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.