Background Collateral blood flow markers have been associated with outcomes after thrombectomy in patients presenting with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Hypoperfusion intensity ratio (HIR), a metric reflecting tissue level collaterals, is one such marker with the potential to delineate patients who do and do not do well after thrombectomy. We determined if HIR correlated with successful reperfusion after thrombectomy. Methods Using Nested Knowledge, we screened literature for studies comparing patients with favorable versus unfavorable HIR, distinguished by a cutoff of 0.4, who underwent thrombectomy triage. The primary outcome was reperfusion success, as measured by thrombolysis in cerebral infarction ≥2b and secondary outcomes included rate of symptomatic intracranial hemorrhage, mortality at 90 days, and modified Rankin scale scores 0–2 at 90 days. A random effects model was used to compute pooled prevalence rates and their corresponding 95% confidence intervals (CI). Results Three studies with 973 patients, 496 with favorable HIR, and 477 with unfavorable HIR were included in this meta-analysis. The odds of reperfusion success were not significantly different between patients who had favorable versus unfavorable HIR (OR 0.96, 95% CI: 0.31–3.04) across two of the studies. Analysis of the remaining outcome variables was precluded by significant heterogeneity in data element reporting. Conclusions This meta-analysis was considerably limited by heterogeneity. Future meta-analyses on this topic, and other topics in the field of neurointervention would benefit from improved harmonization of study design and data element reporting.
Impact of branch arteries on efficacy of endoluminal flow diverters: Insights from posterior communicating artery aneurysms
Background Flow diverter treatment may inevitably require jailing of the branch vessels. While the patency of covered branch arteries and associated safety risks have been a topic of substantial interest, the question of whether the characteristics of branch vessels affect flow diversion's efficacy remains unanswered. In this study, we aimed to assess the impact of branch arteries on the efficacy of endoluminal flow diverters, specifically focusing on posterior communicating artery (Pcomm) aneurysms. Methods Following PRISMA guidelines, we systematically searched the MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane databases with predefined keywords. Studies providing data for flow diversion outcomes in Pcomm aneurysms were included. Outcomes of interest included complete and adequate aneurysm obliteration, ischemic and hemorrhagic complications, and Pcomm occlusion in the follow-up period. A random or fixed effects model was used to calculate the odds ratios (ORs) and pooled event rates with their corresponding confidence intervals (CI). Results The overall complete and adequate aneurysm occlusion rates were 72.25% (95% CI: 64.46–78.88%) and 88.37% (95% CI: 84.33–92.6), respectively. Fetal-type Pcomm aneurysms had significantly lower complete aneurysm occlusion rates than the nonfetal-type Pcomm aneurysms (OR: 0.12, 95% CI: 0.05–0.29). Overall ischemic and hemorrhagic complication rates were 2.62% (95% CI = 0.71–5.32) and 0.71% (95% CI: 0–2.24), respectively. There were no significant associations between Pcomm morphology and complications (OR: 3.61, 95% CI = 0.42–31.06 for ischemic complications and OR: 2.31, 95% CI = 0.36–14.6 for hemorrhage). Overall Pcomm occlusion rate was 32.04% (95% CI = 19.96–47.13), and the Pcomm patency was significantly lower in nonfetal-type Pcomm aneurysms (OR: 0.10, 95% CI = 0.02–0.44). Conclusion Our meta-analysis suggests that flow diversion is a safe treatment option for Pcomm aneurysms, regardless of fetal-type Pcomm morphology. However, on the other hand, our findings indicate that Pcomm anatomy or the presence of jailed large branches can affect the efficacy of flow diverter treatment.
Endovascular thrombectomy for ischemic stroke with large core volume: An updated, post-TESLA systematic review and meta-analysis of the randomized trials
Background Limited randomized controlled trials (RCTs) have been performed comparing endovascular thrombectomy (EVT) to medical therapy (MEDT) for acute ischemic stroke with extensive baseline ischemic injury (AIS-EBI). We conducted a systematic review and meta-analysis of RCTs reporting EVT for AIS-EBI. Methods Using the Nested Knowledge AutoLit software, we conducted a systematic literature review from inception to 12 February 2023 within Web of Science, Embase, Scopus, and PubMed databases. Results of the TESLA trial were included on 10 June 2023. We included RCTs that compared EVT to MEDT for AIS with large ischemic core volume. The primary outcome of interest was a modified Rankin Score (mRS) 0-2. Secondary outcomes of interest included early neurological improvement (ENI), mRS 0-3, thrombolysis in cerebral infarction (TICI) 2b-3, symptomatic intracranial hemorrhage (sICH), and mortality. A random-effects model was used to calculate risk ratios (RRs) and their corresponding 95% confidence intervals (CIs). Results We included four RCTs with 1310 patients, 661 of whom underwent EVT and 649 of whom were treated with MEDT. EVT was associated with greater rates of mRS 0-2 (RR = 2.33, 95% CI = 1.75–3.09; P -value < 0.001), mRS 0-3 (RR = 1.68, 95% CI = 1.33–2.12; P -value < 0.001), and ENI (RR = 2.24, 95% CI = 1.55–3.24; P -value < 0.001). Rates of sICH (RR = 1.99, 95% CI = 1.07–3.69; P -value = 0.03) were greater in the EVT group. Mortality (RR = 0.98, 95% CI = 0.83–1.15; P -value = 0.79) was comparable between the EVT and MEDT groups. The rate of successful reperfusion in the EVT group was 79.9% (95% CI = 75.6–83.6). Conclusions Although the rate of sICH was greater in the EVT group, EVT conferred a greater clinical benefit to MEDT for AIS-EBI based on available RCTs.
