Plasminogen Activators The Old and the New Marschall

T hrombosis of a coronary or cerebral artery is the most common cause of mortality and morbidity in the developed nations.' The proximate cause is most often atherosclerosis, and the most appropriate intervention is its prevention. Much progress has been made in identifying the risk factors predisposing to atherosclerosis, and, perhaps because of their recognition, a significant decrease in the incidence of both stroke and myocardial infarction has occurred. However, coronary thrombosis remains a major clinical problem. Early dissolution of the thrombus by plasminogen activator therapy has become the most effective means of limiting myocardial damage. With the Food and Drug Administration's recent approval of tissue plasminogen activator (t-PA), the clinician now has available several agents for the treatment of acute coronary thrombosis. Three plasminogen activators are currently available in the United States: urokinase, streptokinase, and t-PA (the last two are FDA approved). Two more agents are on the horizon: acylated plasminogenstreptokinase activator complex (APSAC) and singlechain urokinase plasminogen activator (scu-PA). The economics and logistics of choosing a plasminogen activator have been discussed recently in detail.2-4 However, the information necessary for the physician to be able to choose among the various plasminogen activators-a direct clinical comparison-is lacking. Two large-scale clinical trials now underway, GISSI-II (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico) and ISIS-III (International Studies of Infarct Survival), will compare t-PA and streptokinase and will evaluate the concomitant use of anticoagulant and antiplatelet agents. Therefore, in this review, we do not recommend the use of a particular plasminogen activator, but we focus instead on the theoretical and practical considerations for the current development of new agents and discuss