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Point of care CYP2C19 genotyping after percutaneous coronary intervention

The Pharmacogenomics Journal volume 22, pages 303–307 (2022)Cite this article

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Abstract

Loss-of-function CYP2C19 variants are associated with increased cumulative ischemic outcomes warranting CYP2C19 genotyping prior to clopidogrel administration. TAILOR-PCI was an international, multicenter (40 sites), prospective, randomized trial comparing rapid point of care (POC) genotype-guided vs. conventional anti-platelet therapy. The performance of buccal-based rapid CYP2C19 genotyping performed by non-laboratory-trained staff in TAILOR-PCI was assessed. Pre-trial training and evaluation involved rapid genotyping of 373 oral samples, with 99.5% (371/373) concordance with Sanger sequencing. During TAILOR-PCI, 5302 patients undergoing PCI were randomized to POC rapid CYP2C19 *2, *3, and *17 genotyping versus no genotyping. At 12 months post-PCI, TaqMan genotyping determined 99.1% (2,364/2,385) concordance with the POC results, with 90.7–98.8% sensitivity and 99.2–99.6% specificity. In conclusion, non-laboratory personnel can be successfully trained for on-site instrument operation and POC rapid genotyping with analytical accuracy and precision across multiple international centers, thereby supporting POC genotyping in patient-care settings, such as the cardiac catheterization laboratory.

Clinical Trial Registration: https://www.clinicalTrials.gov (Identifier: NCT01742117).

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Fig. 1: Validation and performance of spartan rapid CYP2C19 genotyping in TAILOR-PCI.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by the National Institutes of Health (U01HL128606 and U01HL128626 to N.L.P and M.E.F).

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Authors and Affiliations

  1. Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA

    Linnea M. Baudhuin & Laura J. Train

  2. St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada

    Shaun G. Goodman

  3. Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada

    Shaun G. Goodman

  4. Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, USA

    Gary E. Lane

  5. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

    Ryan J. Lennon

  6. Worldwide Network for Innovation in Clinical Education and Research (WNICER) Institute, New York, NY, USA

    Verghese Mathew

  7. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA

    Vishakantha Murthy, Charanjit S. Rihal & Naveen L. Pereira

  8. Columbia University Medical Center, New York Presbyterian Hospital, New York, NY, USA

    Tamim M. Nazif

  9. University of Ottawa Heart Institute, Ottawa, ON, Canada

    Derek Y. F. So

  10. Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA

    John P. Sweeney

  11. Department of Laboratory Medicine, University of California, San Francisco, CA, USA

    Alan H. B. Wu

  12. Peter Munk Cardiac Centre and Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto, ON, Canada

    Michael E. Farkouh

Authors
  1. Linnea M. Baudhuin
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  2. Laura J. Train
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  3. Shaun G. Goodman
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  4. Gary E. Lane
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  6. Verghese Mathew
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  9. Derek Y. F. So
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  11. Alan H. B. Wu
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  12. Charanjit S. Rihal
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  13. Michael E. Farkouh
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  14. Naveen L. Pereira
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Contributions

LMB was the principal investigator and takes primary responsibility for the manuscript. LMB, LJT, SGF, RJL, CSR, MEF, and NLP were involved in the conception and design, collection, and compilation of data, data analysis and writing the manuscript; GEL, VM, VM, TMN, DYFS, JPS, and AHBW in data analysis, strategic suggestions, and writing the manuscript.

Corresponding author

Correspondence to Linnea M. Baudhuin.

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Competing interests

MEF reports research grants from Amgen, Novartis, and Novo Nordisk. Dr. So reports unrestricted grant support from Spartan Biosciences and Fujimori Kogyo and is on advisory boards for AztraZeneca Canada, Bayer Canada, JAMP/Orimed Pharma, and HLS Therapeutics. SGG reports research grant support and/or speaker/consulting honoraria from: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo/American Regent, Eli Lilly, JAMP Pharma, Pfizer, Servier, Valeo Pharma; and salary support/honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre. The remaining authors have no disclosures to report.

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Baudhuin, L.M., Train, L.J., Goodman, S.G. et al. Point of care CYP2C19 genotyping after percutaneous coronary intervention. Pharmacogenomics J 22, 303–307 (2022). https://doi.org/10.1038/s41397-022-00278-4

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  • DOI: https://doi.org/10.1038/s41397-022-00278-4

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