EFFECTIVENESS OF MULTIPLE BOLUS ADMINISTRATION OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR IN ACUTE MYOCARDIAL-INFARCTION

The feasibility and possible advantages of intravenous bolus administration of recombinant tissue-type plasminogen activator (rt-PA) were investigated in 26 consecutive patients with early (<6 hours) evolving acute myocardial infarction. Either an intravenous infusion of 40 clot-lysis megaunits (cIMU) double-chain rt-PA over 1.5 hours followed by 20 cIMU over 5 hours (infusion group, n = 12) or 4 intravenous bolus injections of 10 cIMU at 20 minute intervals (bolus group, n = 14) were randomly administered. Coronary arteriography was performed before and at regular predefined intervals up to 90 minutes from the start of rt-PA administration, and at 24 hours. Acute recanalization of the infarct-related coronary artery was demonstrated in 7 of 12 patients (58%; 95% confidence interval 28 to 85%) in the infusion group and 11 of 14 patients (79%; 95% confidence interval 49 to 95%) in the bolus group (difference not significant). Two patients in the bolus group had reoccluded by 24 hours. Mean time from the start of rt-PA to patency of the infarct-related coronary artery was 39 ± 6 (standard error of the mean) minutes in the infusion group and 28 ± 6 minutes in the bolus group (p = 0.2). There were no significant differences in the minimum infarct-related coronary artery luminal diameter measured by computerized quantitative arteriography between the infusion group and the bolus group at 90 minutes or at 24 hours. Resolution of ST-segment elevation assessed by continuous electrocardiographic monitoring over the first 24 hours appeared to occur sooner in recanalized patients in the bolus group (2.8 ± 0.5 hours) than in the infusion group (5.5 ± 2.1 hours, p = 0.3). The period during which the plasma fibrinogen remained below pretreatment levels was longer in the infusion group (54 ± 7 hours) compared to the bolus group (29 ± 6 hours, p = 0.01). Thus, multiple bolus rt-PA appears to result in earlier recanalization of the infarct-related coronary artery and in a shorter duration of acute ischemia compared to an intravenous infusion. The smaller total dose of rt-PA results in less prolonged fibrinogenolysis. © 1990.