R E V I E W Review of tenecteplase (TNKase) in the treatment of acute myocardial infarction Giovanni Melandri Fabio Vagnarelli Daniela Calabrese Franco Semprini Samuele Nanni Angelo Branzi Dipartimento Cardiovascolare, Università di Bologna, Italy Correspondence: Giovanni Melandri, Istituto di Cardiologia, Policlinico Sant’Orsola,Via Massarenti 9, 40138 Bologna, Italy Tel +39 051 6364528 Fax +39 051 344859 Email giovanni.melandri@aosp.bo.it 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. Keywords: tenecteplase, TNKase, myocardial infarction, alteplase Thrombolytic therapy versus primary angioplasty Acute myocardial infarction presenting with ST-segment elevation (STEMI) is usually precipitated by plaque disruption with coronary thrombosis. The quick recanalization by either thrombolysis (TBL) or primary angioplasty (P-PCI) is the most important way to improve the short- and long-term prognosis. Current American and European guide- lines “prefer” P-PCI, usually believed to achieve better coronary recanalization rates, prevent re-infarction and, ultimately, improve survival.1 However, many conceptual and practical items dispute this presumed superiority of P-PCI (Table 1). The claim that P-PCI leads to a mortality reduction has never been shown in any single trial and is only suggested by an overview of 23 small trials, with only 2 trials enrolling more than 1000 patients.2 Furthermore, this small advantage is no longer signiﬁcant when the comparison is made with the accelerated infusion of alteplase.3 Too many times have we observed the failure of such positive small meta-analyses, such as those evaluating the effects of nitrates or magnesium in acute myocardial infarction, or the efﬁcacy of angiotensin-II blockers to prevent atrial ﬁbrillation, or the efﬁcacy of aspirin to prevent eclampsia. The frequently quoted mortality reduction observed in patients treated with P-PCI in registries is largely biased both by the incapacity of statistical methods, such as the propensity score, to take into account important, intangible confounders, and by the entry in the P-PCI cohort of only those patients actually being treated and not those patients intended to treat.4 Vascular Health and Risk Management 2009:5 249–256 © 2009 Melandri et al, publisher and licensee Dove Medical Press Ltd.This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. 249