Skip to main content
SpringerLink
Log in

Development of a routine bedside CYP2C19 genotype assessment program for antiplatelet therapy guidance in a community hospital catheterization laboratory

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Genotype based personalized antiplatelet therapy in the setting of percutaneous coronary intervention (PCI) has been studied in clinical trials. Despite the demonstrated risk associated with CYP2C19 loss-of-function (LoF) carriage in clopidogrel-treated PCI patients, real-world implementation of genotyping for PCI has been low. The goal of the current study was to provide CYP2C19 genotype information to the interventionalist prior to the completion of the catheterization to facilitate immediate personalized antiplatelet therapy. Routine personalization of P2Y12 inhibitor therapy for PCI in a community hospital cardiac catheterization laboratory by POC genotyping with the SpartanRx system was first offered in February 2017. A best practice advisory (BPA) based on the Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 genotype and clopidogrel therapy was placed in the electronic health record prescription medication ordering system. By December 2019, 1,052 patients had CYP2C19 genotype testing, 429 patients underwent PCI with genotype guided antiplatelet therapy, and 250 patients underwent PCI without genotype testing and received antiplatelet therapy at the discretion of the treating physician. BPA compliance was 93. 87% of LoF allele carriers were prescribed ticagrelor or prasugrel whereas 96% of non-LoF allele carriers were prescribed clopidogrel. The genotyping results were available within 1 h and made immediately available for decision making by the interventional cardiologist. POC CYP2C19 genotyping is feasible in a community hospital catheterization laboratory and is associated with high rate of best practice compliance.

Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03040622

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Gurbel PA, Tantry US (2012) Do platelet function testing and genotyping improve outcome in patients treated with antithrombotic agents? Platelet function testing and genotyping improve outcome in patients treated with antithrombotic agents. Circulation 125:1276–1287

    Article  PubMed  Google Scholar 

  2. Lee Cr, Luzum JA, Sangkuhl K et al (2022) Clinical pharmacogenetics implementation consortium guideline for CYP2C19 genotype and clopidogrel therapy: 2022 update. Clin Pharmacol Ther 112:959–967

    Article  PubMed  Google Scholar 

  3. Mega JL, Simon T, Collet JP et al (2010) Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA 304:1821–1830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Claassens DMF, Bergmeijer TO, Vos GJA et al (2021) Clopidogrel versus ticagrelor or prasugrel after primary percutaneous coronary intervention according to CYP2C19 genotype: a popular genetics subanalysis. Circ Cardiovasc Interv 14:e009434

    Article  CAS  PubMed  Google Scholar 

  5. Mega JL, Close SL, Wiviott SD, Shen L et al (2010) Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis. Lancet 376:1312–1319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wallentin L, James S, Storey RF et al (2010) PLATO investigators. Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet 376:1320–1328

    Article  CAS  PubMed  Google Scholar 

  7. Shuldiner AR, O’Connell JR, Bliden KP et al (2009) Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 302:849–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Reese ES, Daniel C, Beitelshees AL, Onukwugha E (2012) Cost-effectiveness of cytochrome P450 2C19 genotype screening for selection of antiplatelet therapy with clopidogrel or prasugrel. Pharmacotherapy 32:323–332

    Article  PubMed  PubMed Central  Google Scholar 

  9. FDA Drug Safety Communication: reduced effectiveness of Plavix (clopidogrel) in patients who are poor metabolizers of the drug. Available at: https://www.fda.gov/Drugs/DrugSafety/Postmarket%20Drug%20Safety%20Information%20for%20Patients%20and%20Providers/ucm203888.htm Drug Safety Information for Patients and

  10. Scott SA, Sangkuhl K, Stein CM, Clinical Pharmacogenetics Implementation Consortium et al (2013) Clinical pharmacogenetics implementation consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther 94:317–323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Roberts JD, Wells GA, Le May MR et al (2012) Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial. Lancet 379:1705–1711

    Article  CAS  PubMed  Google Scholar 

  12. Zabalza M, Subirana I, Sala J, Lluis-Ganella C et al (2012) Meta-analyses of the association between cytochrome CYP2C19 loss- and gain-of-function polymorphisms and cardiovascular outcomes in patients with coronary artery disease treated with clopidogrel. Heart 98:100–108

    Article  CAS  PubMed  Google Scholar 

  13. Claassens DMF, Vos GJA, Bergmeijer TO et al (2019) A genotype-guided strategy for oral P2Y12 inhibitors in primary PCI. N Engl J Med 381:1621–1631

