The CYP2C19 genotype does not impact the long-term prognosis of patients with coronary artery disease

Atherosclerosis. 2013 Mar;227(1):106-11. doi: 10.1016/j.atherosclerosis.2012.12.028. Epub 2013 Jan 2.

Abstract

Background: Cytochrome P450 (CYP) 2C19 plays a key role in clopidogrel activation and thus impacts the clinical outcome of patients with coronary artery disease (CAD). However, the majority of patients with CAD gradually discontinue clopidogrel after one year of discharge. This study explored whether the CYP2C19 gene polymorphism was associated with clinical events in patients with CAD after one year of discharge.

Method: Between July 2008 and July 2009, 506 patients with CAD that was confirmed by coronary angiography were enrolled in this study, and their CYP2C19 genotype was determined. The primary endpoint events included cardiovascular death, nonfatal myocardial infarction and nonfatal stroke. The secondary endpoint events included the components of the primary endpoint events, all-cause mortality and recurrent revascularisation.

Result: The baseline clinical characteristics of CYP2C19*2-mutation carriers (homozygous *2/*2, n = 49; heterozygous *1/*2, n = 222) and non-carriers (wild-type allele *1/*1, n = 235) were comparable. The follow-up results showed that the incidence of adverse cardiovascular events within one year of discharge was significantly higher in carriers of the CYP2C19*2 homozygous genotype (*2/*2) than non-carriers (12.24% vs. 3.83%, adjusted hazard ratio (HR) 4.651, 95% confidence interval (CI) 1.566-13.814, p = 0.006). However, the follow-up results after one year of discharge showed that the risk of the CYP2C19*2 homozygous genotype were significantly reduced. New primary endpoint events during the second year after discharge had no significant correlation with the CYP2C19 genotype.

Conclusion: The risk of cardiovascular events in CAD patients with a homozygous CYP2C19*2 mutation was significantly higher than in other patients within the first year after discharge. However, the adverse impact of the CYP2C19*2 polymorphism was significantly reduced after one year of discharge.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Clopidogrel
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / mortality
  • Cytochrome P-450 CYP2C19
  • Female
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / metabolism
  • Polymorphism, Genetic
  • Prodrugs / metabolism
  • Prognosis
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / metabolism

Substances

  • Platelet Aggregation Inhibitors
  • Prodrugs
  • Clopidogrel
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine