Genetic causes of clopidogrel nonresponsiveness: which ones really count?

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Published on: April 1, 2019

Kathryn M Momary1, Michael P Dorsch, Eric R Bates

  • 1Department of Pharmacy Practice, Mercer University College of Pharmacy and Health Sciences, Atlanta, Georgia 30341-4155, USA. momary_km@mercer.edu

Pharmacotherapy
|February 26, 2010
PubMed

Insights

Genetic variations in CYP2C19 and ABCB1 impact clopidogrel effectiveness. Patients with specific CYP2C19 variants show reduced response due to impaired active metabolite formation. Routine genetic testing is not yet recommended.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Pharmacology

Background:

  • Clopidogrel is a crucial antiplatelet medication for cardiovascular disease management.
  • It functions as a prodrug, requiring metabolic activation by cytochrome P450 (CYP) enzymes.
  • Interindividual variability in clopidogrel response is a significant clinical concern.

Purpose of the Study:

  • To review genetic factors influencing clopidogrel responsiveness.
  • To focus on outcomes-based studies examining genetic polymorphisms.
  • To summarize the genetic causes of clopidogrel nonresponsiveness.

Main Methods:

  • Literature review of English-language studies (1990-2008) from MEDLINE.
  • Inclusion of studies investigating genetic variations and clopidogrel response.
  • Analysis of outcomes-based studies on genetic polymorphisms.

Main Results:

  • CYP2C19 gene polymorphisms, particularly alleles CYP2C19*2 and *3, significantly impair clopidogrel activation and responsiveness.
  • The adenosine 5'-triphosphate-binding cassette gene, ABCB1, also contributes to response variability.
  • Combined analysis of CYP2C19 and ABCB1 genotypes improved prediction of nonresponsiveness in one study.

Conclusions:

  • Genetic variations in CYP2C19 are a primary driver of clopidogrel nonresponsiveness.
  • ABCB1 polymorphisms may further refine the prediction of clopidogrel response.
  • Current logistic and cost factors preclude routine genetic screening for clopidogrel responsiveness.

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