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Microfluidics in Assessing Platelet Function
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CYP2C19 genotype, clopidogrel metabolism, platelet function, and cardiovascular events: a systematic review and

Michael V Holmes1, Pablo Perel, Tina Shah

  • 1Genetic Epidemiology Group, Department of Epidemiology and Public Health, University College London, 1-19 Torrington Pl, London, WC1E 6BT, United Kingdom. mvholmes@gmail.com

JAMA
|December 29, 2011
PubMed

Insights

CYP2C19 genotype testing may influence clopidogrel response, but this systematic review found no significant association with cardiovascular events. Evidence for genotype-guided antiplatelet therapy remains insufficient for widespread clinical use.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Clinical Chemistry

Background:

  • The US FDA recommended CYP2C19 genotyping before prescribing clopidogrel.
  • Major cardiology organizations questioned the sufficiency of evidence for this recommendation.

Purpose of the Study:

  • To systematically review and meta-analyze evidence linking CYP2C19 genotype to clopidogrel response.
  • To evaluate the impact of genotype on clinical outcomes like cardiovascular events and bleeding.

Main Methods:

  • Systematic review and meta-analysis of studies from PubMed and EMBASE (up to October 2011).
  • Included studies reporting clopidogrel metabolism, platelet reactivity, clinical outcomes, and CYP2C19 genotype.
  • Extracted data on study design, genotyping methods, and outcomes; assessed bias.

Main Results:

  • 32 studies (42,016 patients) were analyzed, reporting CVD events, stent thrombosis, and bleeding.
  • In treatment-only analyses, specific CYP2C19 genotypes correlated with altered clopidogrel metabolism and platelet inhibition.
  • However, effect-modification studies showed no significant genotype association with clopidogrel's effect on CVD or bleeding outcomes.

Conclusions:

  • While CYP2C19 genotype influences clopidogrel responsiveness, no significant association was found with overall cardiovascular events.
  • Evidence for routine CYP2C19 genotype testing to guide clopidogrel therapy is not robust.
  • Limitations included potential bias and inconsistencies in genotype nomenclature.
Abstract

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