Positive clinical response to clopidogrel is independent of paraoxonase 1 Q192R and CYP2C19 genetic variants

J Clin Pharmacol. 2014 Aug;54(8):843-9. doi: 10.1002/jcph.275. Epub 2014 Feb 14.

Abstract

There is increasing controversy about the influence of serum paraoxonase type 1 and cytochrome CYP2C19 in the conversion of clopidogrel to its pharmaceutically active metabolite. The effect of concomitant medication with the proton pump inhibitor omeprazole has been also subject of intense scrutiny. We present a cohort of 263 patients receiving anti-platelet aggregation treatment with clopidogrel and aspirin for 1 year. The paraoxonase 1 gene Q192R variant along with the presence of CYP2C19*2 and *3 loss of function alleles, concomitant medication with proton pump inhibitors and known cardiovascular risk factors were examined to determine their influence in disease relapse due to an ischaemic event during the 12 month treatment period. The low number of patients suffering a relapse (20 out of 263), indicates that double anti-aggregation therapy with aspirin and clopidogrel was very effective in our patients. Among the relapsers, evidence of coronary heart disease was the most influencial factor affecting response to therapy, while the presence of the paraoxonase 1 Q192R variant, loss of function of CYP2C19, and concomitant medication with omeprazole were non-significant.

Keywords: CYP2C19; aspirin; clopidogrel; omeprazole; paraoxonase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Angina Pectoris / drug therapy
  • Angina Pectoris / epidemiology
  • Angina Pectoris / genetics
  • Aryldialkylphosphatase / genetics*
  • Aspirin / administration & dosage*
  • Clopidogrel
  • Cohort Studies
  • Coronary Disease / drug therapy
  • Coronary Disease / epidemiology
  • Coronary Disease / genetics
  • Cytochrome P-450 CYP2C19 / genetics*
  • Cytochrome P-450 CYP2C19 Inhibitors / administration & dosage
  • Drug Therapy, Combination
  • Female
  • Genetic Variation
  • Genotype
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / genetics
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Proton Pump Inhibitors / administration & dosage
  • Recurrence
  • Risk Factors
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Treatment Outcome

Substances

  • Cytochrome P-450 CYP2C19 Inhibitors
  • Platelet Aggregation Inhibitors
  • Proton Pump Inhibitors
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Aryldialkylphosphatase
  • PON1 protein, human
  • Ticlopidine
  • Aspirin