Pharmacodynamic Profile of Short-term Abciximab Treatment Demonstrates Prolonged Platelet Inhibition With Gradual Recovery From GP IIb/IIIa Receptor Blockade

Abstract

These results are consistent with continuous reequilibration of abciximab among circulating platelets and may explain the gradual recovery of platelet function and long-term prevention of ischemic complications by abciximab after coronary intervention.

Intracoronary Compared With Intravenous Bolus Abciximab Application in Patients With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

“…However, even in situations with restitution of normal flow and perfusion in the infarct-related artery, intracoronary abciximab bolus administration will result in very high local concentrations, which might be much higher than the usual intravenous application mode that reduces platelet aggregation to Ͻ20% within 10 minutes. 28 Another potential mechanism of high local concentrations might be related to the antiinflammatory properties of abciximab. 7 These clinical considerations are supported by experimental data showing a dose-dependent platelet disaggregation.…”

Platelet Glycoprotein IIb/IIIa Inhibitors

“…Flow cytometry shows that histograms representing bound drug within the total platelet population remain homogeneous while decreasing in intensity. 5 EPIC 6 and EPILOG 7 trials, among others, showed a beneficial effect of sustained blockade of the GPIIb-IIIa receptor by abciximab in patients undergoing high-risk percutaneous transluminal coronary angioplasty (PTCA) or directional coronary atherectomy. The effect was defined in EPIC as a 35% relative risk reduction of death, myocardial infarction, or urgent revascularization within 30 days.…”

“…7,9 The occasional need for emergency coronary bypass surgery is helped by the rapid clearance of abciximab from plasma, and platelet transfusion will provide functional platelets, lower the free plasma levels of the drug further, and promote the antibody exchange that has been suggested to occur between circulating platelets. 5 Abciximab also substantially improves the safety of coronary stenting, now used in Ͼ60% of percutaneous revascularization procedures in the United States. 10 Stenting can itself promote GPIIb-IIIa complex activation and predispose to coronary thrombus formation.…”

“…4,9,26 Among the other factors that may influence the recovery rate after anti-GPIIb-IIIa therapy are (1) variations in the plasma levels of free drug, (2) the rate at which surface-bound drug dissociates from circulating platelets, 5 and (3) the extent to which GPIIb-IIIa receptors are exchanged between surface and internal pools. 28 Therefore, it is reasonable to suggest that biological surveillance, with testing of platelet function and flexibility with regard both to the doses used and the duration of therapy, may help to improve the success rate with anti-GPIIb-IIIa inhibitors in acute situations.…”

Mortality Reduction with Administration of Abciximab during Primary PCI is Confined to STEMI Patients with Complex Lesions

“…Since the waiting period between diagnosis and treatment has shortened the time for abciximab to work is correspondingly short. Since the action of abciximab relies mainly on inhibition of thrombus formation and propagation [20][21][22], and possibly also exhibits some degree of thrombus disaggregation [23][24][25], only in the cases were thrombus is actually present, one can expect an effect of abciximab. If thrombus is not present the effect will be absent and the treatment might even be harmful, since the side effects of abciximab, that is bleeding, will outweigh the potential benefit.…”