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. 2024 Mar 5;331(9):750-763.
doi: 10.1001/jama.2024.0572.

Endovascular Thrombectomy for Large Ischemic Stroke Across Ischemic Injury and Penumbra Profiles

Amrou Sarraj  1 , Ameer E Hassan  2 , Michael G Abraham  3 , Santiago Ortega-Gutierrez  4 , Scott E Kasner  5 , Muhammad Shazam Hussain  6 , Michael Chen  7 , Leonid Churilov  8 , Hannah Johns  8 , Clark W Sitton  9 , Vignan Yogendrakumar  8 , Felix C Ng  8 , Deep K Pujara  1 , Spiros Blackburn  9 , Sophia Sundararajan  1 , Yin C Hu  1 , Nabeel A Herial  10 , Juan F Arenillas  11 , Jenny P Tsai  12 , Ronald F Budzik  13 , William J Hicks  13 , Osman Kozak  14 , Bernard Yan  8 , Dennis J Cordato  15 , Nathan W Manning  15 , Mark W Parsons  15 , Andrew Cheung  15 , Ricardo A Hanel  16 , Amin N Aghaebrahim  16 , Teddy Y Wu  17 , Pere Cardona Portela  18 , Chirag D Gandhi  19 , Fawaz Al-Mufti  19 , Natalia Pérez de la Ossa  20 , Joanna D Schaafsma  21 , Jordi Blasco  22 , Navdeep Sangha  23 , Steven Warach  24 , Timothy J Kleinig  25 , Faris Shaker  9 , Faisal Al Shaibi  1 , Gabor Toth  6 , Mohammad A Abdulrazzak  6 , Gagan Sharma  8 , Abhishek Ray  1 , Jeffrey Sunshine  1 , Amanda Opaskar  1 , Kelsey R Duncan  1 , Wei Xiong  1 , Edgar A Samaniego  4 , Laith Maali  3 , Colleen G Lechtenberg  3 , Arturo Renú  22 , Nirav Vora  13 , Thanh Nguyen  26 , Johanna T Fifi  27 , Stavropoula I Tjoumakaris  10 , Pascal Jabbour  10 , Georgios Tsivgoulis  28 , Vitor Mendes Pereira  29 , Maarten G Lansberg  30 , Michael DeGeorgia  1 , Cathy A Sila  1 , Nicholas Bambakidis  1 , Michael D Hill  31 , Stephen M Davis  8 , Lawrence Wechsler  32 , James C Grotta  33 , Marc Ribo  34 , Greg W Albers  30 , Bruce C Campbell  8   35 ; SELECT2 Investigators
Collaborators, Affiliations

Endovascular Thrombectomy for Large Ischemic Stroke Across Ischemic Injury and Penumbra Profiles

Amrou Sarraj et al. JAMA. .

Abstract

Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain.

Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect.

Design, setting, and participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022.

Intervention: EVT vs MM.

Main outcomes and measures: Primary outcome was functional outcome-90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI.

Results: Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled.

Conclusion and relevance: In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased.

