Review of tenecteplase (TNKase) in the treatment of acute myocardial infarction

Abstract

TNKase is a genetically engineered variant of the alteplase molecule. Three different mutations result in an increase of the plasma half-life, of the resistance to plasminogen-activator inhibitor 1 and of the thrombolytic potency against platelet-rich thrombi. Among available agents in clinical practice, TNKase is the most fibrin-specific molecule and can be delivered as a single bolus intravenous injection. Several large-scale clinical trials have enrolled more than 27,000 patients with acute myocardial infarction, making the use of this drug truly evidence-based. TNKase is equivalent to front-loaded alteplase in terms of mortality and is the only bolus thrombolytic drug for which this equivalence has been formally demonstrated. TNKase appears more potent than alteplase when symptoms duration lasts more than 4 hours. Also, TNKase significantly reduces the rate of major bleeds and the need for blood transfusions. The efficacy of TNKase may be further improved by enoxaparin substitution for unfractionated heparin, provided that enoxaparin dose adjustment is made for patients more than 75 years old. Hitherto, the small available randomized studies and international clinical registries suggest that pre-hospital TNKase is as effective as primary angioplasty, thus laying the foundations for a new fibrinolytic, TNKase-based strategy as the backbone of reperfusion in acute myocardial infarction.

Guideline on the management of bleeding in patients on antithrombotic agents

“…Tenecteplase is a recombinant modified form of tPA with six amino acid substitutions causing increased half-life of c. 20 min, increased resistance to PAI-1 inhibition and increased fibrin specificity (Melandri et al, 2009). It is cleared mainly by metabolism in the liver.…”

Long-term clinical outcome of acute myocardial infarction according to the early revascularization method: a comparison of primary percutaneous coronary interventions and fibrinolysis followed by routine invasive treatment

“…An earlier start of treatment might be an important factor for this result. Finally, in our analysis all fibrinolysis patients received tenecteplase (Metalyze) as the thrombolytic agent, which is known to be the most fibrin-specific agent, and to cause less major bleeding complications, such as hemorrhagic stroke [12].…”

Expression of a Novel Chimeric-Truncated tPA in Pichia pastoris with Improved Biochemical Properties

“…Thrombolytic agents such as PAs present a routine treatment of AIS and one of its most important sub-categories, AMI, as well as vascular occlusion and pulmonary embolism [1]. However, PAs show different shortcomings related to their pharmacodynamics, pharmacokinetics and safety profiles, so the application in AIS was hindered [29,30]. Currently, only one rtPA, Actylase Ò , is a licensed pharmacological agent to treat selected patients with AIS [28].…”