Cytochrome p450 gene variants, race, and mortality among clopidogrel-treated patients after acute myocardial infarction

Sharon Cresci, Jeremiah P. Depta, Petra A. Lenzini, Allie Y. Li, David E. Lanfear, Michael A. Province, John A. Spertus, Richard G. Bach

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Background-Clopidogrel is recommended after acute myocardial infarction but has variable efficacy and safety, in part related to the effect of cytochrome P450 (CYP) polymorphisms on its metabolism. The effect of CYP polymorphisms on cardiovascular events among clopidogrel-treated patients after acute myocardial infarction remains controversial, and no studies to date have investigated the association of CYP variants with outcomes in black patients. Methods and Results-Subjects (2732: 2062 whites; 670 blacks) hospitalized with acute myocardial infarction enrolled in the prospective, multicenter TRIUMPH study were genotyped for CYP polymorphisms. The majority of whites (79%) and blacks (64.4%) were discharged on clopidogrel. Among whites, carriers of the loss-of-function CYP2C192 allele had significantly increased 1-year mortality (adjusted hazards ratio [HR]: 1.70; confidence interval [CI]: 1.01-2.86; P=0.046) and a trend toward increased rate of recurrent MI (adjusted HR: 2.10; CI: 0.95-4.63; P=0.066). Among blacks, increased 1-year mortality was associated with the gain-of-function CYP2C1917 allele (adjusted HR for 1/17 versus 1/1: 2.02; CI: 0.92-4.44; 17/17 versus 1/1: 8.97; CI: 3.34-24.10; P>0.0001) and the CYP1A21C allele (adjusted HR for 1/1C versus 1/1: 1.89; CI: 0.85-4.22; 1C/1C versus 1/1: 4.96; CI: 1.69-14.56; P=0.014). Bleeding events were significantly more common among black carriers of CYP2C1917 or CYP1A21C. Conclusions-Both loss-of-function and gain-of-function CYP polymorphisms affecting clopidogrel metabolism are associated with increased mortality among clopidogrel-treated patients after acute myocardial infarction; the specific polymorphism and the putative mechanism vary according to race.

Original languageEnglish
Pages (from-to)277-286
Number of pages10
JournalCirculation: Cardiovascular Genetics
Volume7
Issue number3
DOIs
StatePublished - Jun 2014

Keywords

  • Clopidogrel
  • Genetic variation
  • Mortality
  • Myocardial infarction

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