Abstract
Thrombolytic therapy with pharmacologic agents is an exciting approach to the treatment of myocardial infarction. The results of several clinical studies indicate that perfusion can be restored with intravenous therapy and may be associated with a reduction in infarct size and improved left ventricular function. In a trial involving more than 11,000 patients thrombolytic therapy reduced acute and long term mortality. Pharmacologic thrombolysis, however, is not without problems. When administered intravenously, the agents currently available, streptokinase and urokinase, are associated with a relatively low recanalization rate as well as a risk of adverse effects, most commonly a systemic lytic state and risk of bleeding complications. Although intracoronary administration is associated with a higher rate of recanalization, the need for cardiac catheterization limits its applicability and results in a delay in the initiation of thrombolytic therapy (which diminishes salvage of myocardium). The trials assessing the existing agents have shown that time is a critical variable in the success of thrombolytic therapy. This had led investigators to focus more attention on intravenous agents that can be administered rapidly. The newer agents now under investigation, acylated streptokinase and single-chain urokinase, may represent improvements of currently available products and may offer potentially increased benefits. A fibrinogen-sparing agent, such as t-PA, in addition to being highly effective, may offer advantages through minimizing the systemic lytic effect. Additional randomized, controlled clinical trials currently are underway to determine the effect on mortality of this 'fibrinolytic' therapy as part of a total treatment regimen. The current status of our knowledge concerning thrombolytic therapy in acute myocardial infarction can be summarized as follows: 1. Transmural (that is, Q wave) myocardial infarction usually is caused by an obstructing coronary thrombus. 2. The thrombus can be lysed with intravenous therapy in the majority of cases, particularly with newer, well-tolerated fibrin-specific agents. 3. There is considerable evidence suggesting that reperfusion reduces the acute morbidity and mortality when therapy is administered successfully within the initial 3 to 4 hours (and possibly up to 6 hours) after onset of symptoms. 4. Data on long term prognosis after thrombolysis are very encouraging, although limited. 5. Conventional agents lead to significant fibrinogen depletion and therefore an increased risk of bleeding; the new fibrin-selected agents cause less fibrinogen degradation and may reduce the risk of hemorrhagic complications. 6. The incidence and optimal means of prevention of restenosis and reinfarction following successful thrombolysis are unclear at present. Mechanical recanalization (PTCA) in conjunction with thrombolysis is under investigation.