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Clinical impact of preemptive pharmacogenomic testing on antiplatelet therapy in a real-world setting

European Journal of Human Genetics (2024)Cite this article

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Abstract

CYP2C19 genotyping to guide antiplatelet therapy after patients develop acute coronary syndromes (ACS) or require percutaneous coronary interventions (PCIs) reduces the likelihood of major adverse cardiovascular events (MACE). Evidence about the impact of preemptive testing, where genotyping occurs while patients are healthy, is lacking. In patients initiating antiplatelet therapy for ACS or PCI, we compared medical records data from 67 patients who received CYP2C19 genotyping preemptively (results >7 days before need), against medical records data from 67 propensity score-matched patients who received early genotyping (results within 7 days of need). We also examined data from 140 patients who received late genotyping (results >7 days after need). We compared the impact of genotyping approaches on medication selections, specialty visits, MACE and bleeding events over 1 year. Patients with CYP2C19 loss-of-function alleles were less likely to be initiated on clopidogrel if they received preemptive rather than early or late genotyping (18.2%, 66.7%, and 73.2% respectively, p = 0.001). No differences were observed by genotyping approach in the number of specialty visits or likelihood of MACE or bleeding events (all p > 0.21). Preemptive genotyping had a strong impact on initial antiplatelet selection and a comparable impact on patient outcomes and healthcare utilization, compared to genotyping ordered after a need for antiplatelet therapy had been identified.

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Fig. 1: Escalation and de-escalation of antiplatelet therapy.
Fig. 2: Cumulative incidence of major adverse cardiovascular events and bleeding events in patients with CYP2C19 loss of function alleles.

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The data underlying this article cannot be shared publicly due to the privacy of individuals that participated in the study.

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Acknowledgements

Members of the Imagenetics METRICS TEAM. Sanford Health: Jordan Baye, Colette Free, Catherine Hajek, Kristen Jacobsen, Mary Kara, Amanda Massmann, Jennifer Morgan, Marian Petrasko, Natasha Petry, Muhammad Hamza Saad Shaukat, April Schultz, Rebecca Scott, Garret Spindler, Adam Stys, Tomasz Stys, Joel Van Heukelom, Max Weaver, and Elizabeth Wheeler. Harvard Pilgrim Health Care Institute: Kurt Christensen, Lauren Galbraith, Madison Hickingbotham, Jessica LeBlanc, and Emilie Zoltick. Brigham and Women’s Hospital: Robert Green, Charlene Preys and Carrie Zawatsky. National Institutes of Health: Leila Jamal.

Funding

This work was supported by the National Institutes of Health [K01-HG009173 to KDC] and the Imagenetics Initiative and Sanford Chip Program from Sanford Health.

Author information

Author notes

  1. These authors contributed equally: Amanda Massmann, Kurt D. Christensen.

Authors and Affiliations

  1. Sanford Imagenetics, Sioux Falls, SD, 57105, USA

    Amanda Massmann, Joel Van Heukelom, April Schultz, Catherine Hajek & Max Weaver

  2. Department of Internal Medicine, University of South Dakota School of Medicine, Vermillion, SD, 57069, USA

    Amanda Massmann, Joel Van Heukelom, April Schultz, Adam Stys & Tomasz P. Stys

  3. Broad Institute of Harvard and MIT, Cambridge, MA, 02141, USA

    Kurt D. Christensen & Robert C. Green

  4. PRecisiOn Medicine Translational Research (PROMoTeR) Center, Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, MA, 02215, USA

    Kurt D. Christensen, Ann Chen Wu, Madison R. Hickingbotham & Emilie S. Zoltick

  5. Department of Population Medicine, Harvard Medical School, Boston, MA, 02215, USA

    Kurt D. Christensen & Ann Chen Wu

  6. Minneapolis Heart Institute/Abbott Northwestern Hospital Institute, Minneapolis, MN, 55407, USA

    Muhammad Hamza Saad Shaukat

  7. Sanford Cardiovascular Institute, Sioux Falls, SD, 57105, USA

    Muhammad Hamza Saad Shaukat, Adam Stys & Tomasz P. Stys

  8. Helix OpCo, LLC, San Mateo, CA, 94401, USA

    Catherine Hajek

  9. Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, 02115, USA

    Robert C. Green

  10. Ariadne Labs, Boston, MA, 02215, USA

    Robert C. Green

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Contributions

Conceptualization: A.M., J.V.H., R.C.G., C.H., M.R.H., E.S.Z., K.D.C., A.J.S.; Data curation: A.M., J.V.H., M.R.H., K.D.C., A.J.S.; Formal analysis: M.R.H., K.D.C. M.W.; Funding acquisition: R.C.G., C.H., K.D.C., A.J.S.; Investigation: A.M., J.V.H., M.R.H., E.S.Z., K.D.C., A.J.S., M.H.S., A.S., T.S.; Methodology: A.M., J.V.H., M.R.H., A.C.W., E.S.Z., K.D.C., A.J.S., M.H.S., A.S., T.S.; Project administration: C.H., M.R.H., A.J.S.; Supervision: K.D.C., A.J.S.; Validation: A.M., J.V.H.; Writing-original draft: A.M., J.V.H., M.R.H., E.S.Z., K.D.C., A.J.S.; Writing–review & editing: A.M., J.V.H., R.C.G., C.H., M.R.H., E.A.L, A.C.W., E.S.Z., K.D.C., A.J.S., M.W., M.H.S., A.S., T.S.

Corresponding author

Correspondence to Amanda Massmann.

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Competing interests

KDC, ESZ, and MRH were supported by a research grant from Sanford Health. CH is an employee of Helix OpCo, LLC. RCG has received compensation for advising Allelica, Atria, Fabric, Genome Web, Genomic Life, and VinBigData and is co-founder of Genome Medical and Nurture Genomics. The remaining authors have nothing to disclose.

Ethics

The research protocol was approved by the Sanford Health and Harvard Pilgrim Health Care Institute Institutional Review Boards. Individual-level patient data were deidentified before being provided to the study team, and informed consent was not required.

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Massmann, A., Christensen, K.D., Van Heukelom, J. et al. Clinical impact of preemptive pharmacogenomic testing on antiplatelet therapy in a real-world setting. Eur J Hum Genet (2024). https://doi.org/10.1038/s41431-024-01567-1

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