title: PlA(1)/PlA(2) polymorphism does not influence response to Gp IIb-IIIa inhibitors in patients undergoing coronary angioplasty.
abstract: Glycoprotein IIb-IIIa (Gp IIb-IIIa), a fibrinogen receptor located on platelet surface, is a key point in the pathway leading to platelet aggregation. Therefore, great interest has emerged in the last decades on its pharmacological block, both by irreversible binding of abciximab or by competitive small molecules (tirofiban and eptifibatide). Gp IIb-IIIa inhibitors, in fact have demonstrated to provide benefits in clinical outcome among patients with acute myocardial infarction and in complex elective percutaneous coronary intervention (PCI) procedures. Still unclear is whether the genetic Leu 33Pro substitution in Gp IIIa may affect the extent of platelet aggregation inhibition by these drugs. Therefore, the aim was to evaluate whether this polymorphism (PlA) may influence inhibition of platelet aggregation after Gp IIb-IIIa administration in patients undergoing coronary angioplasty. We analyzed 80 patients undergoing nonurgent coronary revascularization and receiving Gp IIb-IIIa inhibitors (bolus and endovenous infusion; 40 patients with Abciximab and 40 patients with eptifibatide or tirofiban). The aggregation tests were performed at baseline and after 10 min, 1 h and 4 h, through multiplate impedance aggregometry. The PlA polymorphic variant was found in 26 patients (32.5%). The PlA carriers did not differ significantly from wild-type subjects for main clinical and angiographic features, except for in-stent restenosis that was more frequent among PlA carriers (P = 0.003). Therapy and aggregation values at baseline were similar in the two groups. The Leu33Pro substitution did not influence platelet response after Gp IIb-IIIa administration, which was confirmed for both abciximab and small molecules. This study showed that Leu33Pro polymorphism of Gp IIIa does not affect the extent of inhibition of platelet aggregation by Gp IIb-IIIa inhibitors.
authors: Division of Cardiology, Azienda Ospedaliera-Universitaria Maggiore della Carità, Eastern Piedmont University, Novara, Italy.
authors: Monica
authors: M
authors: Verdoia
authors: Patrizia
authors: P
authors: Pergolini
authors: Cyril
authors: C
authors: Camaro
authors: Maria
authors: M
authors: Restifo
authors: Roberta
authors: R
authors: Rolla
authors: Alon
authors: A
authors: Schaffer
authors: Gabriella
authors: G
authors: Di Giovine
authors: Paolo
authors: P
authors: Marino
authors: Giorgio
authors: G
authors: Bellomo
authors: Harry
authors: H
authors: Suryapranata
authors: Giuseppe
authors: G
authors: De Luca
mesh_terms: D000077284:Abciximab; D000368:Aged; D019943:Amino Acid Substitution; D015906:Angioplasty, Balloon, Coronary; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004334:Drug Administration Schedule; D000077542:Eptifibatide; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D007930:Leucine / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D010455:Peptides / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics / Q000378:metabolism; D000077466:Tirofiban; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D011392:Proline; D000077466:Tirofiban; D007930:Leucine; D000077542:Eptifibatide; D000077284:Abciximab