title: IIb's are not IIb's.
abstract: Platelet glycoprotein (GP) IIb/IIIa receptor blockade improves clinical outcomes after percutaneous coronary intervention (PCI) and for patients who present with non-ST-segment elevation acute coronary syndromes. Although this class of therapeutic agents has been defined by a common affinity for the platelet GP IIb/IIIa receptor, the 3 currently available agents differ markedly in pharmacodynamic and pharmacokinetic profile as well as receptor affinity. Differential (separate) binding sites on the GP IIb/IIIa receptor explain the observation that abciximab binding to platelets is not influenced by either tirofiban or eptifibatide. Abciximab (ReoPro, chimeric 7E3 Fab) is a low K(d) (high affinity) agent with a very short plasma t(1/2) and a prolonged duration of action at the platelet target receptor. Eptifibatide and tirofiban are high K(d) (low affinity) agents with a relatively long plasma t(1/2) and short duration of action at the platelet target receptor. These pharmacodynamic differences underlie the phenomena of gradual redistribution in abciximab binding and smooth tapering of abciximab antiplatelet effect after discontinuation of therapy. Furthermore, abciximab demonstrates affinity for both the CD11b/18 (alpha(m)beta(2) or MAC 1) and alpha(V)beta(3) (vitronectin) receptors. Although a survival advantage in favor of abciximab has been observed after PCI in both randomized controlled trials and high-volume clinical practice, no survival benefit has been observed to date after eptifibatide or tirofiban therapy for PCI. The mechanism of survival advantage after abciximab therapy has not been defined but may be distinct from the degree of platelet GP IIb/IIIa receptor inhibition during the duration of intravenous treatment. Although this important new "class" of therapeutic agent was simplistically defined by a common affinity for the GP IIb/IIIa receptor, this solitary unifying attribute may not define agent-specific benefit.
authors.affiliation: The Carl and Edyth Lindner Center for Research and Education, Cincinnati, Ohio, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Kereiakes
authors.forename: J P
authors.initials: JP
authors.lastname: Runyon
authors.forename: T M
authors.initials: TM
authors.lastname: Broderick
authors.forename: T M
authors.initials: TM
authors.lastname: Shimshak
mesh_terms: D000077284:Abciximab; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000077542:Eptifibatide; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000188:drug therapy*; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D016032:Randomized Controlled Trials as Topic; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019096:Vitronectin
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019096:Vitronectin; D014443:Tyrosine; D000077466:Tirofiban; D000077542:Eptifibatide; D000077284:Abciximab