Background Direct mechanical thrombectomy (dMT) may result in similar outcomes compared to a bridging approach with intravenous thrombolysis (IVT+MT) in acute ischaemic stroke. Recent randomised controlled trials (RCTs) have varied in their design and non-inferiority margins (NIM). Aim We sought to meta-analyse accumulated trial data to assess the difference and non-inferiority in clinical and procedural outcomes between dMT and bridging therapy. Summary of review We conducted a systematic review of electronic databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Random effects meta-analyses were conducted for the pooled data. The primary outcome was good functional outcome at 90 days (modified Rankin Scale (mRS)≤2). Secondary outcomes included excellent functional outcome (mRS≤1), mortality, any intracranial haemorrhage (ICH), symptomatic ICH, successful reperfusion (TICI2b) and procedure-related complications. Four RCTs comprising 1633 patients (817 dMT, 816 bridging therapy) were included. There were no statistical differences for the 90-day good functional outcome (OR=1.02, 95%CI 0.84-1.25, p=0.54, I2=0%), and the absolute risk difference was 1% (95% CI −4% to 5%). The lower 95% CI falls within the strictest NIM of -10% among included RCTs. dMT reduced the odds of successful reperfusion (OR=0.76, 95%CI 0.60-0.97, p=0.03, I2=0%) and any ICH (OR=0.65, 95%CI 0.49-0.86, p=0.003, I2=38%). There was no difference in the remaining secondary outcomes. The risk of bias for all studies was low. Conclusion The combined trial data assessing dMT versus bridging therapy showed no difference in improving good functional outcome. The wide non-inferiority thresholds set by individual trials are in contrast with the clinical consensus on minimally important differences. However, our pooled analysis indicates non-inferiority of dMT with a 4% margin of confidence. The application of these findings is limited to patients presenting directly to MT-capable centres and real-world workflow times may differ against those achieved in a trial setting.

Background: The impact on clinical outcomes of patient selection using perfusion imaging for endovascular thrombectomy (EVT) in patients with acute ischemic stroke presenting beyond 6 hours from onset remains undetermined in routine clinical practice. Methods: Patients from a national stroke registry that underwent EVT selected with or without perfusion imaging (noncontrast computed tomography/computed tomography angiography) in the early (<6 hours) and late (6–24 hours) time windows, between October 2015 and March 2020, were compared. The primary outcome was the ordinal shift in the modified Rankin Scale score at hospital discharge. Other outcomes included functional independence (modified Rankin Scale score ≤2) and in-hospital mortality, symptomatic intracerebral hemorrhage, successful reperfusion (Thrombolysis in Cerebral Infarction score 2b–3), early neurological deterioration, futile recanalization (modified Rankin Scale score 4–6 despite successful reperfusion) and procedural time metrics. Multivariable analyses were performed, adjusted for age, sex, baseline stroke severity, prestroke disability, intravenous thrombolysis, mode of anesthesia (Model 1) and including EVT technique, balloon guide catheter, and center (Model 2). Results: We included 4249 patients, 3203 in the early window (593 with perfusion versus 2610 without perfusion) and 1046 in the late window (378 with perfusion versus 668 without perfusion). Within the late window, patients with perfusion imaging had a shift towards better functional outcome at discharge compared with those without perfusion imaging (adjusted common odds ratio [OR], 1.45 [95% CI, 1.16–1.83]; P =0.001). There was no significant difference in functional independence (29.3% with perfusion versus 24.8% without; P =0.210) or in the safety outcome measures of symptomatic intracerebral hemorrhage ( P =0.53) and in-hospital mortality (10.6% with perfusion versus 14.3% without; P =0.053). In the early time window, patients with perfusion imaging had significantly improved odds of functional outcome (adjusted common OR, 1.51 [95% CI, 1.28–1.78]; P =0.0001) and functional independence (41.6% versus 33.6%, adjusted OR, 1.31 [95% CI, 1.08–1.59]; P =0.006). Perfusion imaging was associated with lower odds of futile recanalization in both time windows (late: adjusted OR, 0.70 [95% CI, 0.50–0.97]; P =0.034; early: adjusted OR, 0.80 [95% CI, 0.65–0.99]; P =0.047). Conclusions: In this real-world study, acquisition of perfusion imaging for EVT was associated with improvement in functional disability in the early and late time windows compared with nonperfusion neuroimaging. These indirect comparisons should be interpreted with caution while awaiting confirmatory data from prospective randomized trials.

BackgroundThe optimal anesthetic modality for endovascular treatment (EVT) in acute ischemic stroke (AIS) is undetermined. Comparisons of general anesthesia (GA) with composite non-GA cohorts of conscious sedation (CS) and local anesthesia (LA) without sedation have provided conflicting results. There has been emerging interest in assessing whether LA alone may be associated with improved outcomes. We conducted a systematic review and meta-analysis to evaluate clinical and procedural outcomes comparing LA with CS and GA.MethodsWe reviewed the literature for studies reporting outcome variables in LA versus CS and LA versus GA comparisons. The primary outcome was 90 day good functional outcome (modified Rankin Scale (mRS) score of ≤2). Secondary outcomes included mortality, symptomatic intracerebral hemorrhage, excellent functional outcome (mRS score ≤1), successful reperfusion (Thrombolysis in Cerebral Infarction (TICI) >2b), procedural time metrics, and procedural complications. Random effects meta-analysis was performed on unadjusted and adjusted data.ResultsEight non-randomized studies of 7797 patients (2797 LA, 2218 CS, and 2782 GA) were identified. In the LA versus GA comparison, no statistically significant differences were found in unadjusted analyses for 90 day good functional outcome or mortality (OR=1.22, 95% CI 0.84 to 1.76, p=0.3 and OR=0.83, 95% CI 0.64 to 1.07, p=0.15, respectively) or in the LA versus CS comparison (OR=1.14, 95% CI 0.76 to 1.71, p=0.53 and OR=0.88, 95% CI 0.62 to 1.24, p=0.47, respectively). There was a tendency towards achieving excellent functional outcome (mRS ≤1) in the LA group versus the GA group (OR=1.44, 95% CI 1.00 to 2.08, p=0.05, I2=70%). Analysis of adjusted data demonstrated a tendency towards higher odds of death at 90 days in the GA versus the LA group (OR=1.24, 95% CI 1.00 to 1.54, p=0.05, I2=0%).ConclusionLA without sedation was not significantly superior to CS or GA in improving outcomes when performing EVT for AIS. However, the quality of the included studies impaired interpretation, and inclusion of an LA arm in future well designed multicenter, randomized controlled trials is warranted.

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BackgroundThe effectiveness and safety of endovascular thrombectomy (EVT) in the late window (6–24 hours) for acute ischemic stroke (AIS) patients selected without advanced imaging is undetermined. We aimed to assess clinical outcomes and the relationship with time-to-EVT treatment beyond 6 hours of stroke onset without advanced neuroimaging.MethodsPatients who underwent EVT selected with non-contrast CT/CT angiography (without CT perfusion or MR imaging), between October 2015 and March 2020, were included from a national stroke registry. Functional and safety outcomes were assessed in both early (<6 hours) and late windows with time analyzed as a continuous variable.ResultsAmong 3278 patients, 2610 (79.6%) and 668 (20.4%) patients were included in the early and late windows, respectively. In the late window, for every hour delay, there was no significant association with shift towards poorer functional outcome (modified Rankin Scale (mRS)) at discharge (adjusted common OR 0.98, 95% CI 0.94 to 1.01, p=0.27) or change in predicted functional independence (mRS ≤2) (24.5% to 23.3% from 6 to 24 hours; aOR 0.99, 95% CI0.94 to 1.04, p=0.85). In contrast, predicted functional independence was time sensitive in the early window: 5.2% reduction per-hour delay (49.4% to 23.5% from 1 to 6 hours, p=0.0001). There were similar rates of symptomatic intracranial hemorrhage (sICH) (3.4% vs 4.6%, p=0.54) and in-hospital mortality (12.9% vs 14.6%, p=0.33) in the early and late windows, respectively, without a significant association with time.ConclusionIn this real-world study, there was minimal change in functional disability, sICH and in-hospital mortality within and across the late window. While confirmatory randomized trials are needed, these findings suggest that EVT remains feasible and safe when performed in AIS patients selected without advanced neuroimaging between 6–24 hours from stroke onset.

<b><i>Background:</i></b> Recent reports have suggested that atrial fibrillation (AF) is more prevalent in the large vessel occlusion (LVO) subgroup of acute ischaemic stroke patients. Given the association between left atrial enlargement (LAE) and AF, we sought to evaluate the feasibility of assessing LAE on non-gated CT and its association with LVO in the hyperacute stroke setting. <b><i>Methods:</i></b> We analysed our prospectively collected database that included all stroke patients referred for consideration of endovascular treatment between April 14, 2020, and May 21, 2020. During this period, a CT chest was included in our regional stroke protocol to aid triage of patients suspected for COVID-19 from which cardiac measurements were obtained. Patients were dichotomized into LVO and no-LVO groups, and LA measurements were trichotomized into normal, borderline, and enlarged. Univariate analyses were performed between groups. <b><i>Results:</i></b> Of the included 38 patients, 21 were categorized as LVO and 17 as no LVO. There was a statistically significant association between LAE and LVO (<i>p</i> = 0.028). No significant difference was demonstrated between groups for the baseline AF and other clinical characteristics, except for baseline NIHSS (<i>p</i> = 0.0005). There was excellent inter- and intra-rater reliability (ICC = 0.969) for LA measurements. <b><i>Conclusion:</i></b> Our study provides preliminary data to suggest LAE is more prevalent in the LVO stroke subgroup at presentation and can be reliably assessed on non-gated CT in the hyperacute setting. These findings have potential implications for stratifying secondary management and may prompt a more rigorous pursuit of occult AF or other cardiac causes of stroke.

