Endovascular Thrombectomy for Large Ischemic Stroke Across Ischemic Injury and Penumbra Profiles
Authors: Sarraj Amrou , Hassan Ameer E. , Abraham Michael G. , Ortega-Gutierrez Santiago , Kasner Scott E. , Hussain Muhammad Shazam , Chen Michael , Churilov Leonid , Johns Hannah , Sitton Clark W. , Yogendrakumar Vignan , Ng Felix C. , Pujara Deep K. , Blackburn Spiros , Sundararajan Sophia , Hu Yin C. , Herial Nabeel A. , Arenillas Juan F. , Tsai Jenny P. , Budzik Ronald F. , Hicks William J. , Kozak Osman , Yan Bernard , Cordato Dennis J. , Manning Nathan W. , Parsons Mark W. , Cheung Andrew , Hanel Ricardo A. , Aghaebrahim Amin N. , Wu Teddy Y. , Portela Pere Cardona , Gandhi Chirag D. , Al-Mufti Fawaz , Pérez de la Ossa Natalia , Schaafsma Joanna D. , Blasco Jordi , Sangha Navdeep , Warach Steven , Kleinig Timothy J. , Shaker Faris , Al Shaibi Faisal , Toth Gabor , Abdulrazzak Mohammad A. , Sharma Gagan , Ray Abhishek , Sunshine Jeffrey , Opaskar Amanda , Duncan Kelsey R. , Xiong Wei , Samaniego Edgar A. , Maali Laith , Lechtenberg Colleen G. , Renú Arturo , Vora Nirav , Nguyen Thanh , Fifi Johanna T. , Tjoumakaris Stavropoula I. , Jabbour Pascal , Tsivgoulis Georgios , Pereira Vitor Mendes , Lansberg Maarten G. , DeGeorgia Michael , Sila Cathy A. , Bambakidis Nicholas , Hill Michael D. , Davis Stephen M. , Wechsler Lawrence , Grotta James C. , Ribo Marc , Albers Greg W. , Campbell Bruce C. ,   SELECT2 Investigators, Sarraj Amrou , Sundararajan Sophia , Hu Yin , Sila  Cathy , Furlan  Anthony , Opaskar  Amanda , Bambakidis  Nicholas , Ray  Abhishek , Sunshine  Jeffrey , DeGeorgia Michael , Xiong Wei , Duncan  Rose , Fadhil  Ali , Hansen John , Patel Mohit , Chugh Arunit , Al-Shaibi Faisal , Alomar Majed , El-Azzouni Soheil , Moussa Rami B , Jin Dasul , Nayak Katrina M , Zhang Yiyi , Modak Nikhil S , Jumah Muruj M , Liou Deng-Yuan Dean , Alamoudi Abdullah , Pujara Deep , Blackburn Spiros , Grotta James C. , Sitton Clark , Rahbar Mohammad H , Dannenbaum  Mark , Riascos Roy , Spiegel  Gary , Barreto  Andrew , Sharieff  Anjail , Cochran  Joseph , Day  Arthur L. , Gonzales  Nicole , Reddy  Sujan , Fournier  Lauren , Jones  Erica M , Zelini  Pamela , Kamal  Haris , Castanon Felix  Guerra , Asim Naveed , Shaker Faris , Hessabi Manouchehr , Tahanan Amirali , Abraham Michael , Maali Laith , Ebersole  Koji , Kawano  Jorge , Lechtenberg  Colleen , Slavin  Sabreena , Maali  Latih , Madarang  Ernest , Pendurthi  Aparna , Qureshi  Abid , Reeves  Alan , Rosterman  Lee , Wang  Yunxia , Barkley  Tiffany Thu , Vanguru  Husitha , Paterson  Jeremy , Walters  Carissa , Ackerman  Peyton , Hanel Ricardo , Aghaebrahim Amin N , Sauvageau  Eric , Munden  Gina , Hussain M. Shazam , Abdulrazzak Mohammad A , Uchino  Ken , Katzan  Irene , Lu  Mei , Toth  Gabor , Russman  Andrew , Wisco  Dolora , Sundararajan  Jayashree , Buletko  Andrew , Bain  Mark , Moore  Nina , Witek  Alex , Cierny  Marek , Mahapatra  Ashutosh , Kharal  Ghulum , Limbert  Denice , Resser  Tina , Sweeney  Laura J , Chen Michael , Munich  Stephan , Crowley  Richard , McLaughlin  Elizabeth , Song  Sarah , McWilliams  Rebecca , Jacher  Bartosz , Warach Steven , Milling  Truman J. , Miley  Jefferson , Ellington  Kent , Regan  Aliaksandra , Erfan  Jessica , Mawla  Manzure , Davis  Lisa , Zuck  Nathan , Budzik Ron F , Hicks William J , Vora  Nirav , Pema  Peter , Alhajeri  Abdulnasser , Loochtan  Aaron , Rai  Vivek , Katz  Brian , Koss  Adam , Dedhia Nikita , Groezinger  Katy , Heckathorn  Megan , Bartelt Heather , Sangha Navdeep , Le Duy , Feng Lei  , Chao Kuo , Cheng  Pamela K , Ajani  Zahra A , Lui  Catherine L , Sharma  Ashima , Kozak Osman , Mackenzie Larami , Choe Hana , Bussinger  Patricia , DePalmo  Ashley , Hassan Ameer E , Tekle Wondwossen , Georgiadis Alexandros , Sanchez  Olive , Smith  Pualani , Gibson Daniel , Wallace Adam , Mente Tracy , Wilson Margaret , Ortega-Gutierrez Santiago , Samaniego Edgar , Derdeyn  Colin , Dlouhy  Kathleen , Hasan  David , Hayakawa  Minako , Leira  Enrique , Limaye  Kaustubh , Shaban  Amir , Shim  Hyung Sub , Ghannam  Malik , Zeballos Cynthia , Maljaars Jason , Koul Prateeka , Almajali Mohammad , Olalde  Heena , Kekinagath Harika A , Elijovich Lucas , Arthur  Adam , Hoit  Daniel , Nickele  Christopher , Inoa  Violiza , Goyal  Nitin , Wilson  Stephanie , Parsha  Kaushik , Nolte  Amanda , Herial Nabeel , Jabbour Pascal , Tjoumakaris  Stavropoula , Gooch  Michael Reid , Theofanis   Thana , Rosenwasser  Robert H. , Schunemann Victoria , Tahir Rizwan , Eldin  Mohamed S , Jabre  Roland , Chen  Jared , Jones  Nadirah , Kasner Scott , Cucchiara  Brett L , Messe  Steven Russell , Witsch  Jens , George  Donna , Favilla  Christopher , Yuan  Qingyang , Stein  Laura A , Novello  Paul , Rothstein  Aaron , Cristancho  Daniel , Sloane  Kelly , Humbert  Kelley , Zuflacht  Jonah , Kumar  Arooshi , Khan  Farhan , Mullen  Michael , Dawod  Judy , Burkhardt  Jan-Karl , Jankowitz  Brian , Pukenas  Bryan , Choudhri  Omar , Ramchand  Preethi , Reyes-Esteves  Sahily , Kone  Gbambele , Kvantaliani  Nino , Rosso  Michela , Cole  Sydni , Khazaal  Ossama , Gallatti  Nichole , Tsai Jenny , Min  Jiangyong , Wees  Nabil , Abdallah  Amjad , Khan  Muhib A. , Khan  Nadeem , Ahrar Asad , Mazaris Paul , Malgorzata Miller , Singer Justin , Groseclose Ryan S. , Sultan  Beenish I. , Sahlein Daniel , Amuluru  Krishna , Scott  John , DeNardo  Andrew , Rosenbaum  David , Campbell  Kati , Gandhi Chirag , Al-Mufti  Fawaz , Kaur  Gurmeen , Santarelli Justin , Lemrick  Nicole , Cero  Heather , Clare  Kevin , Nolan  Bridget , Schaafsma Joanna , Stewart Tim , Cayley Anne , Jaigobin Cheryl , Casaubon Leanne , Nicholson Patrick , Agid Ronit , Silver Frank , Pikula Aleksandra , To William , Crellin Lisa , Shuaib Ashfaq , Sobreira Nina , Campbell Bruce C , Yan Bernard , Yogendrakumar Vignan , Ng Felix C , Mitchell Peter J , Dowling Richard J , Bush Steven J , Williams Cameron , Yassi Nawaf , Pavlin-Premrl Davor , Beharry James , Balabanski Anna , Santos Angela Dos , Sharobeam Angelos , Valente Michael , Park Ashley , Wong Joseph , McDonald Amy , Jackson David , Sharma Gagan , Guha Prodipta , Rokaha Birendra , Kleinig Timothy J , Scroop Rebecca , Kurunawai Craig , Mahadevan Joshua , Goh Rudy , Drew Roy , Cordato Dennis , Manning Nathan , Parsons Mark , McQuinn Alex , Wenderoth Jason , Cheung Andrew , McDougall Alan , Thomas James , Cappelen-Smith Cecilia , Blair Christopher , Edwards Leon , Whitely Justin , Helou Jacob , Miller Megan , Wu Teddy Y , Collecutt Wayne , Colgan Frances , Krauss Martin , Laing Andrew , Wilson Duncan , Fink John , LeHeron Campbell , Mason Deborah , Green  Rosemary , Bremner Kathleen , Ribo Marc , Tomasello Alejandro , Ruiz Manuel Requena , Gadea Marta Olive , Sanjuan Estela , Cendrero Judith , Blasco Jordi , Renu Arturo , Roman Luis San , Urra Xabier , Santana Daniel , Cabrera Jose Maria , Llull Laura , López-Rueda Antonio , Cabero Andrea , Serrano Elena , Ossa Natalia Perez de la , Hernández-Pérez Maria , Millán Mònica , Gomis Meritxell , Bustamante Alejandro , Dorado Laura , Gómez-Choco Manuel , Remollo Sebastià , Castaño Carlos , Werner Mariano , Muñoz-Narbona Lucia , Cardona Pere , Quesada Helena , Lara Blanca , Paipa Andres , Nuñez Anna , Cuba Victor , Chirife Oscar , Aja Lucia , Miquel Maria Angeles de , Arenillas Juan F , Alfonso Mercedes De Lera , Araque María Esther Ramos , Calleja Ana I , Cortijo Elisa , Martínez-Galdámez Mario , Schüller Miguel , Galván Jorge , Muñoz Javier Reyes , Vicente Beatriz Gómez , Psychogios Marios , Brehm Alex 
Published: February 2024

ImportanceWhether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain.ObjectiveTo 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 ParticipantsAn 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.InterventionEVT vs MM.Main Outcomes and MeasuresPrimary outcome was functional outcome—90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values &amp;gt;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.ResultsAmong 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 RelevanceIn 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 RegistrationClinicalTrials.gov Identifier: NCT03876457