Rationale for intracoronary administration of abciximab.
The present review aims to describe the pharmacological aspects as well as the available clinical data supporting the choice of intracoronary route of administration for abciximab, an antiplatelet drug used in patients with acute coronary syndromes undergoing percutaneous coronary interventions (PCI). Abciximab is a glycoprotein (GP) IIb/IIIa receptor antagonist which determines a potent inhibition of platelet aggregation and thrombus formation. These properties seem to prevent not only thrombus formation but also to promote (at higher drug concentration) lysis of fresh thrombus. Moreover, differently from the other GP IIb/IIIa inhibitors, abciximab also binds to the vitronectin receptor on endothelial, smooth muscle, and inflammatory cells and to an activated conformation of the aMb2 receptor on leukocytes. Such cross-reactivity raises the possibility that clinical benefits derived from its use may not be exclusively due to its anti-thrombotic effect, but may also be related to the suppression of inflammatory pathways involving platelets, white blood cells, and the vascular endothelium. On such basis, the local administration of abciximab at the site of coronary thrombosis may enhance, by increasing its local concentration, the binding to both platelet and endothelium receptors. The results of several angiographic studies assessing the effect of intracoronary abciximab administration support on clinical grounds its adoption in patients with fresh coronary thrombosis. Indeed, better post-angioplasty coronary flow, greater degree of myocardial salvage and a better left ventricular function recovery have been achieved as compared to the intravenous, systemic, administration of drug's bolus. Condensed Abstract Several studies have highlighted the benefits of abciximab, a potent antiplatelet agent, in patients with acute coronary syndromes undergoing percutaneous coronary interventions. Moreover, differently from the other glycoprotein IIb/IIIa receptor antagonists, abciximab also has non-IIb/IIIa-related properties raising the possibility that clinical benefits derived from its use may not be exclusively due to its anti-thrombotic effect, but may also be related to the suppression of inflammatory pathways. Several angiographic studies in patients with fresh coronary thrombosis and recent clinical studies in patients with acute coronary syndromes undergoing mechanical revascularization support the hypothesis that local administration of abciximab at the site of the culprit coronary artery may facilitate both the de-thrombotic and the non-GP IIb/IIIa-dependent properties of the drug. On such basis, the present review aims to describe the pharmacological aspects as well as the available clinical data supporting the choice of intracoronary route of administration for abciximab.
Romagnoli
Enrico
E
Department of cardiovascular disease, Catholic University, Campobasso, Italy. enromagnolimd@hotmail.com
Burzotta
Francesco
F
Trani
Carlo
C
Biondi-Zoccai
Giuseppe G L
GG
Giannico
Floriana
F
Crea
Filippo
F
D000077284:Abciximab; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology*; D003328:Coronary Thrombosis / Q000517:prevention & control; D004333:Drug Administration Routes; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage* / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology*; D016032:Randomized Controlled Trials as Topic
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D000077284:Abciximab