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Thrombolytic therapy with intravenous alteplase within 4.5 hours of ischemic stroke onset increases the overall likelihood of an excellent outcome (no, or nondisabling, symptoms). Any improvement in functional outcome distribution has value, and herein we provide an assessment of the effect of alteplase on the distribution of the functional level by treatment delay, age, and stroke severity.Prespecified pooled analysis of 6756 patients from 9 randomized trials comparing alteplase versus placebo/open control. Ordinal logistic regression models assessed treatment differences after adjustment for treatment delay, age, stroke severity, and relevant interaction term(s).Treatment with alteplase was beneficial for a delay in treatment extending to 4.5 hours after stroke onset, with a greater benefit with earlier treatment. Neither age nor stroke severity significantly influenced the slope of the relationship between benefit and time to treatment initiation. For the observed case mix of patients treated within 4.5 hours of stroke onset (mean 3 hours and 20 minutes), the net absolute benefit from alteplase (ie, the difference between those who would do better if given alteplase and those who would do worse) was 55 patients per 1000 treated (95% confidence interval, 13-91; P=0.004).Treatment with intravenous alteplase initiated within 4.5 hours of stroke onset increases the chance of achieving an improved level of function for all patients across the age spectrum, including the over 80s and across all severities of stroke studied (top versus bottom fifth means: 22 versus 4); the earlier that treatment is initiated, the greater the benefit.


Journal article




American Heart Association

Publication Date





2373 - 2379


From the Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (K.R.L.); Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, United Kingdom (J.E., L.B., C.B.); Statistics Department, Boehringer Ingelheim, Germany (E.B.); Melbourne Brain Centre, The Royal Melbourne Hospital and University of Melbourne, Australia (S.M.D.); Stroke Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia (G.A.D.); Mobile Stroke Unit and Stroke Research Program, Memorial Hermann Hospital, Houston, TX (J.C.G.); Department of Neurology, Helsinki University Hospital and Clinical Neurosciences, University of Helsinki, Finland (M.K.); Department of Neuroradiology, Technische Universität, Dresden, Germany (R.v.K.); Stanford Stroke Center, Palo Alto, CA (M.G.L.); Discipline of Medicine, Westmead Hospital Clinical School, George Institute for Global Health, University of Sydney, NSW, Australia (R.I.L.); Department of Neurology, Cedars-Sinai, Los Angeles, CA (P.L.); Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, United Kingdom (G.D.M.); Centre for Clinical Brain Sciences, University of Edinburgh, United Kingdom (P.A.G.S., J.M.W., W.N.W.); Department of Neurology and Psychiatry, Sapienza University of Rome, Italy (D.T.); Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan (K.T.); Department of Neurology, University of Heidelberg, Im Neuenheimer Feld, Germany (W.H.); and Department of Biostatistics, UAB School of Public Health, Birmingham, AL (G.H.).


Stroke Thrombolysis Trialists’ Collaborators Group