학술논문
Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations: Individual-patient-data meta-analysis of randomized trials.
Document Type
Academic Journal
Author
Hacke W; 1 Department of Neurology, University of Heidelberg, Heidelberg, Germany.; Lyden P; 2 Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, USA.; Emberson J; 3 MRC Population Health Research Unit (PHRU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.; 4 Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Baigent C; 3 MRC Population Health Research Unit (PHRU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.; 4 Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Blackwell L; 3 MRC Population Health Research Unit (PHRU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.; 4 Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Albers G; 5 Stanford Stroke Center, Palo Alto, USA.; Bluhmki E; 6 Boehringer Ingelheim, Ingelheim, Germany.; Brott T; 7 Mayo Clinic, Jacksonville, USA.; Cohen G; 8 Division of Neuroimaging Sciences, University of Edinburgh, UK.; Davis SM; 9 The Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia.; Donnan GA; 10 Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.; Grotta JC; 11 Memorial Hermann Hospital, Houston, USA.; Howard G; 12 Department of Biostatistics, University of Alabama at Birmingham, Birmingham, USA.; Kaste M; 13 Clinical Neurosciences, University of Helsinki, Helsinki, Finland.; 14 Department of Neurology, Helsinki University Hospital, Helsinki, Finland.; Koga M; 15 National Cerebral and Cardiovascular Centre, Suita, Japan.; von Kummer R; 16 Institute of Neuroradiology, Technische Universität, Dresden, Germany.; Lansberg MG; 5 Stanford Stroke Center, Palo Alto, USA.; Lindley RI; 17 Westmead Hospital Clinical School and George Institute for Global Health, University of Sydney, Sydney, Australia.; Olivot JM; 18 Centre Hospitalier Universitaire de Toulouse, Toulouse, France.; 19 Toulouse Neuroimaging Center, Toulouse, France.; Parsons M; 20 Department of Neurology, Royal Melbourne Hospital and University of Melbourne, Australia.; Sandercock PA; 21 Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.; Toni D; 22 Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.; Toyoda K; 15 National Cerebral and Cardiovascular Centre, Suita, Japan.; Wahlgren N; 23 Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.; Wardlaw JM; 8 Division of Neuroimaging Sciences, University of Edinburgh, UK.; Whiteley WN; 8 Division of Neuroimaging Sciences, University of Edinburgh, UK.; Del Zoppo G; 24 Department of Medicine, Department of Neurology, University of Washington, Seattle, USA.; Lees KR; 25 Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK.
Source
Publisher: SAGE Publications Country of Publication: United States NLM ID: 101274068 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1747-4949 (Electronic) Linking ISSN: 17474930 NLM ISO Abbreviation: Int J Stroke Subsets: MEDLINE
Subject
Language
English
Abstract
Background The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0-1) at 3-6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results Alteplase increased the odds of modified Rankin score 0-1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21-1.68 and 1.43, 1.23-1.65, respectively), but not in those outside the age-revised label (1.06, 0.90-1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76-1.25 and 1.01, 0.86-1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99-1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19-2.01 and 1.37, 1.17-1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97-1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77-1.26 and 1.02, 0.87-1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98-1.41). Conclusions An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.