Abstract
Adjunctive blockade of platelet glycoprotein (GP) IIb/IIIa during percutaneous coronary intervention (PCI) or in patients who present with acute coronary syndromes has been effective in reducing platelet-mediated adverse ischemic clinical outcomes (1–6). Although this class of therapeutic agents has been defined by a shared common affinity for the GPIIb/IIIa integrin receptor, the three agents that are currently US Food and Drug Administration (FDA)-approved differ markedly in pharmacodynamic and pharmacokinetic profile as well as receptor affinity. Separate specific and distinct binding sites on the GPIIb/IIIa receptor complex have been delineated for abciximab and the small-molecule GPIIb/IIIa inhibitors (eptifibatide, tirofiban) by means of differential displacement of site-specific monoclonal antibodies, including MAb1 (LYP18) and MAb2 (4F8) (7). Abciximab has been demonstrated to bind a specific complex recognition site, whereas the smallmolecule antagonists bind directly to the RGD component on the fβ3 subunit of the receptor. Furthermore, abciximab is unique by demonstrating cross-affinity for additional integrin receptors, αvβ3 (vitronectin) (8–10), and CD 1 lb/1 8 (Mac 1) (11,12), which are found predominantly on white blood cells, smooth muscle cells, and endothelial cells. These additional integrin receptors modulate multiple functions distinct from platelet aggregation and could confer differential clinical benefit for abciximab in addition to its plateletinhibitory effects.