Alteplase. A reappraisal of its pharmacological properties and therapeutic use in acute myocardial infarction

Abstract

Alteplase (recombinant tissue-type plasminogen activator) stimulates the fibrinolysis of blood clots by converting plasminogen to plasmin. The efficacy of intravenous alteplase in the early treatment of patients with acute myocardial infarction has been unequivocally proven, and recent results from the GUSTO trial indicate a significant advantage in 30-day survival for alteplase in an accelerated dosage regimen (< or = 100mg infused over 90 minutes rather than 3 hours) over streptokinase. The advantage of the accelerated alteplase dosage regimen seems to be maintained for at least 1 year. The role of heparin as adjunctive therapy to thrombolysis remains to be fully defined but heparin administration appears to be more important in conjunction with alteplase than with streptokinase. Ideally, patients should receive alteplase as soon as possible after the onset of symptoms of acute myocardial infarction and, while therapy is most beneficial when administered early, survival is improved when the drug is administered up to 12 hours after symptom onset. The accelerated regimen of alteplase used in the GUSTO trial demonstrated a survival advantage in patients < or = 75 as well as those > 75 years of age which was at least as great as that seen with streptokinase. Similarly, alteplase reduces mortality in patients with both anterior and inferior infarctions; however, those with anterior wall infarctions show an improved outcome over those with inferior infarcts. On the basis of pharmacoeconomic analysis of GUSTO data, the accelerated alteplase regimen cost an estimated additional $US32,678 per year of life saved compared with a conventional streptokinase regimen. Cumulative 1-year costs were greater in patients who received the accelerated alteplase regimen but survival was significantly greater than in patients who received streptokinase. No difference in quality of life was evident in patients who received either treatment. The incidence of major haemorrhage associated with alteplase therapy appears to be similar to that seen with other fibrinolytic agents, increasing with increasing dose; however, the risk of stroke, particularly haemorrhagic stroke, is higher with alteplase than with streptokinase. Thus, alteplase has become firmly established as a first-line option in the management of acute myocardial infarction. On the basis of accumulated evidence, the greatest risk reduction with alteplase therapy may be in certain high risk groups, such as those with anterior infarcts, selected elderly patients and those who present late after symptom onset.