Background Accelerated infusion of alteplase (tissue plasminogenactivator) over a period of 90 minutes induces more rapid lysisof coronary-artery thrombi than a 3-hour infusion. With twobolus doses of alteplase, further shortening the duration ofadministration, complete reperfusion was achieved in more than85 percent of the patients in initial angiographic studies.We tested the hypothesis that double-bolus alteplase is at leastas effective as accelerated infusion.
Methods In 398 hospitals, 7169 patients with acute myocardialinfarction were randomly assigned to weight-adjusted, acceleratedinfusion of 100 mg of alteplase or to a bolus of 50 mg of alteplaseover a period of 1 to 3 minutes followed 30 minutes later bya second bolus of 50 mg (or 40 mg for patients who weighed lessthan 60 kg). The primary end point was death from any causeat 30 days. The trial was stopped prematurely because of concernabout the safety of the double-bolus injection.
Results Thirty-day mortality was higher in the double-bolusgroup than in the accelerated-infusion group: 7.98 percent ascompared with 7.53 percent. The absolute difference was 0.44percent, with a one-sided 95 percent upper boundary of 1.49percent, which exceeded the prespecified upper limit of 0.40percent to indicate equivalence in 30-day mortality betweenthe two regimens. The respective rates of any stroke and ofhemorrhagic stroke were 1.92 and 1.12 percent after double-bolusalteplase, as compared with 1.53 and 0.81 percent after an acceleratedinfusion of alteplase (P = 0.24 and P = 0.23, respectively).
Conclusions Double-bolus alteplase was not shown to be equivalent,according to the prespecified criteria, to accelerated infusionwith regard to 30-day mortality. There was also a slightly higherrate of intracranial hemorrhage with the double-bolus method.Therefore, accelerated infusion of alteplase over a period of90 minutes remains the preferred regimen.
Source Information
Dr. Van de Werf, as chairman of the trial, assumes full responsibility for the overall content and integrity of the manuscript.Presented in part at the 18th Congress of the European Society of Cardiology, Birmingham, United Kingdom, August 25–29, 1996, and the 69th Scientific Sessions of the American Heart Association, New Orleans, November 10–13, 1996.
Address reprint requests to Dr. Frans Van de Werf at the Department of Cardiology, Gasthuisberg University Hospital, Herestraat 49, B-3000 Leuven, Belgium.
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