BACKGROUND The safety and efficacy of endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large vessel occlusion presenting beyond 24 hours from last known well (LKW) remains undetermined. METHODS In this single center study, we identified patients with large vessel occlusion who were eligible for EVT based on noncontrast computed tomography (CT)/CT angiography (without CT perfusion or magnetic resonance imaging) using an Alberta Stroke Program Early CT Score of ≥5, National Institutes of Health Stroke Scale of ≥6, and presenting beyond 24 hours from LKW, between January 2018 and March 2022. During the study period, EVT service limitations meant patients eligible for EVT presenting outside service hours, routinely received best medical management (BMM). Functional and safety outcomes were compared between patients receiving EVT or BMM following multivariable adjustment for age, baseline stroke severity, Alberta Stroke Program Early CT Score, time from LKW, IV thrombolysis, and clot location. RESULTS Among 35 patients presenting beyond 24 hours from LKW and eligible for EVT, 19 (54%) were treated with EVT and 16 (46%) with BMM. Alberta Stroke Program Early CT Score were similar across both groups (EVT: 7 [6.75–8] versus BMM: 7 [6–8]), but not the baseline National Institutes of Health Stroke Scale (EVT: 17 [11–19.5] versus BMM: 20 [9.75–26]). No significant difference was observed between the EVT and BMM groups in the symptomatic intracranial hemorrhage (5.3% versus 0%; P =0.28) or mortality (26.3% versus 37.5%; P =0.42) rates, respectively. The modified Rankin scale at 90 days (adjusted common odds ratio [OR], 1.94; [95% CI 0.42–8.87]; P =0.39) and functional independence rate, although numerically higher in the EVT group compared with the BMM group (modified Rankin scale≤2; 36.9% versus 18.8%; adjusted OR, 4.34; [95% CI 0.34–54.83]; P =0.25), were not significantly different. 94.7% of patients treated with EVT achieved successful reperfusion (modified thrombolysis in cerebral infarction 2b–3). CONCLUSION In routine clinical practice, EVT beyond 24 hours from LKW appears safe and feasible, when performed in patients with acute ischemic stroke who were deemed eligible for EVT by noncontrast CT /CT angiography alone. A large collaborative randomized trial assessing the efficacy of EVT beyond 24 hours is warranted. Our findings provide a basis for the sample size estimate for an adequately powered trial.

BACKGROUND The efficacy and safety of endovascular thrombectomy (EVT) >6 hours from acute ischemic stroke (AIS) onset for patients selected without computed tomography (CT) perfusion or magnetic resonance imaging is undetermined in routine clinical practice. METHODS In this single‐center study, we identified consecutive late‐presenting patients with AIS who were eligible for EVT on the basis of noncontrast CT/CT angiography (without CT perfusion or magnetic resonance imaging) using an Alberta Stroke Program Early CT Score of ≥6, >6 hours from stroke onset, between January 2018 and March 2022. During the study period, EVT capacity limitations meant EVT‐eligible patients presenting out of regular working hours, consistently received best medical management (BMM). Functional outcomes (modified Rankin Scale at 90 days), symptomatic intracranial hemorrhage, and mortality at 90 days were compared between patients receiving EVT or BMM following multivariable adjustment for age, sex, baseline stroke severity, Alberta Stroke Program Early CT Score, onset‐to‐neuroimaging time, intravenous thrombolysis, and clot location. RESULTS Among 4802 patients with AIS, 150 patients (3.1%) presenting beyond 6 hours of onset were eligible for EVT: 74 (49%) treated with EVT and 76 (51%) with BMM. Compared with the BMM group, patients treated with EVT had significantly improved functional outcome (modified Rankin Scale) (adjusted common odds ratio, 2.23 [95% CI, 1.18–4.22]; P =0.013), and higher rates of functional independence (modified Rankin Scale ≤2; 39.2.% versus 9.2%; adjusted odds ratio, =4.73 [95% CI, 1.64–13.63]; P =0.004). No significant difference was observed between the EVT and BMM groups in the symptomatic intracranial hemorrhage (5.4% versus 2.6%; P =0.94) or mortality (20.2% versus 47.3%; P =0.16) rates, respectively. CONCLUSION In routine clinical practice, of the 3.1% of patients in our AIS population presenting after 6 hours from stroke onset who were deemed eligible for EVT by noncontrast CT/CT angiography alone, those treated with EVT achieved significantly improved functional outcome, compared with patients treated with BMM only. No significant differences were noted between the 2 groups with respect to symptomatic intracranial hemorrhage and mortality. While confirmatory randomized trials are awaited, these findings suggest that EVT is effective and safe when performed in patients with AIS selected without CT perfusion or magnetic resonance imaging >6 hours from stroke onset.