title: The effects of alteplase 3 to 6 hours after stroke in the EPITHET-DEFUSE combined dataset: post hoc case-control study.
abstract: OBJECTIVE
  Two phase 2 studies of alteplase in acute ischemic stroke 3 to 6 hours after onset, Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; a randomized, controlled, double-blinded trial), and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study (DEFUSE; open-label, treatment only) using MR imaging-based outcomes have been conducted. We have pooled individual patient data from these to assess the response to alteplase. The primary hypothesis was that alteplase would significantly attenuate infarct growth compared with placebo in mismatch-selected patients using coregistration techniques.
  
  
  METHODS
  The EPITHET-DEFUSE study datasets were pooled while retaining the original inclusion and exclusion criteria. Significant hypoperfusion was defined as a Tmax delay >6 seconds), and coregistration techniques were used to define MR diffusion-weighted imaging/perfusion-weighted imaging mismatch. Neuroimaging, parameters including reperfusion, recanalization, symptomatic intracerebral hemorrhage, and clinical outcomes were assessed. Alteplase and placebo groups were compared for the primary outcome of infarct growth as well for secondary outcome measures.
  
  
  RESULTS
  From 165 patients with adequate MR scans in the EPITHET-DEFUSE pooled data, 121 patients (73.3%) were found to have mismatch. For the primary outcome analysis, 60 patients received alteplase and 41 placebo. Mismatch patients receiving alteplase had significantly attenuated infarct growth compared with placebo (P=0.025). The reperfusion rate was also increased (62.7% vs 31.7%; P=0.003). Mortality and clinical outcomes were not different between groups.
  
  
  CONCLUSIONS
  The data provide further evidence that alteplase significantly attenuates infarct growth and increases reperfusion compared with placebo in the 3- to 6- hour time window in patients selected based on MR penumbral imaging.
authors.affiliation: FRACP, Level 2 Alan Gilbert Bldg, 161 Barry St, Carlton S Victoria 3053, Australia.
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Ogata
authors.forename: Soren
authors.initials: S
authors.lastname: Christensen
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Nagakane
authors.forename: Henry
authors.initials: H
authors.lastname: Ma
authors.forename: Bruce C V
authors.initials: BC
authors.lastname: Campbell
authors.forename: Leonid
authors.initials: L
authors.lastname: Churilov
authors.forename: Maarten G
authors.initials: MG
authors.lastname: Lansberg
authors.forename: Matus
authors.initials: M
authors.lastname: Straka
authors.forename: Deidre A
authors.initials: DA
authors.lastname: De Silva
authors.forename: Michael
authors.initials: M
authors.lastname: Mlynash
authors.forename: Roland
authors.initials: R
authors.lastname: Bammer
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Olivot
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Desmond
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Albers
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Davis
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Donnan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016208:Databases, Factual; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020521:Stroke / Q000188:drug therapy* / Q000453:epidemiology*; D015912:Thrombolytic Therapy / Q000639:trends; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D010959:Tissue Plasminogen Activator