Which thrombolytic agents have been considered for the treatment of acute ischemic stroke (AIS)?

Updated: Dec 31, 2017
  • Author: Wanda L Rivera-Bou, MD, FAAEM, FACEP; Chief Editor: Erik D Schraga, MD  more...
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Other IV thrombolytic agents have been considered for treatment of patients with AIS. Clinical trials of streptokinase were halted prematurely because of high rates of hemorrhage; therefore, this agent should not be used. [48] Tenecteplase appears promising as an effective thrombolytic agent, apparently causing fewer bleeding complications.

A prospective, nonrandomized, pilot study evaluated imaging-guided tenecteplase therapy with 0.1 mg/kg IV given 3-6 hours after ischemic stroke onset; control subjects were treated within 3 hours with 0.9 mg/kg IV of alteplase according to the standard selection criteria. [49] The study demonstrated that the former approach may have significant biologic efficacy, but in view of the imaging selection differences, it could not determine whether this approach has an enhanced therapeutic margin compared with the latter approach.

A subsequent randomized phase 2B trial compared the standard dose of alteplase (0.9 mg/kg) with tenecteplase (0.1 mg/kg or 0.25 mg/kg). [50] Patient were selected using CT perfusion imaging and with less than 6 hours after the onset of ischemic stroke. Tenecteplase (0.25 mg/kg) was superior to the lower dose and to alteplase achieving significant reperfusion and neurologic improvement without an increase in intracranial bleeding.

Desmoteplase, a fibrin-specific plasminogen activator, is a genetically engineered version of a clot-dissolving protein from vampire bats. Previous studies suggested that desmoteplase has clinical benefits when given within 3-9 hours of symptom onset, with magnetic resonance imaging (MRI) criteria used to identify those eligible for the trials on the basis of diffusion-perfusion mismatch. [51, 52] The completed phase III Desmoteplase in Acute Stroke Trial-2 (DIAS-2) did not confirm this suggested benefit. [53]


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