Intravenous glycoprotein IIb/IIIa antagonists: their benefits, problems and future developments.
The intravenous Glycoprotein (GP) IIb/IIIa antagonists are potent antiplatelet agents that are particularly effective in patients who undergo percutaneous coronary intervention (PCI). Questions remain about their benefit in the setting of primary PCI, as well as in patients with acute coronary syndromes who do not undergo PCI. The dosing of these drugs is critical to their efficacy and for some agents may not yet be optimized. Differences in the level of platelet inhibition achieved with previous and current dosing strategies of these agents are discussed. In addition, the pharmacology of GPIIb/IIIa antagonists is more complex than initially appreciated. These drugs appear to have partial agonist properties and as a result may be prothrombotic at lower doses. Recent evidence also suggests that at least some of the GPIIb/IIIa antagonists may have anti-inflammatory as well as anti-thrombotic activity. Future research should clarify these issues. Because of the observed inter-individual variation in the response to GPIIb/IIIa antagonists, future trials of these agents should also look at individual tailoring of the dose to an optimum level of platelet inhibition. No definite clinical predictors of this inter-individual variation have been identified, but the Pl(A) polymorphism in GPIIIa appears to be associated with an adverse response to treatment with the oral GPIIb/IIIa antagonists in particular.
Curtin
Ronan
R
Dept. of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland. rcurtin@rcsi.ie
D000818:Animals; D002986:Clinical Trials as Topic / Q000639:trends; D003327:Coronary Disease / Q000188:drug therapy / Q000378:metabolism; D004334:Drug Administration Schedule; D006801:Humans; D007275:Injections, Intravenous; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism
D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex