Tenecteplase for Acute Ischemic Stroke: Current Evidence and Practical Considerations
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LEADING ARTICLE
Tenecteplase for Acute Ischemic Stroke: Current Evidence and Practical Considerations Alejandro A. Rabinstein1 · Esteban Golombievski2 · Jose Biller2
© Springer Nature Switzerland AG 2020
Abstract Tenecteplase offers pharmacological advantages over alteplase, and growing evidence supports its consideration for the treatment of patients with acute ischemic stroke. Its ease of administration as a single bolus makes it a preferable agent for patients who need to be urgently transported to a comprehensive stroke center for endovascular therapy (drip and ship) and for patients first evaluated at comprehensive stroke centers who are eligible for endovascular intervention (combined intravenous and endovascular approach). Recent randomized controlled trials indicated that the efficacy of tenecteplase may be similar to that of alteplase in patients with mild strokes and that it is superior to alteplase for patients with more severe strokes from a large vessel occlusion. Cumulative evidence currently favors the use of the 0.25 mg/kg dose. While tenecteplase has not been approved by regulatory agencies in the USA or the EU for the treatment of acute ischemic stroke, ongoing trials and additional clinical experience from countries where it is already being used in practice will likely clarify the role of tenecteplase for the acute management of ischemic stroke in the near future.
Key Points
1 Introduction
Growing evidence supports the consideration of tenecteplase as an alternative to alteplase for the treatment of patients with acute ischemic stroke.
Alteplase has been used for the treatment of acute ischemic stroke for nearly 25 years and remains the only approved thrombolytic agent for this indication [1]. Other thrombolytic drugs have been tested in acute stroke with variable results. Early research with streptokinase had to be stopped because of excessive bleeding complications, and subsequent studies with desmoteplase in extended time windows failed to achieve positive results. Instead, tenecteplase has consistently showed good safety and efficacy that has been at least comparable—if not superior—to that of alteplase [2–6]. Tenecteplase is a genetically modified variant of alteplase with three point mutations bioengineered to enhance its affinity to clot-bound fibrin and extend its duration of action to allow for administration as a single bolus [7, 8]. Compared with alteplase, tenecteplase has 14-fold greater specificity for fibrin, 80-fold increased resistance to plasminogen activator inhibitor-1 (PAI-1) and a much longer half-life (circulating half-life 22 min vs. 4 min and terminal half-life 2 vs. 1 h) [8]. Experimental studies have shown that tenecteplase produces faster and more potent lysis of clotbound fibrin (properties that would increase the chances of recanalization) with less consumption of fibrinogen, plasminogen, and alpha-2 antiplasmin (properties that would
Studies indicate that tenecteplase appears comparable to alteplase for patients with milder strokes and superior to altepl
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