Effects of intravenous thrombolysis on stent retriever and aspiration thrombectomy outcomes: a systematic review and meta-analysis of the randomized controlled trials
Background Risks and benefits of intravenous thrombolysis (IVT) in patients undergoing mechanical thrombectomy (MT) have been a topic of interest. However, IVT’s specific effects on stent retriever (SR) and aspiration thrombectomy (ASP) outcomes remain largely unexplored. In this meta-analysis, we aimed to investigate the effects of IVT on SR and ASP thrombectomy outcomes. Methods In accordance with PRISMA guidelines, a systematic literature review was conducted using Medline, Embase, Scopus, Web of Science, and Cochrane Center of Clinical Trials databases. Outcomes of interest included successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b), modified first pass efficacy (mFPE), functional independence (modified Rankin Scale (mRS) ≤2), symptomatic intracranial hemorrhage (sICH), and embolization to new territories (ENT). Results Four randomized controlled trials with 1176 patients were included. SR and ASP resulted in similar mTICI ≥2b, mFPE, and mRS 0–2 rates in patients with and without IVT administration. SR without IVT was associated with a significantly lower rate of mFPE compared with the SR+IVT (RR 0.85, 95% CI 0.74 to 0.97). Furthermore, ASP without IVT resulted in a lower rate of mRS 0–2 than the ASP+IVT with a strong trend towards significance (RR 0.78, 95% CI 0.60 to 1.01). Finally, bridging therapy did not increase sICH and ENT rates after ASP or SR thrombectomy. Conclusions Our findings suggest that SR and ASP thrombectomy have comparable safety and efficacy profiles, regardless of prior IVT administration. Additionally, our results indicate that the addition of IVT may improve certain efficacy outcomes based on the employed first-line MT technique.
Endovascular Therapy for Stroke Presenting Beyond 24 Hours
ImportancePrevious randomized clinical trials (RCTs) have supported the use of endovascular therapy (EVT) in late-window acute ischemic stroke (AIS; 6-24 hours). However, little is known about the use of EVT in very late-window AIS (&gt;24 hours).ObjectiveTo examine outcomes following EVT for very late-window AIS.Data SourcesA systematic review of the English language literature was conducted using Web of Science, Embase, Scopus, and PubMed to search for articles published from database inception until December 13, 2022.Study SelectionThis systematic review and meta-analysis included published studies regarding very late-window AIS treated with EVT. Multiple reviewers screened studies, and an extensive manual search of the references of included articles was performed to identify any missed articles. Of the 1754 initially retrieved studies, 7 published between 2018 and 2023 were ultimately included.Data Extraction and SynthesisData were extracted independently by multiple authors and evaluated for consensus. Data were pooled using a random-effects model. This study is reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guideline, and the protocol was prospectively registered with PROSPERO.Main Outcomes and MeasuresThe primary outcome of interest was functional independence, as assessed with 90-day modified Rankin Scale (mRS) scores (0-2). Secondary outcomes included thrombolysis in cerebral infarction (TICI) scores (2b-3 or 3), symptomatic intracranial hemorrhage (sICH), 90-day mortality, early neurological improvement (ENI), and early neurological deterioration (END). Frequencies and means were pooled with the corresponding 95% CIs.ResultsThis review included 7 studies involving a total of 569 patients. The mean baseline National Institutes of Health Stroke Scale score was 13.6 (95% CI, 11.9-15.5), and the mean Alberta Stroke Program Early CT Score was 7.9 (95% CI, 7.2-8.7). The mean time from last known well and/or onset to puncture was 46.2 hours (95% CI, 32.4-65.9 hours). Frequencies for the primary and secondary outcomes were 32.0% (95% CI, 24.7%-40.2%) for functional independence (90-day mRS scores of 0-2) and 81.9% (95% CI, 78.5%-84.9%) for TICI scores of 2b to 3, 45.3% (95% CI, 36.6%-54.4%) for TICI scores of 3, 6.8% (95% CI, 4.3%-10.7%) for sICH, and 27.2% (95% CI, 22.9%-31.9%) for 90-day mortality. In addition, frequencies were 36.9% (95% CI, 26.4%-48.9%) for ENI and 14.3% (95% CI, 7.1%-26.7%) for END.Conclusions and RelevanceIn this review, EVT for very late-window AIS was associated with favorable frequencies of 90-day mRS scores of 0 to 2 and TICI scores of 2b to 3 and with low frequencies of 90-day mortality and sICH. These results suggest that EVT may be safe and associated with improved outcomes for very late-window AIS, although RCTs and prospective, comparative studies are needed to determine which patients may benefit from very late intervention.
