Assessing reperfusion and recanalization as markers of clinical outcomes after intravenous thrombolysis in the echoplanar imaging thrombolytic evaluation trial (EPITHET).

Author(s): De Silva DA, Fink JN, Christensen S, Ebinger M, Bladin C, Levi CR, Parsons M, Butcher K, Barber PA, Donnan GA, Davis SM, Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) Investigators

Affiliation(s): Division of Neurosciences, Royal Melbourne Hospital, Grattan Street, Parkville 3050, Victoria, Australia.

Publication date & source: 2009-08, Stroke., 40(8):2872-4. Epub 2009 May 28.

Publication type: Clinical Trial, Phase II; Comparative Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

BACKGROUND AND PURPOSE: Reperfusion and recanalization have both been used as surrogate markers of clinical outcome in trials of stroke thrombolysis. We aimed to prove that the beneficial impact of recanalization with intravenous tissue plasminogen activator on clinical outcomes is attributable to reperfusion in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). METHODS: EPITHET was a prospective, randomized, placebo-controlled trial of intravenous tissue plasminogen activator in the 3- to 6-hour window. Reperfusion was defined as >90% reduction in magnetic resonance perfusion-weighted imaging lesion volume and recanalization as improvement of MR angiographic Thrombolysis In Myocardial Infarction grading by > or =2 points from baseline to Day 3 to 5. RESULTS: At Day 3 to 5, reperfusion and recanalization with intravenous tissue plasminogen activator were strongly correlated. Reperfusion was associated with improved clinical outcome independent of whether recanalization occurred. In contrast, recanalization was not associated with clinical outcome when reperfusion was included as a covariate in regression analyses. CONCLUSIONS: Reperfusion is a surrogate marker of clinical outcomes independent of recanalization based on the criteria applied in EPITHET. The impact of recanalization on clinical outcomes was attributable to reperfusion.