Trial registration: ClinicalTrials.gov Identifier: NCT03876457.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Sarraj reported receiving a research grant to institution from Stryker Neurovascular for the SELECT and SELECT2 trials during the conduct of the study. Dr Hassan reported receiving consulting fees from Medtronic, Microvention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt, Viz.ai, Insera Therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, Rapid Medical, Imperative Care, Galaxy Therapeutics, Route 92, and Perfuze during the conduct of the study. Dr Ortega Gutierrez reported receiving an investigator-initiated grant from Methinks for validation of the technology during the conduct of the study; receiving grants from the National Institutes of Health (NIH) (RO1 and RO3), Stryker Neurovascular (SEASE registry), Medtronic (DONE Symple trial), and Microventuion (Web off-label indications) outside the submitted work; and receiving consulting fees from Stryker Neurovascular (proctoring and educational lectures and conference talks) and Medtronic (educational lectures and conference talks). Dr Kasner reported receiving grants from Genentech, Diamedica, Daichii Sankyo, Bayer, and Gore outside the submitted work. Dr Hussain reported serving on the advisory board of Cerenovus Scientific; receiving personal fees from Stryker (data and safety monitoring board, EVOLVE study), RAPID Medical (clinical end point committee chair, DISTALS study); and receiving grants from Medtronic Core Lab (principal investigator for ADVANCE, INSPIRE, and VANTAGE studies) during the conduct of the study. Dr Herial reported serving as a consultant for Medtronic outside the submitted work. Dr Arenillas-Lara reported receiving grants from the Ministry of Science (Spain), AstraZeneca, Castilla y León Health Department, and the University of Valladolid Research Foundation and receiving personal fees from Medtronic, Boehringer-Ingelheim, Amgen, Bayer, Bristol Myers Squibb–Pfizer, Daichii-Sankyo, and AstraZeneca outside the submitted work. Dr Tsai reported receiving personal fees from Cerenovus, Microvention, Medtronic, Q’Apel, and Imperative Care outside the submitted work. Dr Hicks reported receiving personal fees from AstraZeneca outside the submitted work. Dr Manning reported receiving personal fees from Medtronic, Stryker, and Microvention outside the submitted work. Dr Cheung reported receiving personal fees from Medtronic and Penumbra outside the submitted work. Dr Hanel reported receiving personal fees from Medtronic, Stryker, Cerenovous, Balt, Phenox, Rapid Medical, and Q’Apel; receiving nonfinancial support from MiVI, eLum, Three Rivers Medical Inc, Shape Medical, and Corindus; receiving grants from the NIH, Interline Endowment, Microvention, Stryker, and CNX; and that he is investor/stockholder in InNeuroCo, Cerebrotech, eLum, EndoStream, Three Rivers Medical Inc, Scientia, RisT, BlinkTBI, Corindus, and NTI outside the submitted work. Dr Pérez de la Ossa reported receiving grants from Instituto de Salut Carlos III–RICORS ICTUS outside the submitted work. Dr Blasco reported receiving personal fees from Medtronic (clinical end point committee, Inspire Registry) outside the submitted work. Dr Warach reported receiving grants from University Hospitals Cleveland during the conduct of the study; receiving personal fees from Genentech (chair of data safety committee, TIMELESS trial) outside the submitted work. Dr Toth reported receiving consulting fees from Medtronic and Dynamed outside the submitted work. Dr Sunshine reported receiving grants from Siemens (magnetic resonance imaging development) outside the submitted work. Dr Nguyen reported serving on the advisory board for Idorsia and Brainomix outside the submitted work. Dr Fifi reported receiving personal fees from Stryker, Cerenovus, Microvention, MIVI, and Viz and stock ownership in Imperative Care outside the submitted work. Dr Tjoumakaris reported serving as a consultant for MicroVention outside the submitted work. Dr Pereira reported receiving personal fees from Stryker (principal investigator, Evolve study) outside the submitted work. Dr Sila reported receiving grants from Stryker during the conduct of the study. Dr Hill reported receiving grants from Boehringer-Ingelheim, NoNo Inc, Biogen Inc, Canadian Institutes of Health Research, and Alberta Innovates to the University of Calgary outside the submitted work; holding US Patent 62/086,077 licensed to Circle Ltd and US Patent 10,916,346 licensed to Circle Ltd; and serving as president of the Canadian Neurological Sciences Federation (not for profit) and board member for the Canadian Stroke Consortium (not for profit). Dr Davis reported receiving Australian government grants from the National Health and Medical Research Council and the Medical Research Future Fund; serving on advisory boards for Boehringer Ingelheim, CSL Behring, and Medtronic; and receiving lecture fees from Boehringer Ingelheim and Medtronic outside the submitted work. Dr Wechsler reported receiving personal fees from Athersys Inc outside the submitted work. Dr Ribo reported receiving personal fees from Anaconda Biomed, Medtronic, Methinks, Cerenovus, Philips, Nora Health, Apta Targets, and Rapid Pulse outside the submitted work. Dr Albers reported receiving personal fees from Genentech and iSchemaView and holding equity in iSchemaView. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Endovascular Thrombectomy Treatment Effect on mRS Score Distribution at 90-Day Follow-Up Across Various Imaging Strata, Reported Using Adjusted Generalized Odds Ratio
Treatment effect reported using adjusted generalized odds ratio (aGenOR), adjusted for age, National Institutes of Health Stroke Scale (NIHSS) score at presentation, time from last known well to randomization, and core volume. Core volume was not included as an adjustment covariate for analyses within core volume strata. aGenOR greater than 1 indicates better functional outcome (distribution of modified Rankin Scale [mRS] score) at 90-day follow-up with endovascular thrombectomy. The NIHSS is a 42-point scoring system measuring neurologic deficits, with higher score representing more neurologic deficits. The Alberta Stroke Program Early CT Score (ASPECTS) is a 10-point ordinal scoring system measuring areas of hypoattenuation due to ischemic changes in the middle cerebral artery territory on noncontrast computed tomography (CT) of the brain, with 1 point deducted for each location demonstrating hypoattenuation. Thus, lower scores represent worse ischemic injury. The CT perfusion/magnetic resonance imaging (MRI) core volume is a volumetric estimate obtained from CT perfusion using relative cerebral blood flow less than 30% threshold or MR diffusion imaging using apparent diffusion coefficient less than 620 × 10−6 mm/s2 threshold using automated RAPID-AI processing. The modified Rankin Scale (mRS) score is a 7-point ordinal scale measuring functional status, ranging from 0 (no residual deficit) to 6 (death).
Figure 2.
Figure 2.. Distribution of Modified Rankin Scale Score at 90-Day Follow-Up in the Study Population (Intention to Treat)
The modified Rankin Scale (mRS) score is a 7-point ordinal scale measuring functional status, ranging from 0 (no residual deficit) to 6 (death).
Figure 3.
Figure 3.. Association of Increasing CT Perfusion/MRI Core Volume and Functional Outcomes at 90-Day Follow-Up in Patients Receiving Endovascular Thrombectomy and Medical Management
The modified Rankin Scale (mRS) score is a 7-point ordinal scale measuring functional status, ranging from 0 (no residual deficit) to 6 (death). Panels A, B, and C illustrate estimated probability of mRS score 0-2, 0-3, and 5-6, respectively. Panel D illustrates the generalized odds of having an improvement of 1 point or more in mRS outcome as a function of computed tomography (CT) perfusion/magnetic resonance imaging (MRI) core volume.
See this image and copyright information in PMC

Comment in

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