title: Effect of alteplase within 6 hours of acute ischemic stroke on all-cause mortality (third International Stroke Trial).
abstract: OBJECTIVE
  Prompt thrombolytic therapy with intravenous alteplase reduces disability after acute ischemic stroke. In an exploratory analysis, we examined whether long-term survival varied by baseline characteristics after alteplase.
  
  
  METHODS
  In this open-treatment, international, randomized, controlled trial, ischemic stroke patients were randomly allocated <6 hours of onset to intravenous alteplase (0.9 mg/kg) plus standard care (n=1515) or standard care alone (n=1520). We followed patients to death, censoring when last known to be alive. We grouped patients by delay to randomization, and good or poor predicted prognosis (calculated from baseline National Institutes of Health Stroke Scale [NIHSS] score and age). We present absolute mortality differences between treated and control groups at 7 days, 6 months, and 18 months poststroke.
  
  
  RESULTS
  Alteplase was not associated with a significant increase in mortality within 18 months (0.6% [95% confidence interval (CI), -2.9% to +4.2] P=0.72] in all patients with complete vital status (99.9%, 3034/3035). In patients randomized <3 hours of stroke, 18-month mortality was lower in the alteplase-treated group than the control group (40.6% [95% CI, 42.6-52.7] versus 47.8% [95% CI, 35.5-45.3]; P=0.0434]. The difference in 18-month mortality between alteplase-treated and control patients was greater in patients who were randomized early (<3 hours) compared with late (3-6 hours; +9% [95% CI, 1-17]; P=0.0317). Alteplase led to a greater improvement in 18-month survival in patients with a poor prognosis than in patients with a good prognosis (+8% [95% CI, 2-14]; P=0.0091).
  
  
  CONCLUSIONS
  These exploratory analyses of the third International Stroke Trial (IST-3) trial support improving acute stroke patients' access to earlier alteplase treatment, treatment of patients with poor prognosis, and further randomized controlled trials in minor stroke to replicate these findings.
  
  
  BACKGROUND
  http://www.controlled-trials.com. Unique identifier: ISRCTN25765518.
authors.affiliation: From the Centre for Clinical Brain Sciences (W.N.W., G.C., J.W., P.S.) and Centre for Population Health Sciences (D.T., G.M.), University of Edinburgh, United Kingdom; Neurological & Mental Health Division, George Institute for Global Health, University of Sydney, Australia (R.I.L.); and Neuroimaging Sciences, Edinburgh, United Kingdom (J.W.). william.whiteley@ed.ac.uk.
authors.forename: William N
authors.initials: WN
authors.lastname: Whiteley
authors.affiliation: From the Centre for Clinical Brain Sciences (W.N.W., G.C., J.W., P.S.) and Centre for Population Health Sciences (D.T., G.M.), University of Edinburgh, United Kingdom; Neurological & Mental Health Division, George Institute for Global Health, University of Sydney, Australia (R.I.L.); and Neuroimaging Sciences, Edinburgh, United Kingdom (J.W.).
authors.forename: Douglas
authors.initials: D
authors.lastname: Thompson
authors.affiliation: From the Centre for Clinical Brain Sciences (W.N.W., G.C., J.W., P.S.) and Centre for Population Health Sciences (D.T., G.M.), University of Edinburgh, United Kingdom; Neurological & Mental Health Division, George Institute for Global Health, University of Sydney, Australia (R.I.L.); and Neuroimaging Sciences, Edinburgh, United Kingdom (J.W.).
authors.forename: Gordon
authors.initials: G
authors.lastname: Murray
authors.affiliation: From the Centre for Clinical Brain Sciences (W.N.W., G.C., J.W., P.S.) and Centre for Population Health Sciences (D.T., G.M.), University of Edinburgh, United Kingdom; Neurological & Mental Health Division, George Institute for Global Health, University of Sydney, Australia (R.I.L.); and Neuroimaging Sciences, Edinburgh, United Kingdom (J.W.).
authors.forename: Geoff
authors.initials: G
authors.lastname: Cohen
authors.affiliation: From the Centre for Clinical Brain Sciences (W.N.W., G.C., J.W., P.S.) and Centre for Population Health Sciences (D.T., G.M.), University of Edinburgh, United Kingdom; Neurological & Mental Health Division, George Institute for Global Health, University of Sydney, Australia (R.I.L.); and Neuroimaging Sciences, Edinburgh, United Kingdom (J.W.).
authors.forename: Richard I
authors.initials: RI
authors.lastname: Lindley
authors.affiliation: From the Centre for Clinical Brain Sciences (W.N.W., G.C., J.W., P.S.) and Centre for Population Health Sciences (D.T., G.M.), University of Edinburgh, United Kingdom; Neurological & Mental Health Division, George Institute for Global Health, University of Sydney, Australia (R.I.L.); and Neuroimaging Sciences, Edinburgh, United Kingdom (J.W.).
authors.forename: Joanna
authors.initials: J
authors.lastname: Wardlaw
authors.affiliation: From the Centre for Clinical Brain Sciences (W.N.W., G.C., J.W., P.S.) and Centre for Population Health Sciences (D.T., G.M.), University of Edinburgh, United Kingdom; Neurological & Mental Health Division, George Institute for Global Health, University of Sydney, Australia (R.I.L.); and Neuroimaging Sciences, Edinburgh, United Kingdom (J.W.).
authors.forename: Peter
authors.initials: P
authors.lastname: Sandercock
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: mortality; randomized controlled trial; thrombolytic therapy