Evaluation of a weight-adjusted single-bolus plasminogen activator in patients with myocardial infarction: A double-blind, randomized angiographic trial of lanoteplase versus alteplase

Peter Den Heijer, Frank Vermeer, Ettore Ambrosioni, Zygmunt Sadowski, José L. López-Sendón, Rainer Von Essen, Philippe Beaufils, Udho Thadani, Jennifer Adgey, Luc Pierard, Jeffrey Brinker, Richard F. Davies, Richard W. Smalling, Lars Wallentin, Abraham Caspi, Andreas Pangerl, Linda Trickett, Cynthia Hauck, David Henry, Paul Chew

Research output: Contribution to journalArticle

Abstract

Background - Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. Methods and Results - In TIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double- blind, randomized, double-placebo angiographic trial, evaluated the dose- response relationship and safety of single-bolus, weight-adjusted lanoteplase. Patients (n=602) presenting within 6 hours of acute myocardial infarction were randomized and treated with either a single-bolus injection of lanoteplase (15, 30, 60, or 120 kU/kg) or accelerated alteplase. The primary objective was to determine TIMI grade flow at 60 minutes. Angiographic assessments were also performed at 90 minutes and on days 3 to 5. Follow-up was continued for 30 days. Lanoteplase achieved its primary objective, demonstrating a dose-response in TIMI grade 3 flow at 60 minutes (23.6% to 47.1% of subjects, P<0.001). Similar results were observed at 90 minutes (26.1% to 57.1%, P<0.001). At 90 minutes, coronary patency (TIMI 2 or 3) increased across the dose range up to 83% of subjects at 120 kU/kg lanoteplase compared with 71.4% with alteplase. Thus, at this dose, lanoteplase was superior to alteplase in restoring coronary patency (difference, 12%; 95% CI, 1% to 23%). The early safety experience in this study suggests that lanoteplase was well tolerated at all doses with safety comparable to that of alteplase. Conclusions - Lanoteplase, a single-bolus, weight-adjusted agent, increased coronary patency at 60 and 90 minutes in a dose-dependent fashion. Coronary patency at 90 minutes was achieved more frequently with 120 kU/kg lanoteplase than alteplase. In this study, safety with lanoteplase and alteplase was comparable. InTIME-II, a worldwide mortality trial, will evaluate efficacy and safety with this promising new agent.

Original languageEnglish (US)
Pages (from-to)2117-2125
Number of pages9
JournalCirculation
Volume98
Issue number20
DOIs
StatePublished - Nov 17 1998

Keywords

  • Myocardial infarction
  • Plasminogen activators
  • Reperfusion
  • Thrombolysis
  • Trials

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Den Heijer, P., Vermeer, F., Ambrosioni, E., Sadowski, Z., López-Sendón, J. L., Von Essen, R., Beaufils, P., Thadani, U., Adgey, J., Pierard, L., Brinker, J., Davies, R. F., Smalling, R. W., Wallentin, L., Caspi, A., Pangerl, A., Trickett, L., Hauck, C., Henry, D., & Chew, P. (1998). Evaluation of a weight-adjusted single-bolus plasminogen activator in patients with myocardial infarction: A double-blind, randomized angiographic trial of lanoteplase versus alteplase. Circulation, 98(20), 2117-2125. https://doi.org/10.1161/01.CIR.98.20.2117