AN ANGIOGRAPHIC ASSESSMENT OF ALTEPLASE - DOUBLE-BOLUS AND FRONT-LOADED INFUSION REGIMENS IN MYOCARDIAL-INFARCTION

Background This study was designed to investigate the efficacy of alte plase double-bolus dosing compared with the front-loaded 90-minute inf usion regimen in patients with acute myocardial infarction. Recent pil ot studies have suggested that bolus dosing may provide improved effic acy in establishing early, complete, and sustained potency of the infa rct-related artery in the thrombolytic treatment of acute myocardial i nfarction. Methods and Results in this multicenter, randomized, open-l abel trial, 461 patients with acute myocardial infarction received 100 mg alteplase as a front-loaded 90-minute infusion (15 mg bolus, then 50 mg over a 30-minute period, then 35 mg over a 60-minute period) or double bolus (two 50 mg bolus injections 30 minutes apart). All patien ts also received intravenous heparin and oral aspirin during and after alteplase treatment. The 90-minute angiographic patency rates were 74 .5% in the double-bolus group and 81.4% in the infusion group (p = 0.0 8). Patency rates were also comparable for the two groups at 60 minute s (76.8% vs 77.5%) and 24 hours (95.5% vs 93.5%) after initiation of t reatment. In-hospital mortality rates were 4.5% in the bolus group and 1.3% in the infusion group (p = 0.04); 30-day mortality rates were 4. 5% and 1.7%, respectively (p = NS). The two-groups were comparable in frequency of all other adverse events. Conclusions Double-bolus altepl ase administration produced reperfusion rates comparable to front-load ed infusion, but in-hospital acid 30-day mortality rates were higher i n the double-bolus group. These findings are in agreement with those o f the COBALT megatrial, which also reported a trend to higher mortalit y rates with double-bolus dosing.