Safety issues surrounding use of platelet GP IIb/IIIa antagonists: Reversibility and readministration

The platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonists abciximab, eptifibatide, and tirofiban have been shown to be safe and effective in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. Consequently, the use of these drugs is becoming increasingly common. However, issues regarding the ability to reverse their effects remain, particularly in the setting of emergency surgery. The short-acting agents eptifibatide and tirofiban are characterized by less avid binding, significant plasma reservoirs of unbound drug, rapid decay of receptor occupancy and relatively rapid clearance in the presence of intact renal/hepatic mechnisms. The avid-binding abciximab is characterized by a shorter plasma half-life, relative absence of unbound drug, a long platelet-bound half-life, and a relatively prolonged duration of effect mediated by the redistribution and equilibration of drug molecules among circulating platelets at progressively lower degrees of receptor occupancy. Six to 12 h after discontinuation of abciximab, receptor occupancy has dropped below the threshold for maximal inhibition of aggregation, resulting in partial restoration of platelet function and the degree of receptor occupancy gradually declining thereafter. These characteristics (specifically, lack of plasma reservoir) suggest that the platelet inhibitory effects of abciximab may be reversed by platelet transfusion so as to increase the available platelet population and decrease the degree of receptor occupancy. There also has been concern that the readministration of abciximab might be associated with allergic responses, an increased incidence and severity of thrombocytopaenia, and reduced effectiveness, because of the re-exposure to a foreign antigen. Data from a phase IV registry of abciximab readministration, corroborated by independent reports, have indicated no increase in adverse effects or decrease in effectiveness in patients receiving subsequent doses of the agent, irrespective of the presence of an antibody response to the first administration of abciximab.

Duke Scholars

Author James Enlou Tcheng Medicine, Cardiology