title: Platelet membrane receptor glycoprotein IIb/IIIa antagonism in unstable angina. The Canadian Lamifiban Study.
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.
  
  
  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 micrograms/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.
authors.affiliation: Department of Medicine, Montreal Heart Institute, Quebec, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Théroux
authors.forename: S
authors.initials: S
authors.lastname: Kouz
authors.forename: L
authors.initials: L
authors.lastname: Roy
authors.forename: M L
authors.initials: ML
authors.lastname: Knudtson
authors.forename: J G
authors.initials: JG
authors.lastname: Diodati
authors.forename: J F
authors.initials: JF
authors.lastname: Marquis
authors.forename: J
authors.initials: J
authors.lastname: Nasmith
authors.forename: A Y
authors.initials: AY
authors.lastname: Fung
authors.forename: J R
authors.initials: JR
authors.lastname: Boudreault
authors.forename: F
authors.initials: F
authors.lastname: Delage
authors.forename: R
authors.initials: R
authors.lastname: Dupuis
authors.forename: C
authors.initials: C
authors.lastname: Kells
authors.forename: M
authors.initials: M
authors.lastname: Bokslag
authors.forename: B
authors.initials: B
authors.lastname: Steiner
authors.forename: H J
authors.initials: HJ
authors.lastname: Rapold
mesh_terms: D000085:Acetates / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000789:Angina, Unstable / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000627:therapeutic use
chemical_list: D000085:Acetates; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; C084062:lamifiban