EFFECTS OF INTEGRELIN, A PLATELET GLYCOPROTEIN IIB IIIA RECEPTOR ANTAGONIST, IN UNSTABLE ANGINA - A RANDOMIZED MULTICENTER TRIAL/

Background Although aspirin is beneficial in patients with unstable an gina, it is a relatively weak inhibitor of platelet aggregation. The e ffect of Integrelin, which inhibits the platelet fibrinogen receptor g lycoprotein (GP) IIb/IIIa, on the frequency and duration of Holter isc hemia was evaluated in 227 patients with unstable angina. Methods and Results Patients received intravenous heparin and standard anti-ischem ic therapy and were randomized to receive oral aspirin and placebo Int egrelin; placebo aspirin and low-dose Integrelin, 45 mu g/kg bolus fol lowed by a 0.5-mu g . kg(-1). min(-1) continuous infusion; or placebo aspirin and high-dose Integrelin, 90 mu g/kg bolus followed by a 1.0-m u g . kg(-1). min(-1) constant infusion. Study drug was continued for 24 to 72 hours, and Holter monitoring was performed. Patients randomiz ed to high dose Integrelin experienced 0.24+/-0.11 ischemic episodes ( mean+/-SEM) on Holler lasting 8.41+/-5.29 minutes over 24 hours of stu dy 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. C onclusions Intravenous Integrelin is well tolerated, is a potent rever sible inhibitor of platelet aggregation, and added to full-dose hepari n reduces the number and duration of Holter ischemic events in patient s with unstable angina compared with aspirin.