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(Stroke. 2009;40:2872.)
© 2009 American Heart Association, Inc.

Research Letters

Assessing Reperfusion and Recanalization as Markers of Clinical Outcomes After Intravenous Thrombolysis in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET)

Deidre A. De Silva, MRCP; John N. Fink, FRACP; Soren Christensen, PhD; Martin Ebinger, PhD; Christopher Bladin, PhD; Christopher R. Levi, FRACP; Mark Parsons, PhD; Ken Butcher, PhD; P. Alan Barber, PhD; Geoffrey A. Donnan, MD; Stephen M. Davis, MD for the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) Investigators

From the Royal Melbourne Hospital (D.A.D.S., S.C., M.E., S.M.D.), Victoria, Australia; Christchurch School of Medicine and Health Sciences (J.N.F.), New Zealand; Eastern Melbourne Neurosciences (C.B.), Australia; John Hunter Hospital (C.R.L., M.P.), Australia; University of Alberta (K.B.), Canada; Auckland City Hospital (P.A.B.), New Zealand; National Stroke Research Institute (G.A.D.), Melbourne, Australia; and University of Melbourne (G.A.D., S.M.D.), Australia.

Correspondence to Stephen M. Davis, Division of Neurosciences, Royal Melbourne Hospital, Grattan Street, Parkville 3050, Victoria, Australia. E-mail stephen.davis{at}mh.org.au

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 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.

Conclusion— 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.

Key Words: clinical outcomes • ischemic stroke • recanalization • reperfusion • thrombolysis