Korean J Lab Med.  2011 Apr;31(2):91-94. 10.3343/kjlm.2011.31.2.91.

Clinical, Pharmacokinetic, and Pharmacogenetic Determinants of Clopidogrel Resistance in Korean Patients with Acute Coronary Syndrome

• Park KJ
• Chung HS
• Kim SR
• Kim HJ
• Han JY
• Lee SY

• KMID: 1094346
• DOI: http://doi.org/10.3343/kjlm.2011.31.2.91

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. CYP2C19 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 CYP2C19*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.

Keyword

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

MeSH Terms

Acute Coronary Syndrome/complications/*drug therapy/genetics
Adult
Aged
Aged, 80 and over
Aryl Hydrocarbon Hydroxylases/antagonists & inhibitors/genetics/metabolism
Asian Continental Ancestry Group/*genetics
Diabetes Complications
Drug Resistance
Female
Genotype
Humans
Male
Middle Aged
Platelet Aggregation Inhibitors/blood/pharmacokinetics/*therapeutic use
Polymorphism, Genetic
Republic of Korea
Ticlopidine/*analogs & derivatives/blood/pharmacokinetics/therapeutic use

Figure

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  Fig. 1 Comparison of the percentage inhibition of platelet aggregation and CYP2C19 polymorphisms.

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