Pre-procedural platelet reactivity after clopidogrel loading in korean patients undergoing scheduled percutaneous coronary intervention

J Atheroscler Thromb. 2010 Nov 27;17(11):1122-31. doi: 10.5551/jat.4564. Epub 2010 Aug 17.

Abstract

Aim: Pre-procedural platelet reactivity (PR) in Korean patients may be greater because the CYP2C19*2 and *3 variant alleles are more common in Korean patients than in Caucasians. We investigated the level of PR and the prevalence of high post-clopidogrel platelet reactivity (HPPR) after a routine loading dose (LD) of clopidogrel in Korean patients.

Methods: We assessed the PR level at 12 to 24 hours after a 300-mg LD of clopidogrel in 215 patients undergoing scheduled percutaneous coronary intervention (PCI) (available CYP2C19 genotyping: n =176). PR was measured by conventional aggregometry and VerifyNow. Based on a previous study, HPPR was defined as a 5 µmol/L ADP-induced maximal PR >50%.

Results: With 5 and 20 µmol/L ADP stimuli, maximal PR were 48.7 ± 17.1% and 62.1 ± 15.7%, respectively, and the prevalence of HPPR reached 52.1%. The highest quartile cut-offs of 5 and 20 µmol/L ADP-induced PR(max) were 64% and 75%, respectively. P2Y₁₂ reaction unit (PRU) was 274 ± 76, and 69.8% (n =150) showed PRU ≥240. A carrier of at least one CYP2C19 variant allele showed higher PRs than non-carriers. In multivariate regression analysis, carriage of the CYP2C19 variant allele (*2 or *3) was determined to be a significant predictor of HPPR (odds ratio 4.202, 95% confidence interval 1.996 to 8.850, p< 0.001).

Conclusions: Korean patients undergoing scheduled PCI cannot achieve adequate pre-procedural platelet inhibition from a 300-mg LD of clopidogrel, which is related with a higher prevalence of the CYP2C19 mutant allele.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / genetics
  • Acute Coronary Syndrome / therapy*
  • Aged
  • Angioplasty, Balloon, Coronary*
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics
  • Platelet Activation / drug effects*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Polymorphism, Genetic / genetics
  • Republic of Korea
  • Risk Factors
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Treatment Outcome

Substances

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