Transradial balloon guide catheter placement for acute ischemic stroke thrombectomy: A systematic review and meta-analysis
Background Endovascular thrombectomy (EVT) is a treatment option for acute ischemic stroke due to large vessel occlusion. The use of a balloon-guided catheter (BGC) for EVT via transradial access (TRA) has emerged as a treatment approach, but its efficacy and safety compared to existing practices are uncertain. Methods A systematic literature review was performed using Embase, PubMed, Scopus, Web of Science databases, and manual search. Studies reporting safety and efficacy metrics for TRA BGC EVT were included. Data regarding recanalization time, thrombolysis in cerebral infarction (TICI), modified Rankin scale (mRS), symptomatic intracranial hemorrhage (sICH), first pass effect (FPE), and additional complications was pooled using a random-effects model to calculate event rates and 95% confidence intervals (CI). Results The search yielded five studies (n = 117). The mean time from puncture to final recanalization was 34.5 (95% CI = 30.5 to 39.14, I 2 = 0%, P-value = 0.37) min. Successful recanalization (TICI 2b-3) and complete recanalization (TICI 3) occurred in 96.6% (95% CI = 91.24 to 98.71, I 2 = 0%, P-value = 0.99) and 55.2% (95% CI = 42.14 to 67.54, I 2 = 0%, P-value = 0.39) of cases, respectively. FPE occurred in 67.5% (95% CI = 51.73 to 80.10, I 2 = 0%, P-value = 0.56) of patients. mRS 0-2 was achieved in 41.2% (95% CI = 27.34 to 56.65, I 2 = 70%, P-value = 0.07) of patients. sICH occurred in 5.0% (95% CI = 1.25 to 17.91, I 2 = 0%, P-value = 1.00) of patients. Local complications of radial hematoma and radial vasospasm occurred in 5.0% (95% CI = 0.49 to 12.36, I 2 = 29%, P-value = 0.24) and 2.1% (95% CI = 1.25 to 17.91, I 2 = 71%, P-value = 0.03) of cases, respectively. Switch to femoral access was necessary in 3.7% (95% CI = 0.00 to 14.07, I 2 = 68%, P-value = 0.02) of procedures. The average number of passes per procedure was 1.6 (95% CI = 1.15 to 2.11, I 2 = 88%, P-value < 0.001). Conclusion TRA BGC EVT has potential as a safe and efficacious treatment option compared to existing methods. However, additional, prospective studies are necessary to inform clinical decision making.
Abstract Number ‐ 95: Common Data Elements Analysis of Mechanical Thrombectomy Clinical Trials for Acute Ischemic Large Core Stroke
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.
