Platelet Membrane Receptor Glycoprotein IIb/IIIa Antagonism in Unstable Angina

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Abstract
Background Ligand binding to the platelet membrane receptor glycoprotein (GP) IIb/IIIa, the final and obligatory step to platelet aggregation, can now be inhibited by pharmacological agents. This study was designed to evaluate the potential of lamifiban, a novel nonpeptide antagonist of GP IIb/IIIa, for the management of unstable angina. Methods and Results In a prospective, dose-ranging, double-blind study, 365 patients with unstable angina were randomized to an infusion of 1, 2, 4, or 5 μg/min of lamifiban or of placebo. Treatment was administered for 72 to 120 hours. Outcome events were measured during the infusion period and after 1 month. Concomitant aspirin was administered to all patients 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 increasing 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 doses ( P =.03). The highest dose of lamifiban additionally prevented the need for an urgent intervention. Lamifiban dose-dependently inhibited platelet aggregation. Bleeding times were significantly prolonged with platelet inhibition of >80%. Major (but neither life-threatening nor intracranial) 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 death and infarction at 1 month, suggesting considerable promise for this new therapeutic approach.