Tissue plasminogen activator: an evaluation of clinical efficacy in acute myocardial infarction

Recombinant tissue plasminogen activator (t-PA) is a synthetic fibrinolytic protein which activates plasminogen or converts plasminogen to plasmin specifically in the presence of fibrin. With its "clot-selectivity", t-PA is capable of lysing clots without having a significant effect on circulating plasminogen. In contrast, activation by streptokinase and urokinase is non-specific and affects circulating as well as thrombus plasminogen. These agents, therefore, have a greater potential to induce bleeding than does t-PA. Plasma levels of t-PA following intravenous administration are generally proportional to the dose, but there can be significant interpatient variation. The drug is eliminated primarily by hepatic metabolism and is then excreted in the urine. Half-life of circulating t-PA ranges from 2-8 minutes. Most clinical trials of t-PA have evaluated its use in acute myocardial infarction. Indeed, its current indication is for thrombolysis in evolving MI. Short-term benefits of t-PA administration include a prompt reperfusion and restoration of coronary artery patency in patients with total coronary artery occlusion. The degree to which the heart benefits from thrombolysis is unknown, but electrocardiographic changes, changes in cardiac enzymes and alterations in the pattern of chest pain indicate that rapid reperfusion may limit the size of the infarct. Overall, t-PA appears to be a relatively safe thrombolytic agent. Bleeding is the most significant adverse effect reported with t-PA administration. In most cases, however, bleeding has been minor. Other reported adverse effects include reperfusion arrhythmias, bradycardia, and chest pain. Allergic reactions were not observed in clinical trials.