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 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 Metalyse® and front-loaded alteplase are associated with comparable rates of intracranial haemorrhage and total stroke. However, patients treated with 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 Metalyse® as with front-loaded alteplase. An appropriately weight-adjusted dose of the more fibrin-specific 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.
In ASSENT-2 the thirty-day mortality rates for Metalyse® and alteplase-treated patients were almost identical: 6.18% for Metalyse® and 6.15% for alteplase. The table shows the non-fatal in-hospital cardiac events and the use of procedures. After treatment with 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 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 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 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
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.