Endovascular Thrombectomy Trials Research Articles

Endovascular Thrombectomy for Acute Ischemic Stroke : Current Concept in Management.

Endovascular thrombectomy (EVT) has been established as the standard of care in the treatment of acute ischemic stroke (AIS) based on landmark randomized controlled trials. Nevertheless, while the strict eligibility of EVT for AIS patients restrict the wide application of EVT, a considerable population still undergoes off-label EVT. Besides, it is important to acknowledge that recanalization is not achieved in approximately 20% of procedures, and more than 50% of patients who undergo EVT still do not experience a favorable outcome. This article reviews the brief history of EVT trials and recent progressions in the treatment of AIS, with focusing on the expanding eligibility criteria, new target for EVT, and the evolution of EVT techniques.

Racial and Ethnic Diversity in Endovascular Thrombectomy Trials

The burden of acute ischemic stroke varies among racial and ethnic groups. Black adults face a higher incidence of stroke as well as higher rates of mortality. Thrombolytic therapy is under‐utilized in Black adults, and recent data show that endovascular thrombectomy is also under‐utilized for Black and Hispanic adults in the United States. Despite federal initiatives designed to promote the representation of diverse racial and ethnic groups in academic research, Black and Hispanic adults continue to be underrepresented in clinical trials conducted in the United States. Globally, the lack of standardization regarding race and ethnicity reporting makes it challenging to determine the overall diversity of trial enrollment. In this topical review, we provide an overview of racial and ethnic disparities in stroke incidence and clinical care with a focus on endovascular thrombectomy and follow this with a description of diversity reporting in endovascular thrombectomy trials. We conclude with opportunities for and barriers to increasing racial and ethnic diversity in endovascular thrombectomy trials.

June 2023 Stroke Highlights.

June 2023 Stroke Highlights.

B.6 Endovascular treatment of acute ischemic stroke in patients with pre-morbid disability: a meta-analysis

Background: Trials of endovascular thrombectomy (EVT) for acute stroke have excluded patients with pre-morbid disability. We performed a meta-analysis to assess the effectiveness and safety of EVT in patients with pre-morbid disability. Methods: According to PRISMA guidelines, we searched for studies describing outcomes in patients with pre-morbid disability (modified Rankin Scale [mRS] 2-5), treated with EVT or medical management (MM). Random-effects meta-analysis was used to pool outcomes including return to baseline mRS at 90 days, symptomatic ICH (sICH), and 90-day mortality. Results: We analyzed 14 studies of patients with pre-morbid disability (mRS2-5: EVT=1,373, MM=253). Compared to medical therapy, EVT was associated with higher likelihood of return to baseline mRS (OR=2.37, 95%CI:1.39-4.04) and a trend towards lower mortality (OR=0.68, 95%CI:0.46-1.02), with similar odds of sICH (OR 1.01, 95%CI:0.49-2.08). In studies comparing patients with vs. without pre-morbid disability treated with EVT, similar results were found except that pre-morbid disability, when defined more strictly as mRS 3-5, was associated with mortality (OR 3.49, p<0.001). Conclusions: In patients with pre-morbid disability, EVT carries a higher chance of return to baseline mRS compared to patients treated with MM or without pre-morbid disability, although with higher mortality than patients without pre-morbid disability. These findings merit validation with randomized controlled trials.

May 2022 Stroke Highlights

May 2022 <i>Stroke</i> Highlights

Cost-effectiveness of CT perfusion for patients with acute ischemic stroke (CLEOPATRA)-Study protocol for a healthcare evaluation study.

Computed tomography perfusion (CTP) is variably considered to assess eligibility for endovascular thrombectomy (EVT) in acute ischemic (AIS) stroke patients. Although CTP is recommended for patient selection in later (6-24 h) time window, it is currently not recommended in the earlier (0-6 h) time window and the costs and health effects of including CTP for EVT selection remain unknown. We aim to estimate the costs and health effects of using CTP for EVT selection in AIS patients compared to conventional selection. CLEOPATRA is a healthcare evaluation study using clinical and imaging data from multiple, prospective EVT trials and registries in both the earlier and later time windows. To study the long-term health and cost effects, we will construct a ("Markov") health state transition model simulating the clinical outcome over a 5-year follow-up period for CTP-based and conventional selection for EVT. Clinical data acquired within the current study and estimates from the literature will be used as input for probabilities of events, costs, and Quality-Adjusted Life Years (QALYs) per modified Rankin Scale (mRS) subscore. Primary outcome for the cost-effectiveness analysis will be the Incremental Cost-Effectiveness Ratio (ICER) in terms of costs per QALY gained over the simulated follow-up period. Outcome measures will be reported as cumulative values over a 5-year follow-up period. This study will provide preliminary insight into costs and health effects of including CTP in the selection for EVT for AIS patients, presenting between 0 and 24 h after time last known well. The results may be used to develop recommendations and inform further implementation projects and studies.

Successful thrombectomy is beneficial in patients with pre-stroke disability: Results from an international multicenter cohort study

BackgroundPatients with pre-stroke disability, defined as a modified Rankin Scale (mRS) ≥3, were excluded from most trials of endovascular thrombectomy (EVT) for acute stroke. We sought to evaluate the prognostic factors associated with favorable outcome in stroke patients with known disability undergoing EVT, and the impact of successful reperfusion. MethodsConsecutive acute stroke patients with pre-stroke disability, undergoing EVT, were retrospectively collected between 2016 to 2019 from a Canadian cohort and a multicenter French cohort (Endovascular Treatment in Ischemic Stroke registry-ETIS). Favorable outcome was defined as an mRS equal to pre-stroke mRS. Patients achieving successful reperfusion (defined as a modified Thrombolysis in Cerebral Infarction score of 2b/3) were compared with patients without successful reperfusion to determine if successful EVT was associated with better functional outcomes. ResultsAmong 6220 patients treated with EVT, 280 (4.5%) patients with a pre-stroke mRS ≥3 were included. Sixty-one patients (21.8%) had a favorable outcome and 146 (52.1%) died at 3 months. Patients with successful reperfusion had a higher proportion of favorable 90-day mRS (27.6% versus 19.6%, p = 0.025) and a lower mortality (48.3% versus 69.6%, p = 0.008) than patients without successful reperfusion. After adjusting for baseline prognostic factors, successful reperfusion defined by TICI ≥2b was associated with favorable functional outcome (OR 3.16 CI95% [1.11–11.5]; p 0.048). ConclusionIn patients with pre-stroke disability, successful reperfusion is associated with a greater proportion of favorable outcome and lower mortality.

Abstract TP75: LVO Screening Saves Lives

Background: Since publication of the landmark endovascular thrombectomy trials for large vessel occlusion (LVO) ischemic stroke patients, many clinical tools to identify these patients have been developed. In the real world, resource constraints may limit these early activation strategies. Definitive guidelines by the American Heart Association recommending LVO screening tools await studies proving their impact on outcome. We therefore aimed to evaluate the implementation of our LVO screening tool in our hospital on both time and clinical metrics. Methods: Our previously validated “SNO” scale (expressive aphasia/speech, neglect, ocular deviation), has acceptable balance of user ease, sensitivity and specificity. October 2020 we began an LVO alert for patients presenting with at least 1 of the 3 above signs, and collected their data including baseline National Institutes of Health Stroke scale scores (NIHSSS), time metrics, and mortality rates and compared them between LVO activation and non activation groups using t-test and chi square. Results: Since 10/2020, 93 (22 endovascularly treated) LVO alerts were called compared with 55 (23 treated) patients in the same time epoch who fulfilled criteria but not LVO activated (1219 stroke alerts called in 2020). Mean age was 71 vs 74 years and NIHSSS were 21 vs 18. There was a trend towards earlier minutes from door to puncture (94 vs 110), device placement (113 vs 129), and recanalization (146 vs 152) between them. The most significant difference was in door to thrombolysis times (33 vs 49 minutes, p&lt;0.03). Both groups had over 90% rate of successful recanalization. Discharge NIHSSS were not significantly different: 11 vs 9. There were more than twice the number of mortalities among the latter group (2 vs 5, p&gt;0.05). Discussion: Although LVO activation using SNO criteria has shortened times to intervention in our hospital, clinical improvements may be dampened by ongoing issues limiting full adoption. But, those treatment modalities that require no additional resources, regardless of LVO (IV TPA) were expedited. Conclusion: LVO activation based on SNO criteria has shortened time to treatment. NIHSSS at discharge did not notably improve among the LVO activation group, but in house mortality was halved.

