title: Clinical outcomes associated with proton pump inhibitor use among clopidogrel-treated patients within CYP2C19 genotype groups following acute myocardial infarction.
abstract: We examined clinical outcomes with proton pump inhibitors (PPI) use within CYP2C19 genotype groups during clopidogrel treatment following acute myocardial infarction (AMI). 2062 patients were genotyped for CYP2C19*2 and *17 variants in TRIUMPH. 12 month clinical outcomes were analyzed among patients discharged on clopidogrel within CYP2C19*2 carrier, CYP2C19*17 carrier, and CYP2C19*1 homozygote genotype groups. PPI use was not associated with a difference in mortality. Among clopidogrel-treated Caucasians following AMI, PPI use was associated with a significantly higher rate of cardiac rehospitalization (HR 1.62, 95% CI 1.19-2.19; P=0.002) compared with no PPI use. PPI users who were carriers of the CYP2C19*17 variant experienced significantly higher rates of cardiac rehospitalization (HR 2.05, 95% CI 1.26-3.33; P=0.003), carriers of the CYP2C19*2 variant had a trend toward increased 1-year cardiac rehospitalization (HR 1.69, 95% CI 0.95-2.99; P=0.07), while no significant differences were observed among CYP2C19*1 homozygotes. These results indicate that the risks associated with PPI use among clopidogrel-treated Caucasian post-MI patients are impacted by CYP2C19 genotype, and suggest knowledge of genotype may be useful for personalizing PPI use among patients following AMI to reduce rehospitalization.
authors.affiliation: Washington University School of Medicine, Department of Medicine, St Louis, MO, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Depta
authors.affiliation: Washington University School of Medicine, Department of Genetics, St Louis, MO, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Lenzini
authors.affiliation: Heart and Vascular Institute, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Lanfear
authors.affiliation: Duke Clinical Research Institute, Duke, Durham, NC, USA.
authors.forename: T Y
authors.initials: TY
authors.lastname: Wang
authors.affiliation: Saint Luke's Mid America Heart Institute and the University of Missouri-Kansas City, Kansas City, MO, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Spertus
authors.affiliation: Washington University School of Medicine, Department of Medicine, St Louis, MO, USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Bach
authors.affiliation: 1] Washington University School of Medicine, Department of Medicine, St Louis, MO, USA [2] Washington University School of Medicine, Department of Genetics, St Louis, MO, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cresci
mesh_terms: D000328:Adult; D000368:Aged; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine