EVALUATION OF A PROLONGED INFUSION OF RECOMBINANT TISSUE-TYPE PLASMINOGEN-ACTIVATOR (DUTEPLASE) IN PREVENTING REOCCLUSION FOLLOWING SUCCESSFUL THROMBOLYSIS IN ACUTE MYOCARDIAL-INFARCTION

The hypothesis that an infusion of recombinant tissue-type plasminogen activator (rt-PA) maintained for up to 24 hours could prevent reocclusion after early coronary patency had been established was evaluated in patients with acute myocardial infarction. The rt-PA studied was an investigational double chain rt-PA (Duteplase(R), Burroughs Wellcome Co.), administered according to body weight. Coronary patency was documented in 139 of 213 patients who had 90-minute angiograms recorded after an initial lytic dose of rt-PA. In these responders a further 90-minute infusion at one third the initial lytic dose was given before assignment to 1 of 4 maintenance dose rates (0.0 12, 0.024, 0.036, 0.048 MIU/kg/hour) which were continued for the subsequent 9 to 21 hours. The principal end point was the status of the infarct-related coronary artery 12 to 24 hours after the start of therapy, and before termination of rt-PA, in patients with initially patent vessels at 90 minutes. Of the 103 responders with repeat angiograms after a 9 to 21 hour maintenance infusion of rt-PA, a total of 17 (16.50%) patients reoccluded across all doses administered. There was no significant relationship between the maintenance dose rate and the incidence of reocclusion. However, there was strong association between total dose of rt-PA administered and the incidence (16%) of serious or life-threatening bleeding exclusive of surgery. Other factors associated with serious bleeding included low body weight, female gender, and total duration of rt-PA infusion. Reocclusion was independent of the 90-minute Thrombolysis in Myocardial Infarction trial perfusion grade and diameter of infarct vessel. Rethrombosis after establishment of early patency after rt-PA remains a significant problem that is unaffected by sustained rt-PA infusion in doses that can be tolerated.