title: Efficacy and safety of tissue plasminogen activator 3 to 4.5 hours after acute ischemic stroke: a metaanalysis.
abstract: OBJECTIVE
  The Third European Cooperative Acute Stroke Study (ECASS-3) demonstrated a benefit of treatment with intravenous tissue plasminogen activator (tPA) for acute stroke in the 3- to 4.5-hour time-window. Prior studies, however, have failed to demonstrate a significant benefit of tPA for patients treated beyond 3 hours. The purpose of this study was to produce reliable and precise estimates of the treatment effect of tPA by pooling data from all relevant studies.
  
  
  METHODS
  A metaanalysis was undertaken to determine the efficacy of tPA in the 3- to 4.5-hour time-window. The effect of tPA on favorable outcome and mortality was assessed.
  
  
  RESULTS
  The metaanalysis included data from patients treated in the 3- to 4.5-hour time-window in ECASS-1 (n=234), ECASS-2 (n=265), ECASS-3 (n=821) and The Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) (n=302). tPA treatment was associated with an increased chance of favorable outcome (odds ratio 1.31; 95% CI: 1.10 to 1.56; P=0.002) and no significant difference in mortality (odds ratio 1.04; 95% CI: 0.75 to 1.43; P=0.83) compared to placebo treated patients.
  
  
  CONCLUSIONS
  Treatment with tPA in the 3- to 4.5-hour time-window is beneficial. It results in an increased rate of favorable outcome without adversely affecting mortality.
authors.affiliation: Stanford Stroke Center, Stanford University Medical Center, Palo Alto, CA 94304-9705, USA. lansberg@stanford.edu
authors.forename: Maarten G
authors.initials: MG
authors.lastname: Lansberg
authors.forename: Erich
authors.initials: E
authors.lastname: Bluhmki
authors.forename: Vincent N
authors.initials: VN
authors.lastname: Thijs
mesh_terms: D000368:Aged; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000379:methods; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator