Effects of Integrelin, a platelet glycoprotein IIb/IIIa receptor antagonist, in unstable angina: A randomized multicenter trial

Steven P. Schulman, Pascal J. Goldschmidt-Clermont, Eric J. Topol, Robert M. Califf, Frank I. Navetta, James T. Willerson, Nisha C. Chandra, Alan D. Guerci, James J. Ferguson, Roben A. Harrington, A. Michael Lincoff, Steven J. Yakubov, Paul F. Bray, Raymond D. Bahr, Christopher L. Wolfe, Paul G. Yock, H. Vernon Anderson, Thomas W. Nygaard, Steven J. Mason, Mark B. EffronAnil Fatterpacker, Stephen Raskin, Jack Smith, Lori Brashears, Patricia Gottdiener, Charles Du Mee, Michael M. Kitt, Gary Gerstenblith

Research output: Contribution to journalArticle

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Abstract

Background: Although aspirin is beneficial in patients with unstable angina, it is a relatively weak inhibitor of platelet aggregation. The effect of Integrelin, which inhibits the platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa, on the frequency and duration of Holter ischemia was evaluated in 227 patients with unstable angina. Methods and Results: Patients received intravenous heparin and standard anti-ischemic therapy and were randomized to receive oral aspirin and placebo Integrelin; placebo aspirin and low-dose Integrelin, 45 μg/kg bolus followed by a 0.5-μg · kg -1 · min -1 continuous infusion; or placebo aspirin and high-dose Integrelin, 90 μg/kg bolus followed by a 1.0-μg · kg -1 · min -1 constant infusion. Study drug was continued for 24 to 72 hours, and Holter monitoring was performed. Patients randomized to high-dose Integrelin experienced 0.24±0.11 ischemic episodes (mean±SEM) on Holter lasting 8.41±5.29 minutes over 24 hours of study drug infusion. Patients randomized to aspirin experienced a greater number (1.0±0.33, P<.05) and longer duration (26.2±9.8 minutes, P=.01) of ischemic episodes than the high-dose Integrelin group. There was no evidence of rebound ischemia after withdrawal of study drug. In 46 patients, platelet aggregation was rapidly inhibited by Integrelin in a dose-dependent fashion. The number of clinical events was small, and there were no bleeding differences in the three treatment arms. Conclusions: Intravenous Integrelin is well tolerated, is a potent reversible inhibitor of platelet aggregation, and added to full-dose heparin reduces the number and duration of Holter ischemic events in patients with unstable angina compared with aspirin.

Original languageEnglish (US)
Pages (from-to)2083-2089
Number of pages7
JournalCirculation
Volume94
Issue number9
DOIs
StatePublished - Jan 1 1996

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Keywords

  • angina
  • integrins
  • ischemia
  • platelets

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Schulman, S. P., Goldschmidt-Clermont, P. J., Topol, E. J., Califf, R. M., Navetta, F. I., Willerson, J. T., Chandra, N. C., Guerci, A. D., Ferguson, J. J., Harrington, R. A., Lincoff, A. M., Yakubov, S. J., Bray, P. F., Bahr, R. D., Wolfe, C. L., Yock, P. G., Vernon Anderson, H., Nygaard, T. W., Mason, S. J., ... Gerstenblith, G. (1996). Effects of Integrelin, a platelet glycoprotein IIb/IIIa receptor antagonist, in unstable angina: A randomized multicenter trial. Circulation, 94(9), 2083-2089. https://doi.org/10.1161/01.CIR.94.9.2083