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(Circulation. 1996;94:899-905.)
© 1996 American Heart Association, Inc.
Articles |
Platelet Membrane Receptor Glycoprotein IIb/IIIa Antagonism in Unstable Angina
The Canadian Lamifiban Study
the Department of Medicine, Montreal Heart Institute and University of Montreal (Quebec, Canada), and Hoffman La Roche, Basel, Switzerland (M.B., B.S., H.J.R.).
Correspondence to Pierre Theroux, MD, Montreal Heart Institute, 5000 Belanger St, Montreal, Quebec, H1T 1C8, Canada.
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.
Key Words: platelets • angina • lamifiban • heparin • coronary disease
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