligible studies by systematically searching the following databases from inception without any language restrictions: MEDLINE (through Ovid), Embase and the Cochrane Library. The following criteria will be used to assess eligibility for inclusion: (1) adult patients ≥18 years old; (2) randomised patients to EVT alone or to EVT with IVT; and (3) measured outcomes, including functional outcomes, at least 90 days after randomisation. Pairs of reviewers will independently screen the identified articles, extract information and assess the risk of bias of eligible studies. We will use the Cochrane Risk-of-Bias tool to evaluate risk of bias. We will also use the Grading of Recommendations, Assessment, Development and Evaluation approach to assess the certainty in evidence for each outcome. We will then perform an economic evaluation based on the extracted data.Ethics and dissemination This systematic review will not require a research ethics approval because no confidential patient data will be used. We will disseminate our findings by publishing the results in a peer-reviewed journal and via presentation at conferences.PROSPERO registration number CRD42022315608

Abstract Number ‐ 24: Endovascular thrombectomy with or without bridging thrombolysis in patients with ischemic stroke: A cost‐utility analysis

Introduction There is clinical equipoise behind bridging intravenous thrombolysis (BT) with endovascular thrombectomy (EVT). We performed a cost‐effectiveness analysis comparing EVT and BT versus EVT alone. Methods We conducted a model‐based cost‐utility analysis comparing the cost‐effectiveness of EVT alone vs. EVT and BT for patients with acute ischemic stroke. We used a decision tree to examine the short‐term costs and outcomes at 90 days after the index stroke. Subsequently, we developed a Markov state transition model to assess the costs and outcomes over 1‐year, 5‐year, and 20‐year time horizons. Treatment costs were based on administrative data. Clinical outcome inputs were derived from literature included in our systematic review. We considered the impact of disability and recurrent stroke on mortality risk, health‐related quality of life, and costs. We estimated total and incremental cost, quality‐adjusted life years (QALYs), and incremental cost‐effectiveness ratio (ICER), expressed as an incremental cost per QALY gained of EVT and BT compared with EVT alone.Probabilistic analysis was used to calculate the reference case estimates. Results The average costs per patient were estimated to be $55,503,$57,814, $68,183, and$84,946 for EVT only strategy, and $47,311,$49,556, $59,625, and$75,898 for EVT and BT over 90‐day, 1‐year, 5‐year, and 20‐year, respectively. The cost saving of EVT only strategy was driven by the avoided medication costs of IVT (ranging from $8,193 to$9,048). The additional thrombolytics led to slight decrease in QALY estimate during the 90‐day time horizon (loss of 0.0016 QALY), but a small gain over 1‐year, 5‐year, and 20‐year time horizons (0.0108, 0.0638, and 0.1481 QALY). With similar outcomes and less cost, the EVT only strategy was cost‐effective compared with EVT and BT. Analyses with longer time horizon show lower probabilities of EVT only strategy being cost‐effective. At a fixed willingness to pay threshold of $50,000, the probabilities of EVT only to be cost‐effective were 100$100,000 per QALY, the probabilities of EVT only strategy being cost‐effective was 22.8% over the 20‐year time horizon. Conclusions Our cost‐effectiveness model suggested that bridging with thrombolytics may not be cost‐effective for patients with acute ischemic stroke secondary to large vessel occlusion

Biomarkers of cavernous angioma with symptomatic hemorrhage

BACKGROUNDCerebral cavernous angiomas (CAs) with a symptomatic hemorrhage (CASH) have a high risk of recurrent hemorrhage and serious morbidity.METHODSEighteen plasma molecules with mechanistic roles in CA pathobiology were investigated in 114 patients and 12 healthy subjects. The diagnostic biomarker of a CASH in the prior year was derived as that minimizing the Akaike information criterion and validated using machine learning, and was compared with the prognostic CASH biomarker predicting bleeding in the subsequent year. Biomarkers were longitudinally followed in a subset of cases. The biomarkers were queried in the lesional neurovascular unit (NVU) transcriptome and in plasma miRNAs from CASH and non-CASH patients.RESULTSThe diagnostic CASH biomarker included a weighted combination of soluble CD14 (sCD14), VEGF, C-reactive protein (CRP), and IL-10 distinguishing CASH patients with 76% sensitivity and 80% specificity (P = 0.0003). The prognostic CASH biomarker (sCD14, VEGF, IL-1β, and sROBO-4) was confirmed to predict a bleed in the subsequent year with 83% sensitivity and 93% specificity (P = 0.001). Genes associated with diagnostic and prognostic CASH biomarkers were differentially expressed in CASH lesional NVUs. Thirteen plasma miRNAs were differentially expressed between CASH and non-CASH patients.CONCLUSIONShared and unique biomarkers of recent symptomatic hemorrhage and of future bleeding in CA are mechanistically linked to lesional transcriptome and miRNA. The biomarkers may be applied for risk stratification in clinical trials and developed as a tool in clinical practice.FUNDINGNIH, William and Judith Davis Fund in Neurovascular Surgery Research, Be Brave for Life Foundation, Safadi Translational Fellowship, Pritzker School of Medicine, and Sigrid Jusélius Foundation

Biomarkers of cavernous angioma with symptomatic hemorrhage

BACKGROUNDCerebral cavernous angiomas (CAs) with a symptomatic hemorrhage (CASH) have a high risk of recurrent hemorrhage and serious morbidity.METHODSEighteen plasma molecules with mechanistic roles in CA pathobiology were investigated in 114 patients and 12 healthy subjects. The diagnostic biomarker of a CASH in the prior year was derived as that minimizing the Akaike information criterion and validated using machine learning, and was compared with the prognostic CASH biomarker predicting bleeding in the subsequent year. Biomarkers were longitudinally followed in a subset of cases. The biomarkers were queried in the lesional neurovascular unit (NVU) transcriptome and in plasma miRNAs from CASH and non-CASH patients.RESULTSThe diagnostic CASH biomarker included a weighted combination of soluble CD14 (sCD14), VEGF, C-reactive protein (CRP), and IL-10 distinguishing CASH patients with 76% sensitivity and 80% specificity (P = 0.0003). The prognostic CASH biomarker (sCD14, VEGF, IL-1β, and sROBO-4) was confirmed to predict a bleed in the subsequent year with 83% sensitivity and 93% specificity (P = 0.001). Genes associated with diagnostic and prognostic CASH biomarkers were differentially expressed in CASH lesional NVUs. Thirteen plasma miRNAs were differentially expressed between CASH and non-CASH patients.CONCLUSIONShared and unique biomarkers of recent symptomatic hemorrhage and of future bleeding in CA are mechanistically linked to lesional transcriptome and miRNA. The biomarkers may be applied for risk stratification in clinical trials and developed as a tool in clinical practice.FUNDINGNIH, William and Judith Davis Fund in Neurovascular Surgery Research, Be Brave for Life Foundation, Safadi Translational Fellowship, Pritzker School of Medicine, and Sigrid Jusélius Foundation

Baseline Characteristics of Patients With Cavernous Angiomas With Symptomatic Hemorrhage in Multisite Trial Readiness Project

Background and purposeBrain cavernous angiomas with symptomatic hemorrhage (CASH) have a high risk of neurological disability from recurrent bleeding. Systematic assessment of baseline features and multisite validation of novel magnetic resonance imaging biomarkers are needed to optimize clinical trial design aimed at novel pharmacotherapies in CASH.MethodsThis prospective, multicenter, observational cohort study included adults with unresected, adjudicated brain CASH within the prior year. Six US sites screened and enrolled patients starting August 2018. Baseline demographics, clinical and imaging features, functional status (modified Rankin Scale and National Institutes of Health Stroke Scale), and patient quality of life outcomes (Patient-Reported Outcomes Measurement Information System-29 and EuroQol-5D) were summarized using descriptive statistics. Patient-Reported Outcomes Measurement Information System-29 scores were standardized against a reference population (mean 50, SD 10), and one-sample t test was performed for each domain. A subgroup underwent harmonized magnetic resonance imaging assessment of lesional iron content with quantitative susceptibility mapping and vascular permeability with dynamic contrast-enhanced quantitative perfusion.ResultsAs of May 2020, 849 patients were screened and 110 CASH cases enrolled (13% prevalence of trial eligible cases). The average age at consent was 46±16 years, 53% were female, 41% were familial, and 43% were brainstem lesions. At enrollment, ≥90% of the cohort had independent functional outcome (modified Rankin Scale score ≤2 and National Institutes of Health Stroke Scale score <5). However, perceived health problems affecting quality of life were reported in >30% of patients (EuroQol-5D). Patients had significantly worse Patient-Reported Outcomes Measurement Information System-29 scores for anxiety (P=0.007), but better depression (P=0.002) and social satisfaction scores (P=0.012) compared with the general reference population. Mean baseline quantitative susceptibility mapping and permeability of CASH lesion were 0.45±0.17 ppm and 0.39±0.31 mL/100 g per minute, respectively, which were similar to historical CASH cases and consistent across sites.ConclusionsThese baseline features will aid investigators in patient stratification and determining the most appropriate outcome measures for clinical trials of emerging pharmacotherapies in CASH