Effects of Integrelin, a platelet glycoprotein IIb/IIIa receptor antagonist, in unstable angina

A randomized multicenter trial

Steven P. Schulman, Pascal 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. Effron & 8 others Anil Fatterpacker, Stephen Raskin, Jack Smith, Lori Brashears, Patricia Gottdiener, Charles Du Mee, Michael M. Kitt, Gary Gerstenblith

Research output: Contribution to journalArticle

115 Citations (Scopus)

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
Pages (from-to)2083-2089
Number of pages7
JournalCirculation
Volume94
Issue number9
StatePublished - Nov 7 1996
Externally publishedYes

Fingerprint

Integrin beta3
Platelet Glycoprotein GPIIb-IIIa Complex
Unstable Angina
Multicenter Studies
Aspirin
Platelet Aggregation Inhibitors
Placebos
Heparin
Ischemia
Fibrinogen Receptors
Pharmaceutical Preparations
Ambulatory Electrocardiography
eptifibatide
Platelet Aggregation
Blood Platelets
Hemorrhage

Keywords

  • angina
  • integrins
  • ischemia
  • platelets

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Schulman, S. P., Goldschmidt-Clermont, P., Topol, E. J., Califf, R. M., Navetta, F. I., Willerson, J. T., ... 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.

Effects of Integrelin, a platelet glycoprotein IIb/IIIa receptor antagonist, in unstable angina : A randomized multicenter trial. / Schulman, Steven P.; Goldschmidt-Clermont, Pascal; Topol, Eric J.; Califf, Robert M.; Navetta, Frank I.; Willerson, James T.; Chandra, Nisha C.; Guerci, Alan D.; Ferguson, James J.; Harrington, Roben A.; Lincoff, A. Michael; Yakubov, Steven J.; Bray, Paul F.; Bahr, Raymond D.; Wolfe, Christopher L.; Yock, Paul G.; Vernon Anderson, H.; Nygaard, Thomas W.; Mason, Steven J.; Effron, Mark B.; Fatterpacker, Anil; Raskin, Stephen; Smith, Jack; Brashears, Lori; Gottdiener, Patricia; Du Mee, Charles; Kitt, Michael M.; Gerstenblith, Gary.

In: Circulation, Vol. 94, No. 9, 07.11.1996, p. 2083-2089.

Research output: Contribution to journalArticle

Schulman, SP, Goldschmidt-Clermont, P, Topol, EJ, Califf, RM, Navetta, FI, Willerson, JT, Chandra, NC, Guerci, AD, Ferguson, JJ, Harrington, RA, Lincoff, AM, Yakubov, SJ, Bray, PF, Bahr, RD, Wolfe, CL, Yock, PG, Vernon Anderson, H, Nygaard, TW, Mason, SJ, Effron, MB, Fatterpacker, A, Raskin, S, Smith, J, Brashears, L, Gottdiener, P, Du Mee, C, Kitt, MM & Gerstenblith, G 1996, 'Effects of Integrelin, a platelet glycoprotein IIb/IIIa receptor antagonist, in unstable angina: A randomized multicenter trial', Circulation, vol. 94, no. 9, pp. 2083-2089.
Schulman SP, Goldschmidt-Clermont P, Topol EJ, Califf RM, Navetta FI, Willerson JT et al. Effects of Integrelin, a platelet glycoprotein IIb/IIIa receptor antagonist, in unstable angina: A randomized multicenter trial. Circulation. 1996 Nov 7;94(9):2083-2089.
Schulman, Steven P. ; Goldschmidt-Clermont, Pascal ; Topol, Eric J. ; Califf, Robert M. ; Navetta, Frank I. ; Willerson, James T. ; Chandra, Nisha C. ; Guerci, Alan D. ; Ferguson, James J. ; Harrington, Roben A. ; Lincoff, A. Michael ; Yakubov, Steven J. ; Bray, Paul F. ; Bahr, Raymond D. ; Wolfe, Christopher L. ; Yock, Paul G. ; Vernon Anderson, H. ; Nygaard, Thomas W. ; Mason, Steven J. ; Effron, Mark B. ; Fatterpacker, Anil ; Raskin, Stephen ; Smith, Jack ; Brashears, Lori ; Gottdiener, Patricia ; Du Mee, Charles ; Kitt, Michael M. ; Gerstenblith, Gary. / Effects of Integrelin, a platelet glycoprotein IIb/IIIa receptor antagonist, in unstable angina : A randomized multicenter trial. In: Circulation. 1996 ; Vol. 94, No. 9. pp. 2083-2089.
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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.",
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author = "Schulman, {Steven P.} and Pascal Goldschmidt-Clermont and Topol, {Eric J.} and Califf, {Robert M.} and Navetta, {Frank I.} and Willerson, {James T.} and Chandra, {Nisha C.} and Guerci, {Alan D.} and Ferguson, {James J.} and Harrington, {Roben A.} and Lincoff, {A. Michael} and Yakubov, {Steven J.} and Bray, {Paul F.} and Bahr, {Raymond D.} and Wolfe, {Christopher L.} and Yock, {Paul G.} and {Vernon Anderson}, H. and Nygaard, {Thomas W.} and Mason, {Steven J.} and Effron, {Mark B.} and Anil Fatterpacker and Stephen Raskin and Jack Smith and Lori Brashears and Patricia Gottdiener and {Du Mee}, Charles and Kitt, {Michael M.} and Gary Gerstenblith",
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T1 - Effects of Integrelin, a platelet glycoprotein IIb/IIIa receptor antagonist, in unstable angina

T2 - A randomized multicenter trial

AU - Schulman, Steven P.

AU - Goldschmidt-Clermont, Pascal

AU - Topol, Eric J.

AU - Califf, Robert M.

AU - Navetta, Frank I.

AU - Willerson, James T.

AU - Chandra, Nisha C.

AU - Guerci, Alan D.

AU - Ferguson, James J.

AU - Harrington, Roben A.

AU - Lincoff, A. Michael

AU - Yakubov, Steven J.

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AU - Bahr, Raymond D.

AU - Wolfe, Christopher L.

AU - Yock, Paul G.

AU - Vernon Anderson, H.

AU - Nygaard, Thomas W.

AU - Mason, Steven J.

AU - Effron, Mark B.

AU - Fatterpacker, Anil

AU - Raskin, Stephen

AU - Smith, Jack

AU - Brashears, Lori

AU - Gottdiener, Patricia

AU - Du Mee, Charles

AU - Kitt, Michael M.

AU - Gerstenblith, Gary

PY - 1996/11/7

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N2 - 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.

AB - 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.

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