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A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene
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2025 Acute Coronary Syndrome Guideline: Missing the Boat on CYP2C19 Genotyping

Larisa H Cavallari1, Craig R Lee2,3, Amber L Beitelshees4

  • 1Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision, Medicine College of Pharmacy University of Florida Gainesville FL USA.

Journal of the American Heart Association
|May 6, 2026
PubMed

Insights

The 2025 acute coronary syndrome guideline omits CYP2C19 genotyping recommendations. Genetic testing can optimize P2Y12 inhibitor selection, balancing atherothrombotic event risk and bleeding risk.

Area of Science:

  • Cardiology
  • Pharmacogenomics
  • Clinical Guidelines

Background:

  • The 2025 acute coronary syndrome guideline prioritizes bleeding risk reduction with antiplatelet therapy.
  • It does not include recommendations for CYP2C19 genotyping, despite its known impact on clopidogrel effectiveness.

Purpose of the Study:

  • To highlight the importance of CYP2C19 genotyping in guiding P2Y12 inhibitor selection for acute coronary syndrome (ACS) patients.
  • To advocate for the inclusion of CYP2C19 genetic testing recommendations in future ACS guidelines.

Main Methods:

  • Review of evidence on CYP2C19 loss-of-function alleles and P2Y12 inhibitor efficacy and safety.
  • Analysis of current ACS guideline recommendations in light of pharmacogenomic data.

Main Results:

  • CYP2C19 loss-of-function alleles significantly affect clopidogrel efficacy.
  • CYP2C19-guided therapy optimizes outcomes: clopidogrel is safer in non-carriers, while prasugrel/ticagrelor are more effective in carriers.
  • An American Heart Association Scientific Statement supports CYP2C19 genetic testing.

Conclusions:

  • CYP2C19 genotyping should guide P2Y12 inhibitor selection in ACS patients, particularly those at high bleeding risk.
  • Future ACS guidelines must incorporate recommendations for CYP2C19 genetic testing to improve patient outcomes.

Keywords:
CYP2C19acute coronary syndromeclopidogrelgenotype

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