Efficacy and safety
Speed is of the essence
The amount of tissue salvageable in myocardial infarction is inversely related to the duration of coronary artery occlusion up to about 5 hours, when myocardial ischaemia becomes irreversible. Very substantial myocardial salvage, and therefore saving of life, is possible if reperfusion therapy is started within 2 hours of the onset of symptoms, and especially within the first “golden” hour.
Single-bolus Tenecteplase (TNK-tPA, Metalyse®) is equivalent to front-loaded alteplase with respect to 30-day mortality and the combined endpoint of mortality or non-fatal stroke. This mortality benefit is consistent across all patient subgroups. It is not affected by age, infarct location, or history of hypertension, diabetes or previous myocardial infarction.
Single-bolus Tenecteplase (TNK-tPA, Metalyse®) and front-loaded alteplase are associated with comparable rates of intracranial haemorrhage and total stroke. However, patients treated with Tenecteplase (TNK-tPA, Metalyse®) experience a significantly lower rate of major non-cerebral bleeding events and require fewer blood transfusions than those treated with alteplase. Sub-group analysis indicates that high-risk patients can be treated at least as safely with Tenecteplase (TNK-tPA, Metalyse®) as with front-loaded alteplase. An appropriately weight-adjusted dose of the more fibrin-specific Tenecteplase (TNK-tPA, Metalyse®) therefore offers a safety benefit over front-loaded alteplase in the treatment of acute myocardial infarction.
The risk of complications due to thrombolytic therapy is very low the risk to induce a intracranial haemorrhage is <1%. Early thrombolysis may reduce the risk of death by up to 50%. Doctors should weigh up the relative contraindications when considering the benefits of thrombolytic therapy.
Frans Van de Werf - Benefits of Metalyse
In ASSENT-2 the thirty-day mortality rates for Tenecteplase (TNK-tPA, Metalyse®) and alteplase-treated patients were almost identical: 6.18% for Tenecteplase (TNK-tPA, Metalyse®) and 6.15% for alteplase. The table shows the non-fatal in-hospital cardiac events and the use of procedures. After treatment with Tenecteplase (TNK-tPA, Metalyse®), significantly fewer patients were in a Killip class higher than 1 (P=0.026) or underwent bypass surgery (P=0.049) compared with those treated with alteplase. No other significant differences were seen.
The results of ASSENT-2, therefore, confirm that single-bolus Tenecteplase (TNK-tPA, Metalyse®) is equivalent to front-loaded alteplase in the treatment of acute myocardial infarction with respect to the 30-day outcomes for mortality and the combined outcome of mortality or non-fatal stroke. Rates of mortality and combined outcome of mortality or non-fatal stroke were consistent among pre-specified subgroups including age, infarct location, and history of previous myocardial infarction.
Early controlled clinical trials indicated that the most frequent adverse reaction associated with Tenecteplase (TNK-tPA, Metalyse®), as with other fibrinolytic agents, is bleeding. In the large-scale ASSENT-2 mortality trial, the rate of intracranial haemorrhage was similar with both Tenecteplase (TNK-tPA, Metalyse®) and alteplase: 0.9% (relative risk 0.99; 95% confidence interval 0.727-1.35).
Frequency of in-hospital cardiac events and procedures in ASSENT-2
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The table shows the incidence of stroke and intracranial haemorrhage at 30 days in the ASSENT-1 trial. The total stroke rate (1.5%) was similar to that observed in other trials of thrombolytic therapy, as was the overall safety profile.
ASSENT-1: Safety assessment of tenecteplase in acute myocardial infarction
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References:
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Cannon et al. Circulation 1998; 98 (25): 2805-2814.
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ASSENT-2 Investigators. Lancet 1999; 354 (9180): 716-722.
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Cannon et al. Circulation 1997; 95 (2): 351-356.