After coronary thrombolysis and reperfusion, what next?

Thrombolytic therapy for the removal of intravascular thrombi was introduced when streptokinase was first given to humans 40 years ago, the same year the American College of Cardiology was founded. Streptokinase was first administered to patients with acute myocardial infarction in 1959. Today, thrombolytic therapy has been established to offer significant benefits to patients with acute myocardial infarction provided they are brought to medical attention early enough after the onset of symptoms. The two major agents, streptokinase and recombinant tissue-type plasminogen activator (rt-PA), have been shown to result in reperfusion of infarct-related arteries, to salvage ischemic myocardium, to improve myocardial performance and to reduce mortality. In spite of these impressive gains, this novel therapy has shortcomings. The interval from the start of thrombolytic treatment to coronary reperfusion varies significantly from patient to patient and may, at times, be too long to produce a real benefit in terms of salvage of ischemic myocardium. The rate of reocclusion lies somewhere between 10% and 20% and appears not to be influenced by concomitant heparin anticoagulation. The rate of bleeding complications even with the "fibrin-specific" rt-PA is higher than anticipated and may range from 10% to 30%. As a consequence, intensive efforts are being directed at the development of improved thrombolytic agents and for adjunctive therapy evaluating better anticoagulants than heparin and better antiplatelet agents than aspirin. This review is a status report summarizing where we are in thrombolytic therapy in acute myocardial infarction, where we need to improve treatment results and what is being done mainly at the preclinical level to bring about such improvements.