Strategies for administration of tissue plasminogen activator

Since the first patient was treated with recombinant tissue plasminogen activator (t-PA) in 1984, there has been remarkable progress in our understanding of optimal methods for administration of this thrombolytic agent. As a background and foundation to clinical trials, the experimental data for bolus t-PA, adjunctive treatments and new plasminogen activators for more optimal thrombolysis are reviewed. The major findings in clinical evaluation for acute myocardial infarction to date include (1) substantial mortality reduction and improvement in cardiac function; (2) an excess of serious bleeding complications at high doses (150 mg) of t-PA; (3) rapid infarct vessel recanalization with an accelerated "front-loaded" regimen; (4) the importance of conjunctive intravenous heparin; and (5) the potential for new, combined plasminogen activator therapies. The recent data, collectively, have set the stage for a new greater than 30,000 patient mortality reduction trial entitled Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO).