title: Equipoise among recanalization strategies.
abstract: Modern acute ischemic stroke therapy is based on the premise that recanalization and subsequent reperfusion are essential for the preservation of brain tissue and favorable clinical outcomes. We outline key issues that we think underlie equipoise regarding the comparative clinical efficacy of IV recombinant tissue-type plasminogen activator (rt-PA) and intra-arterial (IA) reperfusion therapies for acute ischemic stroke. On the one hand, IV rt-PA therapy has the benefit of speed with presumed lower rates of recanalization of large artery occlusions as compared to IA methods. More recent reports of major arterial occlusions treated with IV rt-PA, as measured by transcranial Doppler and magnetic resonance angiography, demonstrate higher rates of recanalization. Conversely, IA therapies report higher recanalization rates, but are hampered by procedural delays and risks, even failing to be applied at all in occasional patients where time to reperfusion remains a critical factor. Higher rates of recanalization in IA trials using clot-removal devices have not translated into improved patient functional outcome as compared to trials of IV therapy. Combined IV-IA therapy promises to offer advantages of both, but perhaps only when applied in the timeliest of fashions, compared to IV therapy alone. Where equipoise exists, randomizing subjects to either IV rt-PA therapy or IV therapy followed by IA intervention, while incorporating new interventions into the study design, is a rational and appropriate research approach.
authors.affiliation: Department of Neurology, UC Neuroscience Institute, University of Cincinnati Academic Health Center, Cincinnati, OH 45267-0525, USA. joseph.broderick@uc.edu
authors.forename: T A
authors.initials: TA
authors.lastname: Tomsick
authors.forename: P
authors.initials: P
authors.lastname: Khatri
authors.forename: T
authors.initials: T
authors.lastname: Jovin
authors.forename: B
authors.initials: B
authors.lastname: Demaerschalk
authors.forename: T
authors.initials: T
authors.lastname: Malisch
authors.forename: A
authors.initials: A
authors.lastname: Demchuk
authors.forename: M D
authors.initials: MD
authors.lastname: Hill
authors.forename: E
authors.initials: E
authors.lastname: Jauch
authors.forename: J
authors.initials: J
authors.lastname: Spilker
authors.forename: J P
authors.initials: JP
authors.lastname: Broderick
mesh_terms: D000208:Acute Disease; D000818:Animals; D002545:Brain Ischemia / Q000628:therapy*; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007261:Infusions, Intra-Arterial / Q000009:adverse effects / Q000379:methods; D007262:Infusions, Intravenous / Q000009:adverse effects / Q000379:methods; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015424:Reperfusion / Q000009:adverse effects / Q000379:methods*; D020521:Stroke / Q000628:therapy*; D057212:Therapeutic Equipoise; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator