(Circulation. 1996;94:2083-2089.)
© 1996 American Heart Association, Inc.
Articles |
Effects of Integrelin, a Platelet Glycoprotein IIb/IIIa Receptor Antagonist, in Unstable Angina
A Randomized Multicenter Trial
the Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, Md; Cleveland (Ohio) Clinic Foundation; Duke University Medical Center, Durham, NC; Mother Frances Hospital, Tyler, Tex; University of Texas, Houston; St Frances Hospital, Roslyn, NY; Texas Heart Institute, Houston; Riverside Methodist Hospital, Columbus, Ohio; St Agnes Hospital, Baltimore, Md; Moffitt Hospital, University of California, San Francisco; Lynchburg (Va) General Hospital; Franklin Square Hospital, Baltimore, Md; Alameda (Calif) Hospital; St Vincent's Hospital, Erie, Pa; Biometric Research Institute, Arlington, Va; and COR Therapeutics, San Francisco, Calif.
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.
Key Words: integrins • angina • platelets • ischemia
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