Tenecteplase: a review of its pharmacology and therapeutic efficacy in patients with acute myocardial infarction.
Tenecteplase is a triple combination mutant variant of alteplase with high fibrin specificity and resistance to plasminogen activator inhibitor-1. The reduced rate of systemic clearance of the drug relative to alteplase allows tenecteplase to be given by rapid bolus injection to patients with acute myocardial infarction (AMI) with ST segment elevation. The efficacy of tenecteplase in AMI has been demonstrated in a phase I dose-ranging trial [Thrombolysis in Myocardial Infarction (TIMI) 10A], a nonblind phase II comparison with alteplase (TIMI 10B), and a randomized double-blind phase III comparison with alteplase in 16 949 patients [the second Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) trial]. Patients also received aspirin and intravenous heparin in all trials. In TIMI 10A and 10B, TIMI grade 3 coronary flow was achieved after 90 minutes in 54.3 to 65.8% of patients receiving tenecteplase 30, 40 or 50 mg; in TIMI 10B, grade 3 flow was reported in 62.7% patients receiving alteplase (</=100mg by front-loaded infusion over 90 minutes). Thirty-day mortality was similar with bodyweight-adjusted intravenous bolus doses of tenecteplase 30 to 50mg and front-loaded 90-minute infusion of alteplase in ASSENT-2 (approximately 6.2%). Rates of reinfarction and cardiogenic shock were also similar between groups, although mortality was reduced with tenecteplase in patients receiving treatment more than 4 hours after onset of symptoms (7 vs 9.2%; p = 0.018). Preliminary data show maintenance of the similarity between groups over 1 year (approximate 10.2% mortality in both groups), with loss of statistical significance between groups in patients treated late. ASSENT-2 showed the risks of intracranial hemorrhage (0.93%) and stroke (all causes) [1.78%] with tenecteplase to be similar to those with alteplase (0.94 and 1.66%, respectively). The rate of noncerebral bleeding was lower with tenecteplase than with alteplase (26.43 vs 28.95%; p = 0.0003). No causal link has been demonstrated between tenecteplase and allergic reactions in patients.


CONCLUSIONS
Bolus tenecteplase is an effective thrombolytic agent, suitable for first-line use in patients with AMI with ST segment elevation. Results to date show overall efficacy and tolerability profiles similar to those of alteplase, with comparable mortality after 1 year's follow-up. The apparent advantages of tenecteplase (reduced mortality in patients receiving late treatment and reduced incidence of noncerebral bleeding complications) in ASSENT-2 are of interest and merit further attention. The full implications of the availability of bolus administration and its potential clinical advantages over the currently widely used infusion regimens, together with the effect on outcomes of addition of tenecteplase to platelet glycoprotein IIb/IIIa inhibition, are currently under investigation.
Dunn
C J
CJ
Adis International Inc., Langhorne, Pennsylvania, USA. demail@adis.com
Goa
K L
KL
D000208:Acute Disease; D000818:Animals; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D007275:Injections, Intravenous; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy*; D055502:Secondary Prevention; D000077785:Tenecteplase; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control; D010959:Tissue Plasminogen Activator / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase