Evaluating the extent of reusability of CYP2C19 genotype data among patients genotyped for antiplatelet therapy selection

  • A Correction to this article was published on 03 August 2020

Abstract

Purpose

Genotype-guided antiplatelet therapy is increasingly being incorporated into clinical care. The purpose of this study is to determine the extent to which patients initially genotyped for CYP2C19 to guide antiplatelet therapy were prescribed additional medications affected by CYP2C19.

Methods

We assembled a cohort of patients from eight sites performingCYP2C19 genotyping to inform antiplatelet therapy. Medication orders were evaluated from time of genotyping through one year. The primary endpoint was the proportion of patients prescribed two or more CYP2C19 substrates. Secondary endpoints were the proportion of patients with a drug–genotype interaction and time to receiving a CYP2C19 substrate.

Results

Nine thousand one hundred ninety-one genotyped patients (17% nonwhite) with a mean age of 68 ± 3 years were evaluated; 4701 (51%) of patients received two or more CYP2C19 substrates and 3835 (42%) of patients had a drug–genotype interaction. The average time between genotyping and CYP2C19 substrate other than antiplatelet therapy was 25 ± 10 days.

Conclusions

More than half of patients genotyped in the setting of CYP2C19-guided antiplatelet therapy received another medication impacted by CYP2C19 in the following year. Given that genotype is stable for a patient’s lifetime, this finding has implications for cost effectiveness, patient care, and treatment outcomes beyond the indication for which it was originally performed.

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Fig. 1: Proportion of patients with two or more CYP2C19 substrate medication orders and gene–drug interactions.

Change history

  • 03 August 2020

    The original version of this Article contained an error in the spelling of the author Dominick J. Angiolillo, which was incorrectly given as Dominick P. Angiolillo. This has now been corrected in both the PDF and HTML versions of the Article.

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Acknowledgements

Funding for this work was provided by National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI) U01HG007775 (A.L.B.); American Heart Association 17MCPRP33400175 (J.M.S.); National Heart, Lung, and Blood Institute (NHLBI) K23HL143161 and Penn Center for Precision Medicine (S.T.); RO1HL092173 and K24HL133373, Clinical and Translational Science Award UL1TR000165, University of Alabama Birmingham’s Health Service Foundations’ General Endowment Fund and Hugh Kaul Personalized Medicine Institute (N.A.L., C.D.); the American Society of Health System Pharmacists, NIH UL1TR0000005, and by an Anonymous Donor (J.M.S. and P.E.E.), NIH/NHGRI U01HG007253 and U01HG010232 (J.F.P. and E.M.F.), NIH NHGRI U01 HG007269 and NIH National Center for Advancing Translational Sciences (NCATS) UL1 TR000064 (J.A.J. and L.H.C.).

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Correspondence to Amber L. Beitelshees PharmD, MPH.

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Disclosure

J.F.P. is a consultant for Color Genomics. T.C.S. is paid as a pharmacogenetics consultant for IU Health. D.J.A. declares that he has received consulting fees or honoraria from Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company and has received payments for participation in review activities from CeloNova and St Jude Medical. D.J.A. also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions, and Scott R. MacKenzie Foundation. F.F. declares that he has received consulting fees or honoraria from, AstraZeneca, Bayer, Sanofi. The other authors declare no conflicts of interest.

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Beitelshees, A.L., Stevenson, J.M., El Rouby, N. et al. Evaluating the extent of reusability of CYP2C19 genotype data among patients genotyped for antiplatelet therapy selection. Genet Med (2020). https://doi.org/10.1038/s41436-020-0894-2

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Key words

  • pharmacogenetics
  • CYP2C19