FIRST CHRONIC PLATELET GLYCOPROTEIN IIB IIIA INTEGRIN BLOCKADE - A RANDOMIZED, PLACEBO-CONTROLLED PILOT-STUDY OF XEMILOFIBAN IN UNSTABLE ANGINA WITH PERCUTANEOUS CORONARY INTERVENTIONS/

Background Clinical studies have demonstrated the efficacy of intraven ous administration of agents that block platelet glycoprotein IIb/IIa receptors in the setting of percutaneous coronary revascularization. A lthough the optimal duration of treatment has not been determined, mon prolonged receptor blockade has been associated with increased effica cy. Orally active glycoprotein IIb/IIIa receptor antagonists may be ad vantageous and required for chronic therapy. Methods and Results Thirt y patients with unstable angina who were undergoing percutaneous coron ary interventions were randomized to placebo or Xemilofiban 35 mg oral ly before and 20 to 25 mg TLD for 30 days after angioplasty. Bleeding events, platelet aggregation, and pharmacokinetic and hematologic para meters were assessed during hospitalization and at 2 and 4 weeks after drug initiation. Xemilofiban produced a rapid, sustained, marked inhi bition of platelet aggregation, ADP-induced platelet aggregation at 2 hours after the initial dose at 2 and 4 weeks was 15%, 8%, and 11% in the Xemilofiban group compared with 80%, 68%, and 69% in the placebo g roup, Among 20 patients randomized to Xemilofiban there was 1 death af ter emergency coronary bypass surgery complicated by severe bleeding d iathesis, and 3 patients had major bleeding events. Patients on Xemilo fiban for 30 days reported episodes of mild mucocutaneous bleeding. Co nclusions Xemilofiban, an orally active glycoprotein IIb/IIIa receptor inhibitor, produced rapid, sustained, extensive inhibition of platele t aggregation for a period of up to 30 days. At the dose initially tes ted, however, acute major bleeding and mucocutaneous bleeding during c hronic administration were encountered.