title: CYP2C19*2 and prognosis after an acute coronary syndrome: Insights from a Portuguese center.
abstract: BACKGROUND
  Clopidogrel requires oxidation dependent on the cytochrome P450 enzyme 2C19 (CYP2C19) to form its active metabolite. The importance of loss-of-function alleles (particularly CYP2C19*2, 681G>A) in poor platelet response to clopidogrel is well recognized.
  
  
  OBJECTIVE
  To investigate the prevalence and prognostic impact of the CYP2C19*2 allele in a local acute coronary syndrome (ACS) population.
  
  
  METHODS
  We performed a prospective, longitudinal study of 95 patients admitted for an ACS between March and October 2009 to a single coronary care unit. Patients aged under 75 who survived hospital stay and for whom clopidogrel was prescribed were included. At discharge, CYP2C19 was genotyped using a commercially available kit. Patients were divided into two groups: Group A (non-carriers, normal metabolizers, CYP2C19*1/*1), n=69; and Group B (carriers, slow metabolizers, CYP2C19*2/*1 or *2/*2), n=26. The primary endpoint was a combined outcome of cardiovascular death, non-fatal myocardial infarction or re-admission for unstable angina; median follow-up was 136.0 (79.0-188.0) days.
  
  
  RESULTS
  The median age of the population was 62.0 (51.0-68.0) years, and 83.2% were male. The CYP2C19*2 (A) allele had a frequency of 14.2%. There were no differences between the groups with respect to demographic data or history of cardiovascular disease. Coronary anatomy, left ventricular ejection fraction and renal function were also similar. The groups were also homogenous with respect to GRACE risk score (118.0 (95.0-136.5) vs. 115.0 (96.0-133.0), p=0.68), medical treatment and percutaneous revascularization during hospital stay. Event-free survival was higher for Group A (94.0% vs. 75.0%, log-rank p=0.010). Three readmissions for MI were documented, all in the slow metabolizers group.
  
  
  CONCLUSIONS
  In our ACS population, the CYP2C19*2 allele was a medium-term prognostic marker.
authors.affiliation: Serviço de Cardiologia, Hospitais da Universidade de Coimbra, Coimbra, Portugal. rogeriopteixeira@gmail.com
authors.forename: Rogério
authors.initials: R
authors.lastname: Teixeira
authors.forename: Pedro
authors.initials: P
authors.lastname: Monteiro
authors.forename: Gilberto
authors.initials: G
authors.lastname: Marques
authors.forename: João
authors.initials: J
authors.lastname: Pego
authors.forename: Margarida
authors.initials: M
authors.lastname: Lourenço
authors.forename: Carlos
authors.initials: C
authors.lastname: Tavares
authors.forename: Alda
authors.initials: A
authors.lastname: Reboredo
authors.forename: Sílvia
authors.initials: S
authors.lastname: Monteiro
authors.forename: Francisco
authors.initials: F
authors.lastname: Gonçalves
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ferreira
authors.forename: Mário
authors.initials: M
authors.lastname: Freitas
authors.forename: Graça
authors.initials: G
authors.lastname: Ribeiro
authors.forename: Luís A
authors.initials: LA
authors.lastname: Providência
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011174:Portugal; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19