title: Effect of Intravenous Recombinant Tissue-Type Plasminogen Activator in Patients With Mild Stroke in the Third International Stroke Trial-3: Post Hoc Analysis.
abstract: OBJECTIVE
  Randomized trial evidence on the risk/benefit ratio of thrombolysis for mild stroke is limited. We sought to determine the efficacy of intravenous recombinant tissue-type plasminogen activator (IV r-tPA) in a subset of patients with mild deficit in the third International Stroke Trial (IST-3).
  
  
  METHODS
  IST-3 compared IV r-tPA with control within 6 hours of onset in patients for whom IV r-tPA was considered promising but unproven. Analysis was restricted to subjects randomized within 3 hours of onset with a baseline National Institutes of Health Stroke Scale ≤5, pretreatment blood pressure <185/110, and no other r-tPA exclusion criteria. We compared r-tPA and control arms for primary (Oxfordshire Handicap Score [OHS] 0-2) and secondary (ordinal OHS and OHS 0-1) outcomes at 6 months.
  
  
  RESULTS
  Among 3035 IST-3 subjects, 612 (20.2%) had an National Institutes of Health Stroke Scale ≤5; of these 106 (17.6%) met the restricted criteria. Allocation to r-tPA was associated with an increase in OHS 0 to 2 (84% r-tPA versus 65% control; adjusted odds ratio, 3.31; 95% confidence interval, 1.24-8.79) and a favorable shift in OHS distribution (adjusted odds ratio, 2.38; 95% confidence interval, 1.17-4.85). There was no significant effect of r-tPA on OHS 0 to 1 (60% versus 51%; adjusted odds ratio, 1.92; 95% confidence interval, 0.83-4.43).
  
  
  CONCLUSIONS
  This post hoc analysis in a highly selected sample of IST-3 supports the rationale of A Study of the Efficacy and Safety of Activase (Alteplase) in Patients With Mild Stroke (PRISMS) trial-a randomized, phase IIIb study to evaluate IV r-tPA in mild ischemic stroke.
authors.affiliation: From the Department of Neurology and Rehabilitation Medicine, University of Cincinnati, OH (P.K., J.P.B.); Genentech, Inc, South San Francisco, CA (D.T.); Division of Clinical Neurosciences (G.C., P.S.), and Division of Neuroimaging Sciences (J.M.W.), University of Edinburgh, Edinburgh, Scotland; Neurological and Mental Health Division, The George Institute for Global Health, University of Sydney, Sydney, Australia (R.I.L.); and Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y.). pooja.khatri@uc.edu.
authors.forename: Pooja
authors.initials: P
authors.lastname: Khatri
authors.affiliation: From the Department of Neurology and Rehabilitation Medicine, University of Cincinnati, OH (P.K., J.P.B.); Genentech, Inc, South San Francisco, CA (D.T.); Division of Clinical Neurosciences (G.C., P.S.), and Division of Neuroimaging Sciences (J.M.W.), University of Edinburgh, Edinburgh, Scotland; Neurological and Mental Health Division, The George Institute for Global Health, University of Sydney, Sydney, Australia (R.I.L.); and Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y.).
authors.forename: Darren
authors.initials: D
authors.lastname: Tayama
authors.affiliation: From the Department of Neurology and Rehabilitation Medicine, University of Cincinnati, OH (P.K., J.P.B.); Genentech, Inc, South San Francisco, CA (D.T.); Division of Clinical Neurosciences (G.C., P.S.), and Division of Neuroimaging Sciences (J.M.W.), University of Edinburgh, Edinburgh, Scotland; Neurological and Mental Health Division, The George Institute for Global Health, University of Sydney, Sydney, Australia (R.I.L.); and Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y.).
authors.forename: Geoff
authors.initials: G
authors.lastname: Cohen
authors.affiliation: From the Department of Neurology and Rehabilitation Medicine, University of Cincinnati, OH (P.K., J.P.B.); Genentech, Inc, South San Francisco, CA (D.T.); Division of Clinical Neurosciences (G.C., P.S.), and Division of Neuroimaging Sciences (J.M.W.), University of Edinburgh, Edinburgh, Scotland; Neurological and Mental Health Division, The George Institute for Global Health, University of Sydney, Sydney, Australia (R.I.L.); and Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y.).
authors.forename: Richard I
authors.initials: RI
authors.lastname: Lindley
authors.affiliation: From the Department of Neurology and Rehabilitation Medicine, University of Cincinnati, OH (P.K., J.P.B.); Genentech, Inc, South San Francisco, CA (D.T.); Division of Clinical Neurosciences (G.C., P.S.), and Division of Neuroimaging Sciences (J.M.W.), University of Edinburgh, Edinburgh, Scotland; Neurological and Mental Health Division, The George Institute for Global Health, University of Sydney, Sydney, Australia (R.I.L.); and Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y.).
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wardlaw
authors.affiliation: From the Department of Neurology and Rehabilitation Medicine, University of Cincinnati, OH (P.K., J.P.B.); Genentech, Inc, South San Francisco, CA (D.T.); Division of Clinical Neurosciences (G.C., P.S.), and Division of Neuroimaging Sciences (J.M.W.), University of Edinburgh, Edinburgh, Scotland; Neurological and Mental Health Division, The George Institute for Global Health, University of Sydney, Sydney, Australia (R.I.L.); and Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y.).
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Yeatts
authors.affiliation: From the Department of Neurology and Rehabilitation Medicine, University of Cincinnati, OH (P.K., J.P.B.); Genentech, Inc, South San Francisco, CA (D.T.); Division of Clinical Neurosciences (G.C., P.S.), and Division of Neuroimaging Sciences (J.M.W.), University of Edinburgh, Edinburgh, Scotland; Neurological and Mental Health Division, The George Institute for Global Health, University of Sydney, Sydney, Australia (R.I.L.); and Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y.).
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Broderick
authors.affiliation: From the Department of Neurology and Rehabilitation Medicine, University of Cincinnati, OH (P.K., J.P.B.); Genentech, Inc, South San Francisco, CA (D.T.); Division of Clinical Neurosciences (G.C., P.S.), and Division of Neuroimaging Sciences (J.M.W.), University of Edinburgh, Edinburgh, Scotland; Neurological and Mental Health Division, The George Institute for Global Health, University of Sydney, Sydney, Australia (R.I.L.); and Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y.).
authors.forename: Peter
authors.initials: P
authors.lastname: Sandercock
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D038622:Internationality; D008297:Male; D020521:Stroke / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: clinical trials; stroke; thrombolytic therapy