Extending thrombolysis to 4·5–9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data

作者：Bruce Campbell, Henry Ma, Peter A. Ringleb, Mark Parsons, Leonid Churilov, Martin Bendszus, Christopher Levi, Chung Hsu, Timothy Kleinig, Marc Fatar, Didier Leys, Carlos A. Molina, Tissa Wijeratne, Sami Curtze, Helen M. Dewey, P. Alan Barber, Kenneth Butcher, Deidre Anne De Silva, Christopher F. Bladin, Nawaf Yassi, Johannes Pfaff, Gagan Sharma, Andrew Bivard, Patricia Desmond, Stefan Schwab, Peter D. Schellinger, Bernard Yan, Peter Mitchell, Joaquı́n Serena, Danilo Toni, Vincent Thijs, Werner Hacke, Stephen M. Davis, Geoffrey A. Donnan, Geoffrey A. Donnan, Stephen M. Davis, Henry Ma, Bruce Campbell, Leonid Churilov, Mark Parsons, Bernard Yan, Peter Mitchell, Nawaf Yassi, Gagan Sharma, Patricia Desmond, Thomas J. Oxley, Teddy Y. Wu, Darshan Shah, Henry Zhao, Edrich Rodrigues, Patrick Salvaris, Fana Alemseged, Felix Ng, Cameron Williams, Jo-Lyn Ng, Hans T.H. Tu, Amy McDonald, David M. Jackson, Jessica Tsoleridis, Rachael McCoy, Lauren Pesavento, Louise Weir, Andrew Bivard, Timothy Kleinig, Sanjay R. Patel, Jackson Harvey, Jeyaledchumy Mahadevan, EunSun Cheong, Anna Balabanski, Michael F. Waters, Roy Drew, Jennifer Cranefield, Tissa Wijeratne, Elizabeth A. Mackey, Sherisse Celestino, Essie Low, Helen M. Dewey, Christopher F. Bladin, Poh Sien Loh, Philip Choi, Skye Coote, Tanya Frost, Kyla B. Hogan, Cheng Ding, S. McModie, W.W. Zhang, Christopher Kyndt, Alan Moore, Zofia Ross, Jack Edward Liu, Ferdinand Miteff, Christopher Levi, Timothy Ang, Neil J. Spratt, Carlos García-Esperón, Lara Kaauwai, Thanh G. Phan, John Ly, Shaloo Singhal, Benjamin Clissold, Kitty Wong, Martín Krause, Susan Day, Jonathan Sturm, Bill O'Brian, Rohan Grimley, Vincent Thijs, Marion Simpson, Matthew Lee-Archer, Amy Brodtmann, Bronwyn Coulton, Dennis Young, Andrew Wong, Claire Muller, Deborah Field, Wilson Vallat, Vanessa Maxwell, Peter Bailey, Arman Sabet, Sachin Mishra, Meng H. Tan, Kola George, P. Alan Barber, Lin‐Bo Zhao, Atte Meretoja, Sami Curtze, Turgut Tatlisumak, Gerli Sibolt, Marjaana Tiainen, Matti Koivu, Karolinaa Aarnio, Jyri J. Virta, O. Kasari, S. Eirola, Mu-Chien Sun, T.C. Chen, Chia‐Hui Chuang, Y.Y. Chen, C.M. Lin, S Ho, Pi-Ju Hsiao, Cho-Jen Tsai, Wenguo Huang, Dongyuan Yang, H.-Y. Huang, W.C. Wang, Cindy Liu, Mengxin Lu, Cheng‐Hsien Lu, W.L. Kung, Shou-Feng Jiang, Yun‐Cheng Wu, Shiyu Huang, Chun Tseng, Liang‐Wei Tseng, Yongchun Guo, Ding-lai Lin, Chao-Wen Hsu, C.W. Kuan, Jia‐Shuo Hsu, Hsin‐Chi Tsai, Motofumi Suzuki, Yameng Sun, HongJie Chen, Chi‐Ju Lu, Chun-Jen Lin, C.C. Huang, H. J. Chu, C.Y. Lee, Warren Chang, Yu‐Chun Lo, Yueh‐Han Hsu, Chung‐Hwan Chen, Pi‐Shan Sung, C.L. Ysai, Jiann‐Shing Jeng, Sung‐Chun Tang, Li‐Kai Tsai, Shin‐Joe Yeh, Y.C. Lee, Y.T. Wang, T.C. Chung, Chaur‐Jong Hu, Lok Yiu Chan, Yu‐Wei Chiou, Li-Ming Lien, Hsu-Ling Yeh, Jen-Hao Yeh, W.H. Chen, Chee Lan Lau, Anna Marie Chang, I.Y. Lee, M.Y. Huang, J.T. Lee, G.S. Peng, Jeremy C. Lim, Yi‐Cheng Hsu, Chao Lin, C.A. Cheng, Chia‐Hung Yen, Fang Yang, Chiun Hsu, Yueh‐Feng Sung, Chia‐Kuang Tsai, Chia-Lung Tsai, Pi-Ju Hsiao, A. Lee, Graeme J. Hankey, David Blacker, Richard Gerraty, Chun‐I Chen, C-S. Hsu, Elise S. Cowley, Rachael McCoy, Michele Sallaberger, Barry Snow, John Kolbe, R. Stark, John T. King, Richard Macdonnell, John Attia, Catherine D’Este, Julie Bernhardt, Leeanne M. Carey, Dominique A. Cadilhac, Craig S. Anderson, David W. Howells, P. Alan Barber, Alan Connelly, Malcolm Macleod, Victoria O’Collins, W.J. Wilson, Lisa Macaulay, Martin Bendszus, Erich Bluhmki, Christoph Eschenfelder, Werner Hacke, Carlos A. Molina, Didier Leys, Peter A. Ringleb, Peter D. Schellinger, Stefan Schwab, Danilo Toni, Nils Wahlgren, Joanna M. Wardlaw, Catherine Oppenheim, Kennedy R. Lees, Markku Kaste, Rüdiger von Kummer, Gilles Châtellier, Rico Laage, Xavier Nuñez, Christina Ehrenkrona, Ann-Sofie Svenson, Lynda Cove, Kurt Niederkorn, Franz Gruber, Peter Kapeller, Robert Mikulík, Jean‐Louis Mas, Jörg Berrouschot, Jan Sobesky, Martin Köhrmann, Thorsten Steiner, Christof Kessler, Marc Fatar, Rainer Dziewas, Sven Poli, Katharina Althaus-Knaurer, Paolo Bovi, Alain Luna Rodríguez, Juan F. Arenillas, Keith W. Muir, Roland Veltkamp, Anand Dixit, Girish Muddegowda, Lalit Kala, Deidre Anne De Silva, Kenneth Butcher, Graham Byrnes, André Peeters, Jonathan B. Chalk, John Fink, Thomas Kimber, David Schultz, Peter J. Hand, Judith Frayne, Brian M. Tress, John J. McNeil, Rachel J. Burns, Claiborne Johnston, M.L. Williams · 发表于：The Lancet · 年份：2019 · DOI：10.1016/s0140-6736(19)31053-0 · 被引用次数：533 · 研究领域：Acute Ischemic Stroke Management、Stroke Rehabilitation and Recovery、Advanced MRI Techniques and Applications

BACKGROUND: Stroke thrombolysis with alteplase is currently recommended 0-4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis. METHODS: In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FINDINGS: We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%...