The glycoprotein (Gp) IIb/IIIa (alpha-Iib beta-3) is expressed on the platelet surface where it exists in an equilibrium between a resting state, unable to bind adhesive proteins and an active (ligand binding- competent) state. Following platelet activation, the Gp IIB/IIIaa complex undergoes a conformational change (inside-out signaling), leading to binding of divalent fibrinogen with consequent formation of fibrinogen bridges between platelets and, ultimately, to platelet aggregation and thrombus formation. Fibrinogen binding to activated platelets is the final common step in platelet aggregation, regardless of the initiating event. In the last ten years several compounds, monoclonal antibodies and synthetic peptidic and nonpeptidic molecules, have been designed to antagonize the binding of fibrinogen to the platelet complex. Several clinical trials have investigated the efficacy and safety of these compounds in various clinical conditions. Orbofiban is an orally active antagonist of the IIb/IIIa complex. The present study will evaluate the safety and pharmacodynamic response of 4 doses (30 mg bid, 40 mg bid, 50 mg bid and 50 mg qd) of Orfbofiban plus aspirin compared to placebo plus aspirin in patients with recent (<96 hours) acute coronary artery syndromes. Orbofin ban will be given for 30 days. Platelet aggregation and plasma levels of orbofiban will be assessed on day 2, 14 and 28. A total of 150 patients will be enrolled in 15 centers.
Showing the most recent 10 out of 423 publications
