Assessing reperfusion and recanalization as markers of clinical outcomes after intravenous thrombolysis in the echoplanar imaging thrombolytic evaluation trial (EPITHET).
OBJECTIVE
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.
De Silva
Deidre A
DA
Division of Neurosciences, Royal Melbourne Hospital, Grattan Street, Parkville 3050, Victoria, Australia.
Fink
John N
JN
Christensen
Soren
S
Ebinger
Martin
M
Bladin
Christopher
C
Levi
Christopher R
CR
Parsons
Mark
M
Butcher
Ken
K
Barber
P Alan
PA
Donnan
Geoffrey A
GA
Davis
Stephen M
SM
D002404:Catheterization / Q000379:methods / Q000592:standards; D002548:Cerebral Revascularization / Q000379:methods / Q000592:standards; D004311:Double-Blind Method; D017352:Echo-Planar Imaging / Q000379:methods / Q000592:standards*; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D007275:Injections, Intravenous; D011446:Prospective Studies; D015424:Reperfusion / Q000592:standards*; D020521:Stroke / Q000188:drug therapy / Q000601:surgery; D015912:Thrombolytic Therapy / Q000379:methods / Q000592:standards*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator