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Background and Purpose New studies have shown that endovascular thrombectomy (EVT) is safe and effective for acute ischemic stroke (AIS) patients with large ischemic areas. The aim of our study is to conduct a living systematic review and meta-analysis of randomized trials comparing EVT versus medical management only. Methods We searched MEDLINE, Embase, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing EVT versus medical management alone in AIS patients with large ischemic regions. We conducted our meta-analysis using fixed-effect models to compare functional independence, mortality, and symptomatic intracranial hemorrhage (sICH) between EVT and standard medical management only. We assessed the risk of bias using the Cochrane risk-of-bias tool and the certainty of evidence for each outcome using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Results Of 14,513 citations, we included 3 RCTs with a total of 1,010 participants. We found low-certainty evidence of possibly a large increase in the proportion of patients with functional independence (risk difference [RD] 30.3%, 95% CI 15.0% to 52.3%), low-certainty evidence of possibly a small non-significant decrease in mortality (RD -0.7%, 95% CI -3.8% to 3.5%), and low-certainty evidence of possibly a small non-significant increase in sICH (RD 3.1%, 95% CI -0.3% to 9.8%) for AIS patients with large infarcts who underwent EVT compared to medical management only. Conclusion Low-certainty evidence shows that there is possibly a large increase in functional independence, a small non-significant decrease in mortality, and a small non-significant increase in sICH amongst AIS patients with large infarcts undergoing EVT compared to medical management only.

Introduction Ticagrelor use has become more prominent in acute ischemic stroke management in the presence of clopidogrel resistance(1‐2). This study compares the effectiveness of aspirin plus ticagrelor at different doses versus clopidogrel in reducing the risk of recurrent stroke and other thrombotic events without increasing the risk of bleeding. Methods We performed a retrospective chart review of patients diagnosed with acute ischemic stroke at a large academic comprehensive stroke center from September 1, 2020, to July 1, 2022. A total of 3 separate groups, low‐dose ticagrelor (45 mg or 60 mg twice a day), full‐dose ticagrelor (90 mg twice a day) and clopidogrel (75 mg daily) were created. We compared baseline characteristics and completed a one‐way ANOVA to analyze for outcome measures such as in‐hospital mortality, 90‐day mortality, favorable functional outcome defined as modified Rankin Score (mRS) of 0‐2, at 90 days, symptomatic intracranial hemorrhage (sICH) and asymptomatic hemorrhage (aICH) between groups. All data was analyzed via IBM SPSS v28.0. Results A total of 445 patients were included in our study. The mean age was 66.1 ± 12.8 years and the majority of patients were female (52.9%). The most common ethnicity was African American (82.9%). Sixty patients were discharged on low‐dose ticagrelor, 39 on full dose ticagrelor and 351 on clopidogrel. A total of 162/433 (36.0%) had a presumed stroke etiology of intracranial atherosclerotic disease (ICAD). Only 24 patients received intravenous thrombolytics (5.3%) and 47 had stent placement (10.4%). Out of 445 patients, 288 were on aspirin 81 mg at time of discharge. Of that group, 228 were on both aspirin and clopidogrel, 60 were on aspirin and low‐dose ticagrelor and 39 were on aspirin and full‐dose ticagrelor. There was no statistical significance for new or recurrent ischemic stroke between groups (low‐dose vs full‐dose vs clopidogrel) determined by one‐way ANOVA (10.0% vs. 17.9% vs. 7.8%, F(2,103) = 0.01, p=0.99). Symptomatic ICH was also similar between the groups (3.3% vs. 2.6% vs. 1.1%, F(2,101) = 0.68, p=0.51). There was no significance for favorable functional outcomes and mortality as well (26.7% vs. 23.1% vs. 24.2%, F(2,173) = 0.62, p=0.54; 80.0% vs. 79.5% vs. 81.5%, F(2,150) = 1.5, p=0.22). Conclusion These findings suggest that a lower dose of ticagrelor may be a safe and effective alternative to full dose ticagrelor or clopidogrel for the prevention of recurrent ischemic stroke without increasing hemorrhagic complications. Larger randomized trials are necessary to further evaluate these findings.

