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

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 ischemic therapy and were randomized to receive oral aspirin and placebo Integrelin; placebo aspirin and low-dose Integrelin. 45 micrograms/kg bolus followed by a 0.5 microgram.kg-1. min-1 continuous infusion; or placebo aspirin and high-dose Integrelin, 90 micrograms/kg bolus followed by a 1.0-microgram.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.

• Authors: S P Schulman, P J Goldschmidt-Clermont, E J Topol, R M Califf, F I Navetta, J T Willerson, N C Chandra, A D Guerci, J J Ferguson, R A Harrington, A M Lincoff, S J Yakubov, P F Bray, R D Bahr, C L Wolfe, P G Yock, H V Anderson, T W Nygaard, S J Mason, M B Effron, A Fatterpacker, S Raskin, J Smith, L Brashears, P Gottdiener, C du Mee, M M Kitt, G Gerstenblith
• Journal: Circulation (Circulation) Vol. 94 Issue 9 Pg. 2083-9 (Nov 01 1996) ISSN: 0009-7322 [Print] United States
• PMID: 8901655 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Peptides
• Placebos
• Platelet Aggregation Inhibitors
• Platelet Glycoprotein GPIIb-IIIa Complex
• Heparin
• Eptifibatide
• Aspirin

Topics

• Adult
• Aged
• Aged, 80 and over
• Angina, Unstable (complications, drug therapy)
• Anticoagulants (pharmacology)
• Aspirin (pharmacology)
• Bleeding Time
• Dose-Response Relationship, Drug
• Double-Blind Method
• Electrocardiography, Ambulatory
• Eptifibatide
• Female
• Hemorrhage (chemically induced)
• Heparin (pharmacology)
• Humans
• Male
• Middle Aged
• Myocardial Infarction (etiology)
• Myocardial Ischemia (chemically induced, complications, drug therapy)
• Peptides (administration & dosage, adverse effects)
• Placebos
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (administration & dosage, adverse effects)
• Platelet Glycoprotein GPIIb-IIIa Complex (antagonists & inhibitors)
• Prospective Studies
• Sex Factors
• Substance Withdrawal Syndrome