Glycoprotein IIb/IIIa antagonists in acute coronary syndromes: where are we now?
Vascular inflammation, coronary constriction, and thrombus formation are central to all acute coronary syndromes (ACSs). Adhesion and aggregation of activated platelets, initially described during thrombosis, now appear pivotal to all three processes. Several platelet adhesion receptors participate but the integrin glycoprotein (GP) IIb/IIIa occupies a critical role. GPIIb/IIIa antagonists used as an adjunct to percutaneous coronary intervention show clear benefit. However in the setting of ACS results have been disappointing. Indeed, trials of oral GPIIb/IIIa antagonists in patients with ACS were associated with increased mortality. Difficulties with drug dosing and variable pharmacodynamics may contribute to suboptimal receptor occupancy, incomplete inhibition of platelet aggregation, paradoxical partial agonist activity, and proinflammatory effects. Moreover, variable responses of patients to GPIIb/IIIa antagonists may reflect population heterogeneity.
Maree
Andrew
A
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland.
Fitzgerald
Desmond J
DJ
D000208:Acute Disease; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000502:physiology*; D013577:Syndrome
D019039:Platelet Glycoprotein GPIIb-IIIa Complex