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.