Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/20844
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 N;Hacke, Werner;Davis, Stephen M;Donnan, Geoffrey A
Affiliation: Department of Radiology, University of Melbourne, Melbourne, VIC, Australia
Department of Neurology, Sapienza University of Roma, Rome, Italy
Department of Neuroradiology, Ruprecht Karls University Heidelberg, Heidelberg, Germany
Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
Department of Neurology, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany
Department of Neurology, Hospital CHU Lille, Lille, France
Department of Neurology, Hospital Vall d'Hebron, University of Barcelona, Barcelona, Spain
Department of Neurology, Helsinki University Hospital, Helsinki, Finland
Department of Neurology, Auckland City Hospital, University of Auckland, Auckland, New Zealand
Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore
Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany
Department of Neurology and Neurogeriatry, Johannes Wesling Medical Centre Minden, University Hospital of Ruhr-University Bochum, Bochum, Germany
Department of Neurology, Girona University Hospital, Biomedical Research Institute of Girona, Girona, Spain
Department of Medicine and Neurology, Melbourne Brain Centre, University of Melbourne, Melbourne, VIC, Australia
Division of Neurology, University of Alberta, Edmonton, AB, Canada
Department of Neurology, Ruprecht Karls University Heidelberg, Heidelberg, Germany
Royal Melbourne Hospital, and Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia
Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia
Department of Neurology, University of Melbourne, Melbourne, VIC, Australia
Department of Neurosciences, Eastern Health and Eastern Health Clinical School, Monash University, Melbourne, VIC, Australia
Western Hospital, Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia
Department of Neurology, Western Health, Sunshine Hospital, Melbourne, VIC, Australia
Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
Department of Medicine, School of Clinical Science, Monash University, Melbourne, VIC, Australia
Department of Neurology, Priority Research Centre for Brain and Mental Health Research, John Hunter Hospital, University of Newcastle, Newcastle, NSW, Australia
Department of Neurology, Royal Adelaide Hospital, Adelaide, SA, Australia
Issue Date: 21-May-2019
EDate: 2019-05-21
Citation: Lancet (London, England) 2019; online first: 21 May
Abstract: 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. 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. 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 alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23-76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81-2·96, p=0·66). Patients with ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis. None.
URI: http://ahro.austin.org.au/austinjspui/handle/1/20844
DOI: 10.1016/S0140-6736(19)31053-0
ORCID: Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
0000-0002-6614-8417
PubMed URL: 31128925
Type: Journal Article
Appears in Collections:Journal articles

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