Adjunctive Medical Therapies for Acute Stroke Thrombolysis

Abstract

See related article, p 2381 Beyond intravenous tissue-type plasminogen activator (IV-tPA), the field of acute ischemic stroke suffers from a lack of safe and effective treatments aimed at both proximal thrombus dissolution and return of flow to the microcirculation. Larger thrombi have notoriously proven to be resistant to IV-tPA lysis with recanalization rates in the range of only 13% to 20%.1,2 Even if endovascular treatment of ischemic stroke is proven to improve clinical outcomes, there will still be many patients with residual partial or complete occlusion after IV-tPA alone suffering ischemia, whereas waiting for catheter rescue. The lag between endovascular team activation and groin puncture requires precious minutes-to-hours for team assembly. For example, in the Interventional Management of Stroke-3 clinical trial, the average time from tPA bolus to intraarterial therapy was 2.2 hours.3 Therefore, development of combination therapies for acute ischemic stroke that can be delivered quickly in the emergency setting is crucial. Adjunctive therapies to IV-tPA can take many forms to include medical or mechanical, but any of these must be started early to augment the effect of IV-tPA.4 Ongoing strategies that are in either phase II or III clinical trials include thrombin-inhibition, sonothrombolysis, and platelet-inhibition. In this issue of Stroke , the results of the Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke–Enhanced Regimen (CLEAR-ER) study are published.5 This is a multicenter, double-blind, randomized phase II safety trial of 0.9 mg/kg 0 to 3 hours IV-tPA versus 0.6 mg/kg 0 to 3 hours IV-tPA+IV eptifibatide (bolus 135 mcg/kg and 2-hour infusion at 0.75 mcg/kg per minute). CLEAR-ER sought to estimate the safety and efficacy of combination GP Ib/IIIa+reduced dose IV-tPA when delivered to hyperacute ischemic stroke. The trial was sponsored by the National Institutes of Health/National Institute of …