P.063 Endovascular Treatment of Acute Ischemic Stroke in Patients with Pre-morbid Disability: A Meta-analysis

Background: Practice-changing trials of endovascular thrombectomy (EVT) for acute stroke excluded patients with pre-morbid disability. Observational studies may inform the role of EVT in this population. We performed a meta-analysis to estimate the effect of EVT in patients with pre-morbid disability. Methods: We adhered to PRISMA guidelines and searched Medline and Embase for studies describing EVT in adults with and without pre-morbid disability with stroke. Random-effects meta-analysis was used to pool outcomes, including favorable outcomes (mRS=0-2 or return to baseline), no increase in disability at 90 days, symptomatic ICH (sICH) and 90-day mortality. Results: We included 8 studies with 5570 patients (mRS 3-5=863, mRS 0-2=4,707). Patients with pre-morbid disability were more likely to return to their baseline mRS (aOR 2.53, 95% CI=1.47-4.36), although they had higher 90-day mortality (aOR=2.21, 95% CI=1.66-2.93). aOR for favorable outcome (aOR=0.83, 95% CI=0.67-1.03) or sICH (aOR=1.07, 95% CI=0.74-1.54) was not significantly different between groups. Conclusions: Observational studies suggest that EVT is safe in patients with pre-stroke disability and may result in comparable return to pre-stroke status as in patients without such disability. These findings argue against the routine exclusion of patients with pre-morbid disability from EVT and merit validation with randomized controlled trials.

Endovascular Treatment for Acute Stroke Patients With a Pre-stroke Disability: An International Survey.

Background: It is unclear what factors clinicians consider when deciding about endovascular thrombectomy (EVT) in acute ischemic stroke patients with a pre-existing disability. We aimed to explore international practice patterns and preferences for EVT in patients with a pre-stroke disability, defined as a modified Rankin score (mRS) ≥ 2.Methods: Electronic survey link was sent to principal investigators of five major EVT trials and members of a professional interventional neurology society.Results: Of the 81 survey-responding clinicians, 57% were neuro-interventionalists and 33% were non-interventional stroke clinicians. Overall, 64.2% would never or almost never consider EVT for a patient with pre-stroke mRS of 4-5, and 49.3% would always or almost always offer EVT for a patient with pre-stroke mRS 2-3. Perceived benefit of EVT (89%) and severity of baseline disability (83.5%) were identified as the most important clinician-level and patient-level factors that influence EVT decisions in these patients.Conclusion: In this survey of 80 respondents, we found that EVT practice for patients with pre-stroke disability across the world is heterogenous and depends upon patient characteristics. Individual clinician opinions substantially alter EVT decisions in pre-stroke disabled patients.

Abstract P589: Pediatric Thrombectomy: Design And Workflow Lessons From Two Experienced Centers

Introduction: While clinical trials have demonstrated the remarkable efficacy of endovascular thrombectomy (EVT) for treating adult patients suffering from acute ischemic stroke (AIS), benefits reaped from advances in adult stroke care have unfortunately not occurred in parallel with pediatric stroke care. Randomized trials of EVT in childhood stroke are unlikely given the low incidence of stroke in children compared to adults, and despite promising outcomes in small case reports and series, EVT in children remains an off-label procedure lacking established consensus guidelines. Along with a clear need to collect prospective pediatric EVT outcome data, there is a need to enhance pediatric stroke care infrastructure to provide high-quality care to children experiencing stroke. Methods: In this work, we review two successful pediatric thrombectomy programs, examining key workflow design features that are likely to be important for other programs that aspire to implement pediatric EVT capability. Discussion: While pediatric EVT workflows will vary between centers, we identify several key elements of programmatic success shared between the two reviewed stroke programs that may serve as foundational design considerations for centers aiming to develop their own pediatric EVT programs. These elements include a formalized protocol and workflow, integration with an adult EVT workflow, simplification and automation of workflow steps, pediatric adaptations of stroke imaging, advocacy of pediatric stroke care, and collaboration between providers, among others. These essential features transcend any single hospital environment and may provide an important foundation for other pediatric centers that aim to enhance the care of children with stroke. Conclusion: EVT shows promise in reducing stroke-associated morbidity in children. To maximize the efficacy of this intervention, workflow optimizations discussed here should be implemented by centers seeking to develop local pediatric EVT capability.

Endovascular thrombectomy in patients with large core ischemic stroke: a cost-effectiveness analysis from the SELECT study

BackgroundIt is unknown whether endovascular thrombectomy (EVT) is cost effective in large ischemic core infarcts.MethodsIn the prospective, multicenter, cohort study of imaging selection study (SELECT), large core was defined as...

283Endovascular thrombectomy as a means to improve survival in acute ischemic stroke - A meta-analysis

Abstract Background and purpose Although endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) is guideline-recommended to improve functional recovery, thus far there are only inconclusive data from underpowered singular trials of EVT vs. medical therapy (MT) on mortality. We here aimed to perform a meta-analysis on short-term mortality in guideline-relevant EVT vs. MT randomized controlled trials (RCTs). Methods All randomized controlled trials (RCT) reporting EVT vs. MT in the latest 2018 American Stroke Association/American Heart Association (ASA/AHA) Guidelines were eligible for inclusion. Data were abstracted by two independent investigators and double-checked by four others. Study data were integrated using the Cochran-Mantel-Haenszel method and a random-effects model to compute summary statistics of risk ratios (RR) with 95% confidence intervals (CI). Ninety-day mortality and intracranial hemorrhage (ICH) were analyzed. Results Ten of the twelve guideline-relevant EVT vs. MT RCTs (DAWN, DEFUSE 3, ESCAPE, EXTEND-IA, MR CLEAN, MR RESCUE, REVASCAT, SWIFT PRIME, THERAPY, THRACE) with 2,313 patients were selected for inclusion. Studies IMS III and SYNTHESIS were excluded due to their very infrequent use of EVT. Stent retrievers (Trevo, Solitaire, Merci) were most frequently applied, followed by thrombus aspiration (Penumbra). Intravenous thrombolysis was administered in addition to EVT in the majority of patients. In the pooled meta-analysis of all eligible RCTs, EVT significantly reduced the risk for 90-day mortality by 3.7% compared to MT (15.0% vs. 18.7%; RR 0.81 with CI 0.68 to 0.98; p=0.03), accounting for a number-needed-to-treat of 27 to prevent one all-cause death. Trends were similar in early-window (RR 0.83) and late-window trials only (RR 0.76). There was no difference in the risk for ICH in EVT vs. MT (4.2% vs. 4.0%; RR 1.11 with CI 0.71 to 1.72; p=0.65). All included trials were published in high-quality journals and risk of bias was judged low. Conclusions This meta-analysis lends evidence to EVT benefits for survival already during the first 90 days after acute ischemic stroke. These results further highlight the evolution of interventional techniques in this setting.

Abstract 111: Endovascular Thrombectomy May Be Safe and Effective in Patients With Large Core and Early Presentation

Background: Large infarct cores on CT or CTP were an exclusion from most trials of Endovascular thrombectomy (EVT). However, large cores may be seen in occasional patients presenting within the early window (0-3 hours) and may not preclude potential benefit from thrombectomy. We studied clinical outcomes with thrombectomy in patients presenting with large cores measured by CT or CTP within 3 hours of last known well (LKW). Methods: From a multicenter prospective cohort study of imaging selection for EVT (SELECT), patients with a large ischemic core (CBF&lt;30%) &gt; 50cc or ASPECT≤5 presenting within 3 hours from LKW to imaging were identified. All patients received CT and CTP with mismatch determination by RAPID software. A blinded independent core-lab adjudicated all images. Good (90 day mRS 0-2) and safety (sICH and mortality) outcomes were compared between patients who received EVT and those with medical management (MM) only. Results: Of 445 patients enrolled, 54 met criteria for large core and early presentation; 28 had ASPECT≤5 (17 EVT, 11 MM) and 40 had CTP &gt;50 cc (26 EVT, 14 MM) and 14 on both CT and CTP. Median (IQR) age 66 years (60, 75), NIHSS 20 (18, 23), LKW to puncture 162 min (range 69-343). Baseline characteristics were similar between EVT and MM. Patients with large core whether on CT (ASPECT≤5) or CTP (CBF&gt;50cc) had more frequent good outcome with EVT (30% overall, CT 35%, and CTP 27% vs 0% MM, p=0.04, Fig 1) Furthermore, EVT resulted in smaller average final infarcts (77 vs 202 ml, p=0.03), similar mortality (31% vs 29%, p=0.87) and sICH (16% vs 6%,p=0.34). In patients who achieved good outcome with thrombectomy, EVT resulted in smaller infarct growth 31 ml (10-58) vs 111 cc (67-233) in patients who had poor outcome, p=0.01. Outcome rates were similar if large core was defined as &gt;70ml. Conclusion: Patients with large core infarct measured by CT or CTP presenting within 3 hours may benefit from EVT. Time may trump imaging in patients with large core who present early.

Enlightenment and Challenges Offered by DAWN Trial (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo).

> Our greatest weakness lies in giving up. The most certain way to succeed is always to try just one more time (Science: A Collection of Quotes; Sapiens Hub 2017). > > —Thomas A. Edison (1847–1931) We are in a brand new era of acute stroke care led by 3 monumental achievements: (1) new reperfusion therapies, (2) expansion of the time window when there is still enough brain tissue to save, and (3) better understanding of the role of neuroimaging (eg, diffusion-weighted magnetic resonance imaging or perfusion computed tomographic use for decision-making in reperfusion therapies). The current management of acute ischemic stroke has only very recently dramatically changed with the publication of randomized trials using endovascular thrombectomy (EVT).1–4 Meta-analysis and pooled analysis from these trials consistently revealed an average 2.5×-fold reduction in disability (odds ratio, 2.49; 95% confidence interval, 1.76–3.53; P 300 minutes).2,5 As a result, physicians caring for acute stroke patients were given a brand new therapeutic arsenal but might also face more complex decisions (eg, stretching the benefits of EVT trials into real-world practice, subgroups with concomitant—and less investigated—comorbid conditions, time to transfer patients to a tertiary care institution, etc). Recent analysis showed a rapid decay of clinical benefit with EVT after 7.3 hours from the time of last seen well.6 Importantly, we learned about the identification of imaging patterns for patient selection that are associated with higher or lower likelihood of achieving a favorable outcome with reperfusion therapies (eg, collateral flow, …

Combining Neuroprotection With Endovascular Treatment of Acute Stroke: Is There Hope?

The goal of any clinical trial is to operationalize a paradigm in which the study enrolls the greatest proportion of responders in a setting that maximizes that study intervention’s treatment effect. Such a trial would have the most power to detect the therapeutic benefit it seeks to evaluate. Importantly, the trial should be grounded in—and consistent with—the pre-clinical science of the test intervention. Based on this, an acute ischemic stroke (AIS) trial must overcome the following 4 challenges: to have a design that conforms to that of animal studies that support the intervention, to minimize subject heterogeneity, to ensure that the treatment effect size is maximized, and to enroll subjects in the correct therapeutic window. Recent trials of endovascular thrombectomy (EVT)1–5 have decisively risen to this challenge for each of these aforementioned criteria: EVT recapitulates a wealth of animal studies demonstrating that stroke outcomes from temporary ischemia (eg, temporary middle cerebral artery occlusion [MCAO]) are better than in analogous animal models in which the MCAO is permanent. Subject heterogeneity in the recent EVT trials was reduced by selecting only those subjects who, on medical imaging, exhibit a large vessel occlusion (LVO). Selecting subjects with LVO also maximized the treatment effect size because untreated patients with LVO have a poorer prognosis even with tissue-type plasminogen activator (tPA) therapy,6–8 thus expanding the opportunity for EVT to provide a clinical benefit. Enrollment in the correct therapeutic window was achieved by optimizing the speed from diagnosis to reperfusion9 and, in some instances,1–3 by imaging criteria ensuring that enrolled patients still exhibited a penumbra. The success of recent EVT trials teaches that studies designed with the deliberate strategy of meeting these criteria may provide a better opportunity to demonstrate a clinical benefit than those that …

