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The pharmacogenetics of antiplatelet agents: towards personalized therapy?

Nature Reviews Cardiology volume 8, pages 560–571 (2011)Cite this article

Subjects

Abstract

Considerable variability exists in how individual patients respond to oral antiplatelet therapy, specifically to aspirin and to P2Y12-receptor inhibitors such as clopidogrel. This variability translates to differences in clinical outcomes and might in part be as a result of common variation within genes that are involved in the absorption, metabolic activation, and biological activity of these medications. The field of pharmacogenetics has yielded several genetic loci that predict variation in patient response to antiplatelet therapies. The most robust data indicate an association between loss-of-function alleles of the CYP2C19 gene and adverse outcomes among high-risk patients treated with clopidogrel. However, several fundamental questions surrounding the information gained from genotyping and the efficacy of modifying therapy on the basis of testing remain unanswered. Routine genetic testing for platelet responsiveness cannot, therefore, be recommended for clinical decision-making. Ongoing and future clinical trials might provide evidence to support a change in practice towards pharmacogenetic-based selection of antiplatelet therapy.

Key Points

  • Substantial interindividual variability in response to antiplatelet medications translates to differences in clinical outcomes

  • Controversy surrounds the definition and prevalence of 'resistance' to aspirin, and the role of genetic variability in the response to this drug is unclear

  • Several genetic variants have been shown to predict heterogeneity in clopidogrel response, with the most robust data existing for variants of the CYP2C19 gene

  • Until favorable, scientifically-derived data are available, routine genetic testing for platelet responsiveness cannot be recommended for clinical decision-making

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Figure 1: Platelet activation and variability in tests for aspirin resistance.
Figure 2: Variability in response to thienopyridine platelet inhibition.

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Acknowledgements

The authors would like to thank Jeffery B. Washam (Duke University Medical Center, NC, USA) for his editorial contributions and valuable feedback on this manuscript.

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  1. Division of Cardiology, Duke University School of Medicine, 2400 Pratt Street, DUMC 3850, Durham, 27710, NC, USA

    Tariq Ahmad, Deepak Voora & Richard C. Becker

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  1. Tariq Ahmad
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Contributions

T. Ahmad researched the data for the article. All the authors contributed equally to discussions of the content and to writing the article. D. Voora and R. C. Becker reviewed and edited the manuscript before submission.

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Correspondence to Richard C. Becker.

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Competing interests

R. C. Becker is a consultant for the following companies: AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Portola Pharmaceuticals, and Regardo Biosciences, and has received grants or research support from AstraZeneca and Regardo Biosciences. The other authors declare no competing interests.

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Ahmad, T., Voora, D. & Becker, R. The pharmacogenetics of antiplatelet agents: towards personalized therapy?. Nat Rev Cardiol 8, 560–571 (2011). https://doi.org/10.1038/nrcardio.2011.111

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