The safety profile of single antiplatelet therapy with flow diverters: Systematic review and meta-analysis
Background Dual antiplatelet therapy (DAPT) is frequently used in treating cerebral aneurysms with flow diverters (FDs), whereas single antiplatelet therapy (SAPT) is used mostly with coated FDs and in ruptured aneurysms. We conducted a systematic review and meta-analysis to explore the safety profile of SAPT in FDs. Methods PubMed, Web of Science, OVID Embase, OVID Medline, and Scopus were searched to 1st November 2022. Outcomes of interest included ischemic and hemorrhagic complications, conversion to DAPTs, and in-stent stenosis rates under long-term SAPT. SAPT is divided into aspirin (ASA) vs. non-ASA group (ticagrelor or prasugrel). Subgroup analysis was performed for ruptured vs. non-ruptured aneurysms and coated vs. non-coated FDs. All data were analyzed using R software version 4.2.2. Results Twelve studies with 240 total patients (43 patients in the ASA group and 197 patients in the non-ASA group) were included in our meta-analysis. The pooled ischemic occlusion rate was 9.8% (95% CI = 4.87−18.95: p-value = 0.09) for SAPTs. The ASA group had significantly higher ischemic complication rates compared to the non-ASA group (20.8% vs. 6.3%, respectively, p-value = 0.02). The pooled hemorrhagic complication rate was 3.5% (95% CI = 1.38−8.81: p-value > 0.99). The hemorrhagic rates of ASA group were 9.3%% (95% CI = 3.54−22.30) over the non-ASA group 2.1% (95% CI = 0.58−7.54) ( p-value > 0.99). The overall in-stent stenosis rate was 2.3% (95% CI = 1.06−5.14: p-value > 0.99). The ischemic complication rates were comparable between coated vs non-coated FDs (10.7% vs. 5.5% p-value = 0.39). In stent stenosis rate were 1.9% (95% CI = 0.72−4.96) in coated FDs over 4.4% (95% CI = 1.11−16.11) ( p-value = 0.32). The ruptured and non-ruptured groups also showed comparable results in terms of ischemic (17.6% vs. 7.1% respectively, p-value = 0.24) and hemorrhagic complications (9.8% vs. 1.1%, respectively, p-value = 0.08). Conclusions Flow diverter treatment under ASA monotherapy resulted in relatively high ischemic complication rates. However, SAPT with prasugrel or ticagrelor monotherapy is promising for coated FDs and ruptured aneurysm treatments. Given the overall small sample size and also the likely presence of known and unknown biases regarding choice of antiplatelet therapy between groups, larger cohort studies are needed to evaluate SAPT treatment outcomes.
National Institutes of Health grant funding for cerebrovascular diseases
Background Federal research funding is highly sought after but may be challenging to attain. A clear understanding of funding for specific diseases, such as cerebrovascular disorders, might help researchers regarding which National Institutes of Health (NIH) institutes fund research into specific disorders and grant types. Objective To examine the current scope of NIH grant funding for cerebrovascular conditions. Methods The NIH-developed RePORTER was used to extract active NIH-funded studies related to cerebrovascular diseases through January 2023. Duplicate studies were removed, and projects were manually screened and labeled in subcategories as clinical and basic science and as research subcategories. Extracted data included total funding, grant types, institutions that received funding, and diseases studied. Python (version 3.9) and SciPy library were used for statistical analyses. Results We identified 1232 cerebrovascular projects across seven diseases with US$699 952 926 in total funding. The cerebrovascular diseases with the greatest number of grants were ischemic stroke (705, or 57.2% of all funded projects), carotid disease (193, or 15.7%), and hemorrhagic stroke (163, or 13.2%). R01 grants were the most common mechanism of funding (632 grants, or 51.3%). The National Institute of Neurological Disorders and Stroke (NINDS) funded the most projects (504 projects; US$325 536 405), followed by the National Heart, Lung, and Blood Institute (NHLBI) (376 projects; US$216 784 546). Conclusion Cerebrovascular disease receives roughly US$700 million in NIH funding. Ischemic stroke accounts for the majority of NIH-funded cerebrovascular projects, and R01 grants are the most common funding mechanism. Notably, NHLBI provides a large proportion of funding, in addition to NINDS.
Mechanical thrombectomy with Q catheter in stroke caused by primary and secondary distal and medium vessel occlusions
Background The MIVI Q aspiration catheters have been shown to achieve significantly greater flow rates than other intracranial aspiration catheters in vitro. We describe our initial real-world experience with the MIVI Q catheter in emergent acute ischemic stroke (AIS) caused by distal and medium vessel occlusions (DMVO). Methods Data was collated from a prospectively maintained database which included patients from October 2019 to December 2022. Occlusion demographics, thrombectomy technique, reperfusion scoring, procedural complications and disposition were assessed. The primary outcome of interest was rate of successful reperfusion defined as thrombolysis in cerebral infarction (TICI) score 2b-3. Secondary outcomes included rate of first pass effect (FPE) and complications. Results We included 64 target occlusions in 51 patients. The Q catheter successfully reached the DMVO in all occlusions. Successful reperfusion was achieved in 49/64 (76.6%) occlusions, and TICI scores were similar for primary and secondary DMVOs (P value = 0.41). FPE was achieved in 39/64 (60.9%) occlusions and did not differ between primary and secondary DMVOs (P value = 0.13). Reperfusion hemorrhage occurred in 3/64 (4.7%) cases, small volume subarachnoid hemorrhage in 3/64 (4.7%) cases, and small hemorrhagic transformation in 1/64 (1.6%) cases; the rate of complications did not differ based on primary versus secondary DMVO (P value = 0.29). Conclusion The MIVI Q catheter is both safe and effective. Our real-world experience supports the superior flow rates demonstrated in vitro and translates into high rates of successful reperfusion in AIS caused by DMVO in clinical practice.