    Article  CAS  PubMed  Google Scholar 

  14. Pereira NL, Farkouh ME, So D et al (2020) Effect of genotype-guided oral P2Y12 inhibitor selection vs conventional clopidogrel therapy on ischemic outcomes after percutaneous coronary intervention: the TAILOR-PCI randomized clinical trial. JAMA 324:761–771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Pereira NL, Rihal C, Lennon R et al (2021) Effect of CYP2C19 genotype on ischemic outcomes during oral P2Y12 inhibitor therapy: a meta-analysis. JACC Cardiovasc Interv 14:739–750

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wang Y, Meng X, Wang A et al (2021) For the CHANCE-2 investigators. Ticagrelor versus clopidogrel in CYP2C19 loss-of-function carriers with stroke or TIA. N Engl J Med 385:2520–2530

    Article  CAS  PubMed  Google Scholar 

  17. Levine GN, Bates ER, Blankenship JC et al (2011) 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: executive summary: a report of the American college of cardiology foundation/american heart association task force on practice guidelines and the society for cardiovascular angiography and interventions. J Am Coll Cardiol 58:e44-122

    Article  PubMed  Google Scholar 

  18. Lawton JS, Tamis-Holland JE, Bangalore S et al (2022) 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American college of cardiology/american heart association joint committee on clinical practice guidelines. Circulation 145:e18–e114

    PubMed  Google Scholar 

  19. Sibbing D, Aradi D, Alexopoulos D et al (2019) Updated expert consensus statement on platelet function and genetic testing for guiding P2Y12 receptor inhibitor treatment in percutaneous coronary intervention. JACC Cardiovasc Interv 12:1521–1537

    Article  PubMed  Google Scholar 

  20. State v Bristol-Myers Squibb Company, (2021) civil No. 14-1-0708-03 DEO. (Haw Cir Ct February 15)

  21. Cavallari LH, Franchi F, Rollini F et al (2018) Clinical implementation of rapid CYP2C19 genotyping to guide antiplatelet therapy after percutaneous coronary intervention. J Translational Med 16:92

    Article  CAS  Google Scholar 

  22. Bergmeijer TO, Vos GJ, Claassens DMF et al (2019) Feasibility and implementation of CYP2C19 genotyping in patients using antiplatelet therapy. Pharmacogenomics 19:621–628

    Article  Google Scholar 

  23. Multi-partner grant awarded for the validation of Genedrive® CYP2C19 ID Kit in time critical NHS settings. http://www.genedriveplc.com/press-releases/gdr_-_devote_(16.06.23).pdf. Accessed 5 Jan 2024

Download references

Funding

This study was funded by Inova Heart and Vascular Institute. 

Author information

Authors and Affiliations

  1. Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, MD, 21215, USA

    Paul A. Gurbel, Kevin Bliden, Juzer Ali Asgar & Udaya S. Tantry

  2. Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Fairfax, VA, USA

    Paul A. Gurbel, Kevin Bliden, Matthew Sherwood, Hamid Taheri, Behnam Tehrani, Marjaneh Akbari, Shahram Yazdani & Udaya S. Tantry

  3. Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Rahul Chaudhary

  4. Artificial Intelligence for Holistic Evaluation and Advancement of Cardiovascular Thrombosis (AI-HEART) Lab, Pittsburgh, PA, USA

    Rahul Chaudhary

Authors
  1. Paul A. Gurbel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kevin Bliden
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Matthew Sherwood
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hamid Taheri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Behnam Tehrani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marjaneh Akbari
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shahram Yazdani
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Juzer Ali Asgar
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Rahul Chaudhary
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Udaya S. Tantry
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul A. Gurbel.

Ethics declarations

Conflict of interest

Dr. Paul A Gurbel, Dr. Gurbel has received consulting fees and/or honoraria from Bayer, Vectura/Otitopic, Janssen, Cleveland Clinic foundation, Wolters Kluwer Pharma, Web MD Medscape, Baron and Budd, Premier Health Care Resource, Baim Institute, and Medforce; institutional research grants from Accriva Diagnostics, AstraZeneca, Bayer, Cronos, Janssen Pharmaceuticals Inc., Haemonetics, Hikari Dx, Idorisa, Labcorp Drug Development, Novartis, Prolocor, Recor Medical, Vectura Limited, Zoll Medical Corporation; in addition, Dr. Gurbel has two patents, Detection of restenosis risk in patients issued and Assessment of cardiac health and thrombotic risk in a patient. Dr. Gurbel was an expert witness in a lawsuit associated with Plavix. Other authors report no relevant disclosures.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gurbel, P.A., Bliden, K., Sherwood, M. et al. Development of a routine bedside CYP2C19 genotype assessment program for antiplatelet therapy guidance in a community hospital catheterization laboratory. J Thromb Thrombolysis 57, 566–575 (2024). https://doi.org/10.1007/s11239-024-02953-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-024-02953-8

Keywords

Search

Navigation