PLATELET MEMBRANE-RECEPTOR GLYCOPROTEIN-IIB IIIA ANTAGONISM IN UNSTABLE ANGINA - THE CANADIAN LAMIFIBAN STUDY/

Background Ligand binding to the platelet membrane receptor glycoprote in (GP) IIb/IIIa, the final and obligatory step to platelet aggregatio n, can now be inhibited by pharmacological agents. This study was desi gned to evaluate the potential of lamifiban, a novel nonpeptide antago nist of GP IIb/IIIa, for the management of unstable angina. Methods an d Results In a prospective, dose-ranging, double-blind study, 365 pati ents with unstable angina were randomized to an infusion of 1, 2, 4, o r 5 mu g/min of lamifiban or of placebo. Treatment was administered fo r 72 to 120 hours. Outcome events were measured during the infusion pe riod and after 1 month. Concomitant aspirin was administered to all pa tients and heparin to 28% of patients. Lamifiban, all doses combined, reduced the risk of death, nonfatal myocardial infarction, or the need for an urgent revascularization during the infusion period from 8.1% to 3.3% (P=.04). The rates were 2.5%, 4.9%, 3.3%, and 2.4% with increa sing doses. At 1 month, death or nonfatal infarction occurred in 8.1% of patients with placebo and in 2.5% of patients with the two high dos es (P=.03). The highest dose of lamifiban additionally prevented the n eed for an urgent intervention. Lamifiban hose-dependently inhibited p latelet aggregation. Bleeding times were significantly prolonged with platelet inhibition of >80%. Major (but neither life-threatening nor i ntracranial) bleedings occurred in 0.8% of patients with placebo and 2 .9% with lamifiban. Conclusions The nonpeptide GP IIb/IIIa antagonist lamifiban protected patients with unstable angina from severe ischemic events during a 3- to 5-day infusion and reduced the incidence of dea th and infarction at 1 month, suggesting considerable promise for this new therapeutic approach.