title: CYP2C19*2 and *17 alleles have a significant impact on platelet response and bleeding risk in patients treated with prasugrel after acute coronary syndrome.
abstract: OBJECTIVE
  The present study was designed to assess the effect of genetic variants on chronic biological response to prasugrel and bleeding complications.
  
  
  BACKGROUND
  CYP2C19*2 loss-of-function allele and CYP2C19*17 gain-of-function allele have been linked with response to clopidogrel, but preliminary data did not show any significant influence of these alleles on prasugrel effect.
  
  
  METHODS
  A total of 213 patients undergoing successful coronary stenting for acute coronary syndrome and discharged with prasugrel 10 mg daily were included. Prasugrel response was assessed at 1 month with the platelet reactivity index (PRI) vasodilator-stimulated phosphoprotein (VASP) and high on-treatment platelet reactivity (HTPR) defined as PRI VASP > 50% and hyper-response as PRI VASP <75th percentile (PRI VASP < 17%). CYP2C19*2 and CYP2C19*17 genotyping were performed.
  
  
  RESULTS
  Carriers of loss-of-function *2 allele had significantly higher PRI VASP than noncarriers (33 ± 15% vs. 27 ± 14%, p = 0.03) and higher rate of HTPR (16% vs. 4%, p = 0.01). Conversely, carriers of *17 gain-of-function allele had significantly lower PRI VASP than noncarriers (25 ± 13% vs. 31 ± 15%, p = 0.03, p = 0.03), lower rate of HTPR (1% vs. 10%, p = 0.02), higher rate of hyper-response (34% vs. 21%, p = 0.02), and higher rate of bleeding complications than noncarriers: 23% versus 11%, (odds ratio [95% confidence interval]: 2.5 [1.2 to 5.4]; p = 0.02). No significant influence of genotypes on platelet reactivity assessed by adenosine diphosphate-induced platelet aggregation was observed.
  
  
  CONCLUSIONS
  The present study shows a significant influence of CYP2C19*2 and *17 alleles on response to chronic treatment by prasugrel 10 mg daily and occurrence of bleeding complications.
authors.affiliation: Dèpartement de Cardiologie, CHU Timone, Marseille, France. thomas.cuisset@ap-hm.fr
authors.forename: Thomas
authors.initials: T
authors.lastname: Cuisset
authors.forename: Marie
authors.initials: M
authors.lastname: Loosveld
authors.forename: Pierre Emmanuel
authors.initials: PE
authors.lastname: Morange
authors.forename: Jacques
authors.initials: J
authors.lastname: Quilici
authors.forename: Pierre Julien
authors.initials: PJ
authors.lastname: Moro
authors.forename: Noémie
authors.initials: N
authors.lastname: Saut
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Gaborit
authors.forename: Christel
authors.initials: C
authors.lastname: Castelli
authors.forename: Shirley
authors.initials: S
authors.lastname: Beguin
authors.forename: Charlotte
authors.initials: C
authors.lastname: Grosdidier
authors.forename: Laurent
authors.initials: L
authors.lastname: Fourcade
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bonnet
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
mesh_terms: D054058:Acute Coronary Syndrome / Q000601:surgery*; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000139:chemically induced* / Q000235:genetics*; D000068799:Prasugrel Hydrochloride; D011446:Prospective Studies; D012307:Risk Factors; D013876:Thiophenes / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D010879:Piperazines; D013876:Thiophenes; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000068799:Prasugrel Hydrochloride