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Platelet membrane receptor glycoprotein IIb/IIIa antagonism in unstable angina. The Canadian Lamifiban Study.
Circulation. 1996 Sep 01; 94(5):899-905.Circ

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 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+Show Affiliations

Department of Medicine, Montreal Heart Institute, Quebec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

8790023

Citation

Théroux, P, et al. "Platelet Membrane Receptor Glycoprotein IIb/IIIa Antagonism in Unstable Angina. the Canadian Lamifiban Study." Circulation, vol. 94, no. 5, 1996, pp. 899-905.
Théroux P, Kouz S, Roy L, et al. Platelet membrane receptor glycoprotein IIb/IIIa antagonism in unstable angina. The Canadian Lamifiban Study. Circulation. 1996;94(5):899-905.
Théroux, P., Kouz, S., Roy, L., Knudtson, M. L., Diodati, J. G., Marquis, J. F., Nasmith, J., Fung, A. Y., Boudreault, J. R., Delage, F., Dupuis, R., Kells, C., Bokslag, M., Steiner, B., & Rapold, H. J. (1996). Platelet membrane receptor glycoprotein IIb/IIIa antagonism in unstable angina. The Canadian Lamifiban Study. Circulation, 94(5), 899-905.
Théroux P, et al. Platelet Membrane Receptor Glycoprotein IIb/IIIa Antagonism in Unstable Angina. the Canadian Lamifiban Study. Circulation. 1996 Sep 1;94(5):899-905. PubMed PMID: 8790023.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Platelet membrane receptor glycoprotein IIb/IIIa antagonism in unstable angina. The Canadian Lamifiban Study. AU - Théroux,P, AU - Kouz,S, AU - Roy,L, AU - Knudtson,M L, AU - Diodati,J G, AU - Marquis,J F, AU - Nasmith,J, AU - Fung,A Y, AU - Boudreault,J R, AU - Delage,F, AU - Dupuis,R, AU - Kells,C, AU - Bokslag,M, AU - Steiner,B, AU - Rapold,H J, PY - 1996/9/1/pubmed PY - 1996/9/1/medline PY - 1996/9/1/entrez SP - 899 EP - 905 JF - Circulation JO - Circulation VL - 94 IS - 5 N2 - 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 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. SN - 0009-7322 UR - https://www.unboundmedicine.com/medline/citation/8790023/Platelet_membrane_receptor_glycoprotein_IIb/IIIa_antagonism_in_unstable_angina__The_Canadian_Lamifiban_Study_ DB - PRIME DP - Unbound Medicine ER -