Clinical, pharmacokinetic, and pharmacogenetic determinants of clopidogrel resistance in korean patients with acute coronary syndrome

Kyoung Jin Park, Hae Sun Chung, Suk Ran Kim, Hee Jin Kim, Ju Yong Han, Soo Youn Lee

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Background: Clopidogrel has been widely used to prevent recurrent ischemia in patients with acute coronary syndrome (ACS). However, inter-individual variability in response to Clopidogrel has been a problem in the clinical setting. The aim of the present study was to investigate the frequency of Clopidogrel resistance and to determine the clinical, pharmacokinetic and pharmacogenetic factors for Clopidogrel resistance in Korean patients with ACS. Methods: Clinical information, such as the underlying diseases and concurrent medications, of 114 patients with ACS who received Clopidogrel therapy was studied. The degree of inhibition of platelets was assessed using the VerifyNow assay (Accumetrics, USA). The patients who showed less than 20% inhibition of platelets were defined as non-responders to Clopidogrel treatment. Steady state plasma concentrations of Clopidogrel were measured using HPLC/tandem mass spectrometry. CYP209 genotyping was also performed. Results: A wide inter-Individual variability was observed in platelet inhibition (0-76%); 56 patients (49%) showed less than 20% inhibition. There were no differences between the patients' history of diabetes mellitus and concurrent medications as well as the plasma concentrations of Clopidogrel of the responders and non-responders. CYP2C19 variants, including CfP2C19*2 and CYP2C19*3, were more commonly observed in the non-responders than in the responders (P value < 0.0001 ). Conclusions: The response to Clopidogrel was highly variable in Korean patients with ACS. The results of the present study confirmed that the genetic polymorphism of CYP2C19 could be important in Clopidogrel response. However, further studies are required to investigate other likely factors involved in Clopidogrel resistance.

Original languageEnglish
Pages (from-to)91-94
Number of pages4
JournalKorean Journal of Laboratory Medicine
Volume31
Issue number2
DOIs
StatePublished - Apr 2011

Keywords

  • Acute coronary syndrome
  • CYP2C19
  • Clopidogrel resistance
  • Korean
  • Platelet inhibition

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