Protective effect of the CYP2C19 *17 polymorphism with increased activation of clopidogrel on cardiovascular events

Am Heart J. 2010 Sep;160(3):506-12. doi: 10.1016/j.ahj.2010.06.039.


Background: The prodrug clopidogrel requires activation by cytochrome P-450 (CYP) enzymes for its antiplatelet effect. The genes encoding enzymes for clopidogrel activation are polymorphic, leading to reduced or increased function, depending on the respective genotype. Reduced-function alleles have been associated with an increase in cardiovascular events.

Methods: We tested the association of the presence of the ABCB1 (C/T) T-allele, CYP2C19*2 (G/A) A-allele, or CYP2C19*17 (C/T) T-allele with the primary end point of the need of clinically-driven target lesion revascularization (TLR) and the secondary end points of major adverse cardiovascular events (MACE; including death, myocardial infarction [MI], and TLR) at 1 year in a high-risk population of 928 patients with acute MI.

Results: Carriers of the CYP2C19*17 T-allele, with increased clopidogrel activation, had a 37% relative reduction in the TLR incidence, the primary end point (14.0% vs 22.3%, P = .002), and a 22% relative reduction of the secondary end point MACE (22.0% vs 28.1%, P = .04) compared with noncarriers, respectively. The association of the T-allele with TLR remained significant in the multivariate analysis (P = .001). The ABCB1 (C/T) and the CYP2C19*2 (G/A) polymorphisms were not associated with the incidence of TLR or MACE.

Conclusions: Based on the genetic analysis in a high-risk population of acute MI patients with interventional treatment and continuous clopidogrel therapy, our study found a protective effect for carriers of an increased-function CYP2C19*17 T-allele with significantly lower rates of TLR and MACE. T-allele carriers with acute MI and increased clopidogrel activation had significantly reduced clinical event rates.

MeSH terms

  • Aged
  • Alleles
  • Angioplasty, Balloon, Coronary
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Aryl Hydrocarbon Hydroxylases / physiology*
  • Biotransformation
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / therapy
  • Clopidogrel
  • Coronary Angiography
  • Coronary Restenosis / prevention & control
  • Cytochrome P-450 CYP2C19
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / therapy
  • Platelet Aggregation Inhibitors / pharmacokinetics*
  • Polymorphism, Genetic / physiology*
  • Recurrence
  • Reoperation
  • Stents
  • Stroke / genetics
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacokinetics


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