title: Reperfusion after 4.5 hours reduces infarct growth and improves clinical outcomes.
abstract: BACKGROUND
  The currently proven time window for thrombolysis in ischemic stroke is 4.5 h. Beyond this, the risks and benefits of thrombolysis are uncertain.
  
  
  OBJECTIVE
  To determine whether thrombolysis and reperfusion were beneficial after 4.5 h, we examined clinical and radiological outcomes in patients treated with tissue plasminogen activator or placebo within 4.5-6 h, using data from the Echoplanar Imaging Thrombolytic Evaluation Trial.
  
  
  METHODS
  In the Echoplanar Imaging Thrombolytic Evaluation Trial, ischemic stroke patients presenting three to six-hours after stroke onset were randomized to tissue plasminogen activator or placebo, without knowledge of magnetic resonance imaging results. This analysis was restricted to patients treated between 4.5 and 6 h. The effect of tissue plasminogen activator and reperfusion on infarct growth between baseline diffusion-weighted imaging and day 90 T2 imaging was assessed, along with good neurological outcome (≥8 point reduction or reaching 0-1 at 90 days on National Institutes of Health Stroke Scale) and functional outcome (modified Rankin scale). The effect of tissue plasminogen activator on reperfusion was also analyzed.
  
  
  RESULTS
  Sixty-nine patients were treated 4.5-6 h after onset, and infarct growth was assessed in 63. Tissue plasminogen activator was associated with lower relative growth (94% vs. 168%, P = 0.03) and a trend to lower absolute growth (-0.17 ml versus 9.6 ml, P = 0.07). Reperfusion was increased in the tissue plasminogen activator group (58% versus 25%, P = 0.03) and was associated with increased rates of good neurological (86% versus 28% P < 0.001) and functional (modified Rankin scale 0-2 73% versus 34%, P = 0.01) outcomes. Reperfusion was strongly associated with lower relative (80% versus 189%, P < 0.001) and absolute (-2.5 ml versus 40 ml, P < 0.001) infarct growth.
  
  
  CONCLUSIONS
  Thrombolysis 4.5-6 h after stroke onset reduced infarct growth and increased the rate of reperfusion, which was associated with good neurological and functional outcome.
authors.affiliation: Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia.
authors.forename: Miguel R
authors.initials: MR
authors.lastname: Picanço
authors.forename: Søren
authors.initials: S
authors.lastname: Christensen
authors.forename: Bruce C V
authors.initials: BC
authors.lastname: Campbell
authors.forename: Leonid
authors.initials: L
authors.lastname: Churilov
authors.forename: Mark W
authors.initials: MW
authors.lastname: Parsons
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Desmond
authors.forename: P Alan
authors.initials: PA
authors.lastname: Barber
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Levi
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Bladin
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Donnan
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Davis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015424:Reperfusion / Q000379:methods*; D012720:Severity of Illness Index; D020521:Stroke / Q000150:complications / Q000628:therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: MRI; stroke; tPA; thrombolysis