Hardy, Nicole

Introduction Various clinical trials addressing large core acute ischemic stroke (AIS) are ongoing from multiple international groups. Future development of clinical guidelines depends on meta‐analyses of these trials calling for a degree of homogeneity of elements across the different studies. The aim of this common data element study was to provide an overview of the key features of pertinent large core infarct trials. Methods PubMed and ClinicalTrials.gov databases were screened for published and ongoing clinical trials assessing mechanical thrombectomy in patients with AIS with large core infarct. Nested Knowledge AutoLit living review platform was utilized to categorize primary and secondary outcomes as well as inclusion and exclusion criteria for patient selection in the clinical trials. Results The most reported data element was ASPECTS score, but with varied definitions of what compromises large core. Non‐utility‐weighted modified Rankin Score (mRS) was reported in 6/7 studies as the primary outcome, while the utility‐weighted mRS was the outcome of interest in the TESLA trial, all of them at the 3‐months mark, with only LASTE looking for mRS shift at the 6‐months mark. Secondary outcomes had more variations. Mortality is reported separately only in 4/7 trials, all at the 3‐month mark. Additionally, the TENSION trial reports the frequency of serious adverse events, including mortality, at the 1‐week and 12‐month mark. Conclusions In the published and the ongoing large core trials, there is a large degree of variability in the collected data elements. Differences in definition and timepoints renders reaching a unified standard difficult, which hinders high quality meta‐analyses and cohesive evidence‐driven synthesis.

Background Previous randomized controlled trials (RCTs) and meta-analyses were underpowered to demonstrate the superiority of endovascular thrombectomy (EVT) over medical therapy (MEDT) in the treatment of acute ischemic stroke due to large vessel occlusion of the posterior circulation (PC-LVO). We performed an updated systematic review and meta-analysis after the publication of the BAOCHE and ATTENTION trials to determine whether EVT can benefit patients presenting with PC-LVO. Methods Using Nested Knowledge, we screened literature for RCTs on EVT in PC-LVO. The primary outcome was 90-day modified Rankin Scale (mRS) score 0–3, and secondary outcomes included 90-day mRS score 0–2, 90-day mortality, and rate of symptomatic intracranial hemorrhage (sICH). A random-effects model was used to compute rate ratios (RRs) and their corresponding 95% confidence intervals (CIs). Results Four RCTs with 988 patients, 556 patients in the EVT arm and 432 patients in the MEDT arm, were included in the meta-analysis. EVT resulted in significantly higher rates of mRS score 0–3 (RR=1.54; 95% CI 1.16 to 2.04; P=0.002) and functional independence (RR=1.83; 95% CI 1.08 to 3.08; P=0.024), and lower rates of mortality (RR=0.76; 95% CI 0.65 to 0.90; P=0.002) at 90-day follow-up compared with MEDT alone. However, EVT patients had higher rates of sICH (RR=7.48; 95% CI 2.27 to 24.61; P<0.001). Conclusions EVT conferred significant patient benefit over MEDT alone in the treatment of PC-LVO. Future studies should better define patients for whom EVT is futile and determine factors that contribute to higher rates of sICH.

Background: New trials are planned regularly to provide the highest quality of evidence and invade new occlusion territories, which requires a pre-defined reporting strategy with consistent, common data elements for more straightforward collective evidence synthesis. We sought to review all active endovascular thrombectomy trials to investigate their patient selection criteria, intervention description, and reported outcomes. Methods: A literature search was systematically conducted on clinicaltrials.gov for active trials and all intervention, inclusion criteria, and outcomes reported were extracted. A qualitative synthesis of the frequency of study design types and data elements are graphically and narratively presented. Results: A total of 32 studies were tagged and included in the final qualitative analysis. The inclusion criteria were highly variable, including different cut-offs for the last well-known baseline National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and modified Rankin scale (mRS). Half of the studies (16/32) mentioned “thrombectomy” without defining which technique or device was used, and the final thrombolysis in cerebral infarction scale was provided in 19 (59.4%) studies. Heterogeneity was also present among the studies reporting a first-pass effect, both in how studies defined the outcome and in used ranges for mRS. Mortality and intracerebral hemorrhage (ICH) were more homogenous in their presentation and follow-up. Conclusions: There is a great degree of heterogeneity in the active thrombectomy trials concerning inclusion criteria, interventions used, and how outcomes are being reported.

Background The benefit of mechanical thrombectomy (MT) and efficacy of different first-line MT techniques remain unclear for distal and medium vessel occlusions (DMVOs). In this systematic review, we aimed to compare the performance of three first-line MT techniques in DMVOs. Methods The PubMed database was searched for studies examining the utility of MT in DMVOs (middle cerebral artery M2-3-4, anterior cerebral artery, and posterior cerebral artery). Studies providing data for aspiration thrombectomy (ASP), stent retriever thrombectomy (SR), and combined SR+ASP technique were included. Non-comparative studies were excluded. Safety and efficacy data were collected for each technique. The Nested Knowledge AutoLit platform was utilized for literature search, screening, and data extraction. Pooled data were presented as descriptive statistics. Results 13 studies comprising 2422 MT procedures were identified. The overall successful recanalization rate was 77.0% (1513/1964) for DMVOs. SR+ASP had a successful recanalization rate of 83.7% (297/355), SR had a 75.6% rate (638/844), while ASP alone had a 74.2% rate (386/520). The overall functional independence rate was 51.3% (851/1659) among DMVOs. The ASP alone group had a functional independence rate of 46.9% (219/467), while functional independence rates of the SR and SR+ASP groups were 51.5% (372/723) and 61.7% (174/282), respectively. Finally, the subarachnoid hemorrhage rates were 1.8% (4/217) for the ASP group, 9.3% (26/281) for the SR group, and 11.9% (41/344) for the SR+ASP group. Conclusions Our systematic review supports the proposition that MT is a safe and effective treatment option for DMVOs. Additionally, while the SR+ASP group had consistently high rates of clot clearance and good neurological outcomes, the SR and SR+ASP groups also had higher rates of subarachnoid hemorrhage, highlighting the need for improved DMVO treatment devices.

Background Endovascular thrombectomy (EVT) is an effective treatment for acute ischemic stroke attributable to the anterior circulation large‐vessel occlusion. Randomized trials of patients with posterior circulation large‐vessel occlusion (PC‐LVO) have failed to show a benefit of EVT over medical therapy (MEDT). We performed a systematic review and meta‐analysis to understand better whether EVT is beneficial for PC‐LVO. Methods Using the Nested Knowledge AutoLit living review platform, we identified randomized control trials and prospective studies that reported functional outcomes in patients with PC‐LVO treated with EVT versus MEDT. The primary outcome variable was 90‐day modified Rankin scale score of 0 to 3, and secondary outcome variables included 90‐day modified Rankin scale score of 0 to 2, 90‐day mortality, and rate of symptomatic intracranial hemorrhage. A separate random effects model was fit for each outcome measure to calculate pooled odds ratios. Results Three studies with 1248 patients, 860 in the EVT arm and 388 in the MEDT arm, were included in the meta‐analysis. The favorable outcome rate (modified Rankin scale score of 0–3) in patients undergoing EVT was 39.9% (95% CI, 30.6%–50.1%) versus 24.5% in patients undergoing MEDT (95% CI, 9.6%–49.8%). Patients undergoing EVT had higher modified Rankin scale score of 0 to 2 rates (31.8% [95% CI, 25.7%–38.5%] versus 19.7% [95% CI, 7.4%–42.7%]) and lower mortality (42.1% [95% CI, 35.9%–48.6%] versus 52.8% [95% CI, 33.3%–71.5%]) compared with patients undergoing MEDT, but neither result was statistically significant. Patients undergoing EVT were more likely to develop symptomatic intracranial hemorrhage (odds ratio, 10.36; 95% CI, 3.92–27.40). Conclusions EVT treatment of PC‐LVO trended toward superior functional outcomes and reduced mortality compared with MEDT despite a trend toward increased symptomatic intracranial hemorrhage in patients undergoing EVT. Existing randomized and prospective studies are insufficiently powered to demonstrate a benefit of EVT over MEDT in patients with PC‐LVO.

Background and Purpose: Endovascular thrombectomy (EVT) is an effective treatment for acute ischemic stroke (AIS) due to large vessel occlusion of the anterior circulation (AC-LVO). Randomized trials of posterior circulation large vessel occlusion (PC-LVO) patients have failed to show a benefit of EVT over medical therapy (MEDT). We performed a systematic review and meta-analysis to understand better whether EVT is beneficial for PC-LVO. Methods: Using the Nested Knowledge AutoLit living review platform, we identified randomized control trials and prospective studies that reported functional outcomes in patients with PC-LVO treated with EVT versus MEDT. The primary outcome variable was 90-day modified Rankin Scale (mRS) 0-3, and secondary outcome variables included 90-day mRS 0-2, 90-day mortality, and rate of symptomatic intracranial hemorrhage (sICH). A separate random effects model was fit for each outcome measure to calculate pooled odds ratios. Results: Three studies with 1,248 patients, 860 in the EVT arm and 388 in the MEDT arm, were included in the meta-analysis. The favorable outcome rate (mRS 0-3) in EVT patients was 39.9% (95% CI: 30.6-50.1%) versus 24.5% in MEDT patients (95% CI: 9.6-49.8%). EVT patients had higher mRS 0-2 rates (31.8% [95% CI: 25.7-38.5%] versus 19.7% [95% CI: 7.4-42.7%]) and lower mortality (42.1% [95% CI: 35.9-48.6%] versus 52.8% [95% CI: 33.3-71.5%]) compared to MEDT patients, but neither result was statistically significant. EVT patients were more likely to develop sICH (OR=10.36; 95% CI: 3.92-27.40). Conclusions: EVT treatment of PC-LVO trended toward superior functional outcomes and reduced mortality compared to MEDT despite a trend toward increased sICH in EVT patients. Existing randomized and prospective studies are insufficiently powered to demonstrate a benefit of EVT over MEDT in PC-LVO patients.