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

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 &amp;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. 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