A COMPARISON OF CONTINUOUS-INFUSION OF ALTEPLASE WITH DOUBLE-BOLUS ADMINISTRATION FOR ACUTE MYOCARDIAL-INFARCTION

Background Accelerated infusion of alteplase (tissue plasminogen activ ator) over a period of 90 minutes induces more rapid lysis of coronary -artery thrombi than a 3-hour infusion. With two bolus doses of altepl ase, further shortening the duration of administration, complete reper fusion was achieved in more than 85 percent of the patients in initial angiographic studies. We tested the hypothesis that double-bolus alte plase is at least as effective as accelerated infusion. Methods In 398 hospitals, 7169 patients with acute myocardial infarction were random ly assigned to weight-adjusted, accelerated infusion of 100 mg of alte plase or to a bolus of 50 mg of alteplase over a period of 1 to 3 minu tes followed 30 minutes later by a second bolus of 50 mg (or 40 mg for patients who weighed less than 60 kg). The primary end point was deat h from any cause at 30 days. The trial was stopped prematurely because of concern about the safety of the double-bolus injection. Results Th irty-day mortality was higher in the double-bolus group than in the ac celerated-infusion group: 7.98 percent as compared with 7.53 percent, The absolute difference was 0.44 percent, with a one-sided 95 percent upper boundary of 1.49 percent, which exceeded the prespecified upper limit of 0.40 percent to indicate equivalence in 30-day mortality betw een the two regimens. The respective rates of any stroke and of hemorr hagic stroke were 1.92 and 1.12 percent after double-bolus alteplase, as compared with 1.53 and 0.81 percent after an accelerated infusion o f alteplase (P = 0.24 and P = 0.23, respectively). Conclusions Double- bolus alteplase was not shown to be equivalent, according to the presp ecified criteria, to accelerated infusion with regard to 30-day mortal ity, There was also a slightly higher rate of intracranial hemorrhage with the double-bolus method. Therefore, accelerated infusion of altep lase over a period of 90 minutes remains the preferred regimen. (C) 19 97, Massachusetts Medical Society.