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

Title: Extending thrombolysis to 4·5–9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data
Authors: Campbell, Bruce C V; Ma, Henry; Ringleb, Peter A; Parsons, Mark W; Churilov, Leonid; Bendszus, Martin; Levi, Christopher R; Hsu, Chung; Kleinig, Timothy J; Fatar, Marc; Leys, Didier; Molina, Carlos; Wijeratne, Tissa; Curtze, Sami; Dewey, Helen M; Barber, P Alan; Butcher, Kenneth S; De Silva, Deidre A; Bladin, Christopher F; Yassi, Nawaf; Pfaff, Johannes A R; Sharma, Gagan; Bivard, Andrew; Desmond, Patricia M; Schwab, Stefan; Schellinger, Peter D; Yan, Bernard; Mitchell, Peter J; Serena, Joaquín; Toni, Danilo; Thijs, Vincent; Hacke, Werner; Davis, Stephen M; Donnan, Geoffrey A; Davis, Stephen M.; Campbell, Bruce C.V.; Parsons, Mark W.; Mitchell, Peter J.; Desmond, Patricia M.; Oxley, Thomas; Wu, Teddy Y.; Shah, Darshan; Zhao, Henry; Rodrigues, Edrich; Salvaris, Patrick; Alemseged, Fana; Ng, Felix; Williams, Cameron; Ng, Jo-Lyn; Tu, Hans T-H.; McDonald, Amy; Jackson, David; Tsoleridis, Jessica; McCoy, Rachael; Pesavento, Lauren; Weir, Louise; Kleinig, Timothy J.; Patel, S.; Harvey, J.; Mahadevan, J.; Cheong, E.; Balabanski, Anna; Waters, Michael; Drew, Roy; Cranefield, Jennifer; Mackey, Elizabeth; Celestino, Sherisse; Low, Essie; Dewey, Helen M.; Bladin, Christopher F.; Loh, Poh Sien; Choi, Philip M.; Coote, Skye; Frost, Tanya; Hogan, K.; Ding, C.; McModie, S.; Zhang, W.W.; Kyndt, Christopher; Moore, A.; Ross, Z.; Liu, J.; Miteff, Ferdinand; Levi, Christopher R.; Ang, Timothy; Spratt, Neil; Garcia-Esperon, Carlos; Kaauwai, Lara; Phan, Thanh G.; Ly, John; Singhal, Shaloo; Clissold, Benjamin; Wong, Kitty; Krause, Martin; Day, Susan; Sturm, Jonathan; O'Brian, Bill; Grimley, Rohan; Simpson, Marion; Lee-Archer, Matthew; Brodtmann, Amy; Coulton, Bronwyn; Young, Dennis; Wong, Andrew A.; Muller, Claire; Field, Deborah K.; Vallat, W.; Maxwell, Vanessa; Bailey, Peter; Sabet, Arman; Mishra, Sachin; Tan, Meng; George, K.; Barber, P. Alan; Zhao, L.; Meretoja, Atte; Tatlisumak, Turgut; Sibolt, G.; Tiainen, M.; Koivu, M.; Aarnio, K.; Virta, J.; Kasari, O.; Eirola, S.; Sun, M.C.; Chen, T.C.; Chuang, C.S.; Chen, Y.Y.; Lin, C.M.; Ho, S.C.; Hsiao, P.M.; Tsai, C.H.; Huang, W.S.; Yang, Y.W.; Huang, H.Y.; Wang, W.C.; Liu, C.H.; Lu, M.K.; Lu, C.H.; Kung, W.L.; Jiang, S.K.; Wu, Y.H.; Huang, S.C.; Tseng, C.H.; Tseng, L.T.; Guo, Y.C.; Lin, D.; Hsu, C.T.; Kuan, C.W.; Hsu, J.P.; Tsai, H.T.; Suzuki, M.; Sun, Y.; Chen, H.F.; Lu, C.J.; Lin, C.H.; Huang, C.C.; Chu, H.J.; Lee, C.Y.; Chang, W.H.; Lo, Y.C.; Hsu, Y.T.; Chen, C.H.; Sung, P.S.; Ysai, C.L.; Jeng, J.S.; Tang, S.C.; Tsai, L.K.; Yeh, S.J.; Lee, Y.C.; Wang, Y.T.; Chung, T.C.; Hu, C.J.; Chan, L.; Chiou, Y.W.; Lien, L.M.; Yeh, H.L.; Yeh, J.H.; Chen, W.H.; Lau, C.L.; Chang, A.; Lee, I.Y.; Huang, M.Y.; Lee, J.T.; Peng, G.S.; Lim, J.C.; Hsu, Y.D.; Lin, C.C.; Cheng, C.A.; Yen, C.H.; Yang, F.C.; Hsu, C.H.; Sung, Y.F.; Tsai, C.K.; Tsai, C.L.; Lee, A.; Hankey, Graeme; Blacker, David; Gerraty, Richard; Chen, C-I.; Hsu, C-S.; Cowley, Elise; Sallaberger, Michele; Snow, Barry; Kolbe, John; Stark, Richard; King, John; Macdonnell, Richard; Attia, John; D'Este, Catherine; Bernhardt, Julie; Carey, Leeanne; Cadilhac, Dominique; Anderson, Craig; Howells, David; Barber, A.; Connelly, Alan; Macleod, Malcolm; O'Collins, Victoria; Wilson, W.; Macaulay, L.; Bluhmki, Erich; Eschenfelder, Christoph; Ringleb, Peter; Schellinger, Peter; Wahlgren, Nils; Wardlaw, Joanna; Oppenheim, Catherine; Lees, Kennedy R.; Kaste, Markku; von Kummer, Rüdiger; Chatellier, Gilles; Laage, Rico; Nuñez, Xavier; Ehrenkrona, Christina; Svenson, Ann-Sofie; Cove, Lynda; Niederkorn, Kurt; Gruber, Franz; Kapeller, Peter; Mikulik, Robert; Mas, Jean-Louis; Berrouschot, Jörg; Sobesky, Jan; Köhrmann, Martin; Steiner, Thorsten; Kessler, Christof; Dziewas, Rainer; Poli, Sven; Althaus-Knaurer, Katharina; Bovi, Paolo; Rodriguez, Alain L.; Arenillas, Juan F.; EXTEND, ECASS-4, and EPITHET Investigators; Veltkamp, Roland; Dixit, Anand; Muddegowda, Girish; Kala, Lalit; De Silva, Deidre A.; Butcher, Kenneth S.; Byrnes, G.; Peeters, Andre; Chalk, J.B.; Fink, John N.; Kimber, Thomas E.; Schultz, David; Hand, Peter J.; Frayne, Judith; Tress, Brian M.; McNeil, John; Burns, R.; Johnston, C.; Williams, M.
Publisher Information: The Lancet Publishing Group
Publication Year: 2019
Collection: University of Glasgow: Enlighten - Publications
Description: 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%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15–2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the ...
Document Type: article in journal/newspaper
Language: unknown
Relation: Campbell, B. C. V. et al. (2019) Extending thrombolysis to 4·5–9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data. Lancet , 394(10193), pp. 139-147. (doi:10.1016/S0140-6736(19)31053-0 ) (PMID:31128925)
Availability: https://eprints.gla.ac.uk/210334/
Accession Number: edsbas.91923AE2
Database: BASE