title: Thrombolytic therapy for acute ischemic stroke beyond three hours.
abstract: BACKGROUND
  Ischemic cerebrovascular accidents remain a leading cause of morbidity and mortality. Thrombolytic therapy for acute ischemic stroke within 3h of symptom onset of highly select patients has been advocated by some groups since 1995, but trials have yielded inconsistent outcomes. One recent trial demonstrated significant improvement when the therapeutic window was extended to 4.5h.
  
  
  OBJECTIVE
  Does the intravenous systemic administration of tPA within 4.5h to select patients with acute ischemic stroke improve functional outcomes?
  
  
  METHODS
  All randomized controlled trials enrolling patients within 4.5h were identified, in addition to a meta-analysis of these trial data.
  
  
  RESULTS
  The National Institute of Neurological Disorders and Stroke (NINDS) and European Cooperative Acute Stroke Study III (ECASS III) clinical trials demonstrated significantly improved outcomes at 3 months, with increased rates of intracranial hemorrhage, whereas ECASS II and the Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study showed increased hemorrhagic complications without improving outcomes. Meta-analysis of trial data from all ECASS trials, NINDS, and ATLANTIS suggest that thrombolysis within 4.5h improves functional outcomes.
  
  
  CONCLUSIONS
  Ischemic stroke tPA treatment within 4.5h seems to improve functional outcomes and increases symptomatic intracranial hemorrhage rates without significantly increasing mortality.
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Carpenter
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Keim
authors.forename: William Kenneth
authors.initials: WK
authors.lastname: Milne
authors.forename: William J
authors.initials: WJ
authors.lastname: Meurer
authors.forename: William G
authors.initials: WG
authors.lastname: Barsan
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000150:complications*; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D010959:Tissue Plasminogen Activator