Thrombolytic Agents for Acute Myocardial Infarction

Abstract

There are five agents [streptokinase (SK), anisoylated plasminogen-streptokinase complex (APSAC), urokinase (UK), recombinant tissue plasminogen activator (rt-PA), and pro-urokinase (r pro-UK)] that have been under evaluation for the treatment of an acute evolving myocardial infarction. All are either indirect or direct activators of plasminogen; they all convert the latter to the proteolytic enzyme plasmin by cleaving the ATg560-Va1561 bond; and all, when used properly, are effective in dissolving recent thrombi and emboli. Each has advantages and disadvantages, but none have established their superiority over the others as yet. This conclusion, while dependent on incomplete data and subject to change, is based on their comparative effects when administered intravenously in patients with acute evolving myocardial infarctions. STREPTOKINASE (SK)Streptokinase, the bacterial protein that reacts immediately on a one-to-one basis with human plasminogen to form a potent and very efficient plasminogen activator, is the least expensive of the agents. The earlier it is administered after the onset of the symptoms of a myocardial infarction, the higher is the frequency of reperfusion (2, 4,2 1,40, 50,7 1,9 1, 106, 1 1 1, 1 15). During the most critical period, i.e., the first 3 h, a reasonable estimate is 65% (100, 104). Great difficulties exist in accurately establishing the incidence or adequacy of reperfusion associated with the administration of thrombolytic agents intravenously during the first 3 h following symptom onset. The estimate given is based primarily on reperfusion rates observed with post-treatment angiograms only (2, 4, 50, 91, 11 1). Pretreatment angiograms were not done in all but one of these studies since the procedure, when added to the time of amval at the catheterization laboratory following symptom onset, prohibits treatment of the vast majority of patients within the first 3 h. The use of angiography, while currently the best method for measuring perfusion, has serious limitations: in the presence of a pathologic process with ongoing necrosis it does not measure flow rates or its adequacy or the efficacy of the more distal perfusion, and the observations are made at