title: Impact of P2Y12-ADP receptor polymorphism on the efficacy of clopidogrel dose-adjustment according to platelet reactivity monitoring in coronary artery disease patients.
abstract: BACKGROUND
  High on-treatment platelet reactivity (HTPR) after clopidogrel loading dose (LD) is associated with a high risk of thrombotic events after percutaneous coronary intervention(PCI). We have demonstrated that HTPR could be overcome in the majority of cases using LD adjustment resulting in an improved clinical outcome. However this strategy failed in nearly 10% of patients with HTPR. We aimed to determine if P2Y12-ADP receptor polymorphisms were associated with failed dose adjustment.
  
  
  METHODS
  Forty-three patients undergoing PCI were included in this prospective study. A VASP index >or=50% after a 600 mg LD of clopidogrel defined HTPR. Dose adjustment was performed according to PR monitoring to reach a VASP index <50%. Genetic polymorphism of the P2Y12-ADP receptor was determined by direct sequencing.
  
  
  RESULTS
  Patients with successful dose-adjustment (SDA) (n=33) and failed (FDA) (n=10) dose-adjustment groups were compared. The 2 groups were similar in terms of cardiovascular risk factors including diabetes mellitus (SDA vs FDA: 42 vs 20%; p=0.3). The prevalence of the H2 allele of the P2Y12-ADP receptor was also similar between the 2 groups (p=0.3). The H2 allele was found in 6 patients which are all included in the SDA group. After the first 600 mg loading dose of clopidogrel, patients carrying at least one H2 allele had similar VASP index compared to those carrying two copies of the wild type allele (H1) (SDA vs FDA: 44.9+/-14.9 vs 43.5+/-10%; p=0.8).
  
  
  CONCLUSIONS
  The present study suggests that the H2 allele of the P2Y12-ADP receptor is not involved in clopidogrel failed dose adjustment according to platelet reactivity monitoring.
authors.affiliation: Département de cardiologie, Hôpital Universitaire Nord, faculté de médecine, Marseille, France. laurentbonello@yahoo.fr
authors.forename: Laurent
authors.initials: L
authors.lastname: Bonello
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bonello-Palot
authors.forename: Sébastien
authors.initials: S
authors.lastname: Armero
authors.forename: Caroline
authors.initials: C
authors.lastname: Bonello
authors.forename: Omar Ait
authors.initials: OA
authors.lastname: Mokhtar
authors.forename: Stéphane
authors.initials: S
authors.lastname: Arques
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.forename: Laurence
authors.initials: L
authors.lastname: Camoin-Jau
authors.forename: Franck
authors.initials: F
authors.lastname: Paganelli
mesh_terms: D000368:Aged; D000483:Alleles; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000235:genetics; D003327:Coronary Disease / Q000188:drug therapy / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics / Q000494:pharmacology; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018048:Receptors, Purinergic P2 / Q000235:genetics* / Q000627:therapeutic use; D012917:Social Adjustment; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D018048:Receptors, Purinergic P2; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D013988:Ticlopidine