RANDOMIZED COMPARISON OF CORONARY THROMBOLYSIS ACHIEVED WITH DOUBLE-BOLUS RETEPLASE (RECOMBINANT PLASMINOGEN-ACTIVATOR) AND FRONT-LOADED, ACCELERATED ALTEPLASE (RECOMBINANT TISSUE-PLASMINOGEN ACTIVATOR) IN PATIENTS WITH ACUTE MYOCARDIAL-INFARCTION

Background The therapeutic benefit of thrombolytic therapy has been sh own to correlate directly with completeness (TIMI grade 3 flow) and sp eed of reperfusion of the infarct-related coronary artery. The purpose of the RAPID II study was to determine whether a double-bolus regimen of reteplase, a recently developed deletion mutant of wild-type tissu e plasminogen activator, could improve 90-minute coronary artery paten cy rates achieved with the most successful standard regimen, an ''acce lerated'' front-loaded infusion of alteplase. Methods and Results Thre e hundred twenty-four patients with acute myocardial infarction were r andomized to receive (along with intravenous heparin and aspirin) eith er a 10 plus 10 megaunits double bolus of reteplase or front-loaded al teplase. The primary end point of ''patency at 90 minutes, graded acco rding to the TIMI classification'' was centrally assessed in a blinded fashion. Infarct-related coronary artery patency (TIMI grade 2 or 3) and complete patency (TIMI grade 3) at 90 minutes after the start of t hrombolytic therapy were significantly higher in the reteplase-treated patients (TIMI grade 2 or 3: 83.4% versus 73.3% for front-loaded alte plase-treated patients, P=.03; TIMI grade 3: 59.9% versus 45.2%, P=.01 ). At 60 minutes, the incidence of both, patency and complete patency, was also significantly higher in reteplase-treated patients (reteplas e versus alteplase, TIMI grade 2 or 3: 81.8% versus 66.1%, P=.01; TIMI grade 3: 51.2% versus 37.4%, P<.03). Reteplase-treated patients requi red fewer acute additional coronary interventions (13.6% versus 26.5%, P<.01); and 35-day mortality was 4.1% for reteplase and 8.4% for alte plase (P=NS). There were no significant differences between reteplase and alteplase in bleedings requiring a transfusion (12.4% versus 9.7%) or hemorrhagic stroke (1.2% versus 1.9%).Conclusions Reteplase, when given as a double bolus of 10 plus 10 megaunits to patients with acute myocardial infarction, achieves significantly higher rates of early r eperfusion of the infarct-related coronary artery and requires signifi cantly fewer acute coronary interventions than front-loaded alteplase without an apparent increased risk of complications.