Bolus, front-loaded, and accelerated thrombolytic infusions for myocardial infarction and pulmonary embolism

Abstract

Thrombolytic therapy decreases mortality in patients with acute myocardial infarction and is now widely used in such patients. The choice of which thrombolytic agent to use in such patients, either streptokinase or recombinant tissue plasminogen activator (rt-PA), is based on regional preferences. The standard dose of streptokinase is 1.5 million units over 60 min, and the dose of rt-PA that is commonly used is 100 mg over 3 h. Experiments in animals have demonstrated that rt-PA produces continuing thrombolysis after it is cleared from the circulation and that thrombolysis is both increased and accelerated and bleeding is reduced when rt-PA is administered over a short time period. Based on these studies, there have been a number of recent trials examining alternative dosage regimens for rt-PA (bolus, front-loaded, and accelerated) in patients with myocardial infarction. To date, there is no convincing evidence that such regimens are superior to the more traditional rt-PA regimen. Future randomized trials will determine whether attempts to optimize rt-PA regimens will result in more efficacious treatment regimens. Interest in the use of thrombolytic therapy for patients with acute pulmonary embolism has been rekindled. The traditional 12- to 24-h regimens of streptokinase and urokinase are not optimal because of their logistic complexity and associated hemorrhagic complications. Clinical studies have demonstrated that rt-PA, 100 mg over 2 h, is an effective thrombolytic agent in patients with acute pulmonary embolism. In a recent double-blind trial in patients with acute pulmonary embolism, rt-PA, 0.6 mg/kg infused over 2 min, improved pulmonary perfusion. This bolus regimen is attractive because it is simple to administer. Future studies will compare the relative efficacy and safety of these two rt-PA regimens in patients with acute pulmonary embolism.