Introduction Cocaine‐induced vasospasm of small vessels has long been proposed as a mechanism for ischemic stroke (1). However, there are limited studies to date that have classified cocaine‐related ischemic strokes under a subtype of the Trial of ORG 10127 in Acute Stroke Treatment (TOAST) criteria. This study aims to describe cocaine‐related ischemic strokes by TOAST criteria, treatment, and clinical outcome. Methods A retrospective review was performed to identify patients with acute ischemic stroke and a positive cocaine urine toxicology screen at our stroke center from June 2020 – May 2022. Baseline demographics, urine toxicology, National Institute of Health Stroke Scale (NIHSS) scores, neuroimaging, TOAST criteria, location of stroke, home medications, comorbidities, medical management, and in‐patient outcomes were collected. Data analysis was conducted on IBM SPSS Version 28. Results A total of 74 patients were identified to have a positive cocaine status on admission with a diagnosis of new strokes. The mean age was found to be age 60.8 years old with a majority male population at 73.0% (54/74). Seventy‐eight percent (58/74) were found to be cocaine positive on admission with the remaining endorsing a history of cocaine use. The most common category under the TOAST criteria was large artery atherosclerosis 39.2% (29/74). Among the cocaine‐positive cohort, 10.8% (8/74) of patients received thrombolytics. Most patients had intracranial atherosclerotic disease (46/74, 62.2%) on imaging and in the area of the stroke (41/74, 55.4%). Overall mortality was low (72/74, 97.3%) and modified Rankin score (mRS) at discharge was less than 3 for 59.5% (44/74) of patients. Conclusion Our data suggests that although cocaine may contribute to small vessel disease, cocaine‐related ischemic strokes may have a higher association with large artery atherosclerosis. This study highlights the importance of future larger studies to investigate atherosclerosis as a contributor to cocaine‐induced ischemic strokes.

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.

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%, 99.0%, and 65.9% over 90‐day, 1‐year, 5‐year, and 20‐year time horizons. At the willingness to pay thresholds of $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.

Introduction There has been an increase in use of ticagrelor in patients with ischemic stroke, particularly in the setting of clopidogrel resistance. Our study aims to retrospectively determine if aspirin plus ticagrelor at a reduced dose is effective in reducing the risk of recurrent stroke and/or other thrombotic events, without increasing the risk of bleeding. Methods In a prospectively maintained database, we performed a retrospective analysis of consecutive patients with acute ischemic stroke in a large academic comprehensive stroke center between September 1, 2020 to July 1, 2022. We compared in‐hospital mortality, 90‐day mortality, favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0 to 2, at 90 days, symptomatic intracranial hemorrhage (sICH), and asymptomatic intracranial hemorrhage (ICH), between patients on reduced‐dose ticagrelor versus those on full‐dose ticagrelor, in unadjusted and adjusted logistic regression models. Results We included 567 patients in our study. The mean age of these patients was 67.0 ± 15.0 years. Females represented 59.5% of the patients, and the majority of the patients were Black (80.0%). Intracranial atherosclerotic disease was the presumed stroke etiology in 96 patients (17.0%). Out of 567 patients, 432 were on a combination of both ticagrelor and aspirin. A total of 62 patients were on a reduced dose of ticagrelor (45 mg or 60 mg twice daily). The remaining 505 patients were on 90 mg twice daily dosing. New or recurrent ischemic stroke was similar across both groups (10.2% vs. 12.0%, p = 0.08). Symptomatic ICH was also found to be similar across both groups (8.2% vs. 9.3%, p = 0.06). Mortality or favorable functional outcome at 90 days also did not differ between the two groups (25.3% vs. 24.7%, p = 0.007; 28.2% vs. 27.3%, p = 0.006). Conclusions A lower dose of ticagrelor (45 or 60 mg twice daily) appears to be a safe and effective regimen in reducing risk of ischemic strokes without increasing hemorrhagic complications when compared to full‐dose ticagrelor at 90 mg twice daily. Further randomized trials are necessary to inform this recommendation.

Introduction Chronic subdural hematomas (SDH) have a higher prevalence among the elderly population and can cause significant morbidity and mortality when they recur after surgical intervention. Use of n‐butyl‐2‐cyanoacrylate (n‐BCA) has proven to be an effective and safe therapeutic agent for embolization of the middle meningeal artery (MMA). In our study, we present a retrospective analysis of 31 patients who underwent MMA embolization for chronic SDH. Methods In a prospectively maintained database in a single center, we retrospectively analyzed 31 patients admitted to our institution who were diagnosed with chronic SDH, acute on chronic SDH, and acute SDH, and underwent MMA embolization with n‐BCA between May 20th, 2021, and June 28th, 2022. Our primary endpoint was >50% SDH reduction on follow‐up imaging. Our secondary endpoint was all‐cause mortality. Patients were separated into outcome groups and their baseline demographic, clinical, and procedural variables were compared using t‐test, Wilcoxon rank‐sum test, chi‐squared test, and Fisher’s exact test. Through univariate logistic regression, we attempted to determine if these variables directly influenced SDH reduction and mortality. Results In our study, a total of 42 MMA embolizations for 31 patients were included. We found that a greater number of patients with hypertension (n = 23; p = 0.04), use of antiplatelet (AP) medication (n = 8; p = 0.02), and those who underwent MMA embolization via the radial approach (n = 18; p = 0.004) were among those with < 50% SDH reduction. We also found that MMA embolization via the femoral approach (n = 13; p = 0.004) were more likely seen in those with >50% SDH reduction. The mean fluoroscopy time was longer in patients with >50% SDH reduction compared to those with < 50% reduction (43.2 minutes vs. 28.2 minutes, respectively; p = 0.03). On linear regression analysis, history of hypertension showed a non‐significant trend towards < 50% resolution of SDH (OR 5.67; 95% CI 0.99, 32.43; p = 0.05). Femoral approach for MMA embolization was associated with >50% of hematoma reduction (OR 12.00; 95% CI 1.89, 76.38; p = 0.004). Longer fluoroscopy time showed the same association (OR 1.05, 95% CI 1.00, 1.11; p = 0.03). All‐cause mortality was seen in 6 of the 31 patients, none of them associated with the SDH or the n‐BCA embolization procedure with no significant difference between groups. Conclusions MMA embolization with n‐BCA appears to be an effective and safe method for management of SDH as has been shown in prior retrospective studies. Our small sample size may underestimate the effect some variables have on radiographic and clinical outcomes. Hypertension and use of AP seem to play a role in hematoma resolution; however, a bigger cohort is needed to confirm these hypotheses. Femoral approach and longer fluoroscopy time were associated with hematoma resolution, but other variables should be considered to rule out any procedure‐related confounders. Future randomized controlled trials may help establish MMA embolization as the primary method for SDH management given its safety and morbidity compared to traditional methods of SDH evacuation.

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.

Introduction Current published guidelines and meta‐analyses comparing direct mechanical thrombectomy (MT) alone versus MT with bridging intravenous thrombolysis (IVT) suggested that MT alone is non‐inferior to MT with bridging thrombolysis in achieving favorable functional outcome. Because of this controversy, we aimed to systematically update the evidence and meta‐analyze data from randomized trials comparing MT alone versus MT with bridging thrombolysis. Methods We searched MEDLINE (through Ovid), EMBASE, and the Cochrane Library from inception to December 14, 2021 without any language restrictions to identify randomized controlled trials (RCTs) and post‐hoc analyses of RCTs comparing direct MT with or without bridging IVT in patients presenting with acute ischemic stroke secondary to a large vessel occlusion. We conducted meta‐analyses using random‐effects models to compare the rates for favorable functional outcome (defined as modified Rankin scale [mRS] score of 0 to 2) and mortality at 90 days, and symptomatic intracranial hemorrhage (sICH), between MT and MT with IVT. We also assessed the risk of bias using the Cochrane risk‐of‐bias tool (RoB) and the certainty of evidence for each outcome using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Of 11,111 citations, we identified 53 eligible studies, and included 8 studies with a total of 3,008 participants. We found low‐certainty evidence suggesting that there is probably a small increase in the proportion of patients with favorable functional outcome with an mRS of 0 to 2 at 90 days for those who underwent MT with IVT compared to those with MT alone (risk ratio [RR] 1.08, 95% CI 0.99 to 1.19); moderate‐certainty evidence that there is probably a small decrease in mortality at 90 days for patients with MT plus IVT compared to MT alone (RR 0.86, 95% CI 0.71 to 1.03); and very low‐certainty evidence that there is possibly an increase in sICH for patients with MT plus IVT compared to MT alone (RR 1.17, 95% CI 0.85 to 1.61). When we restricted the analyses to RCTs only, we found no significant differences in favorable functional outcome (RR 2.05, 95% CI 0.97 to 1.13), mortality (RR 0.94, 95% CI 0.78 to 1.14), or sICH (RR 1.20, 95% CI 0.85 to 1.70). Conclusions Low‐certainty evidence shows that there is probably a small increase in the proportion of patients with favorable functional outcome, moderate‐certainty evidence shows that there is probably a small decrease in mortality, and very low‐certainty evidence that there is possibly an increase in sICH for patients with MT plus IVT compared to MT alone.