Abstract WP6: Real-World Data on Reperfusion: Evidence of Good Outcomes in the International Trevo Retriever Registry

Background: Endovascular thrombectomy trials established efficacy in acute ischemic stroke, yet real-world data on device effectiveness is warranted. Core lab adjudication of angiography is required to validate reperfusion, providing evidence and detailed data beyond randomized, controlled trials. We report the largest endovascular therapy registry data linking independent core lab data on reperfusion with clinical outcomes. Methods: The Trevo Retriever Registry is a prospective, open-label, consecutive enrollment, multicenter, international registry with more than 65 enrolling sites worldwide. An independent Imaging Core Lab, blind to all other data, evaluates the angiography with a battery of various TICI scores (mTICI, oTICI, oTICI2C) to define reperfusion. Statistical analyses examined TICI reperfusion and association with clinical outcomes considering expansive data collected in the registry. Results: 506 enrolled subjects (mean age 68.2 ± 14.2 yrs; 53% female) had core lab adjudicated angiography as of July 2016, including 21.5% &gt; 80 years old. Baseline NIHSS was median 15.0 (9.0, 20.0) with time from onset to CT of median 4.0 (1.7, 9.7) hrs. Core lab adjudicated arterial occlusion sites were: 53% M1, 24% ICA, 16% M2, 4% Basilar and 2% other. Time to reperfusion (oTICI ≥ 2A) was median 30.0 (19.0, 42.0) min. Core lab adjudicated revascularization was mTICI ≥ 2B in 90.4% (95%CI 87.4, 92.9), oTICI ≥ 2B in 82.3% (95%CI 78.6, 85.6) and oTICI2C ≥ 2C in 45.0% (95%CI 40.5, 49.6). mRS of 0-2 at 90 days was achieved in 57.3% (95%CI 52.5, 62.1). Extensive clinical, laboratory and stroke workflow variables were considered, yet only male sex (OR 0.62 (95% CI 0.38, 0.99) was an independent predictor of successful reperfusion (oTICI ≥ 2B) while age (OR 0.96 (95% CI 0.94, 0.97), NIHSS (OR 0.91 (95% CI 0.88, 0.94) and diabetes (OR 0.54 (95% CI 0.33, 0.88) predicted mRS 0-2 at 90 days. Conclusions: Proven reperfusion rates after endovascular stroke therapy excel in the real-world translation of thrombectomy devices around the globe, leading to good outcomes after stroke.

Imaging-based selection for revascularization in acute ischemic stroke.

With the positive results of recent endovascular thrombectomy (EVT) trials, intravenous thrombolysis (IVT) and EVT provide physicians with two majorly effective acute treatment options for patients with acute ischemic stroke. IVT and EVT can be used as a single treatment or as a combined IVT/EVT treatment approach. This review summarizes how imaging findings can help in selecting stroke patients who are likely to benefit from these revascularization therapies. IVT applied within 4.5 h from symptom onset remains the mainstay of acute stroke therapy and was also applied to most patients in the randomized EVT trials. Recent studies have failed to demonstrate the effectiveness of IVT in later time windows. Vascular imaging is crucial to identify patients with a target intracranial occlusion prior to EVT. Patients with a small ischemic core, with good leptomeningeal collaterals or with evidence of penumbral tissue may particularly benefit from EVT. These imaging findings may also identify patients who benefit from EVT if applied more than 6 h from symptom onset. Pretherapeutic imaging findings help in identifying stroke patients who are likely to benefit from endovascular stroke therapies, and may identify patients who benefit from revascularization therapies in later time windows.