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Cost Effectiveness of a CYP2C19 Genotype-Guided Strategy in Patients with Acute Myocardial Infarction: Results from the POPular Genetics Trial

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Abstract

Introduction

The POPular Genetics trial demonstrated that a CYP2C19 genotype-guided P2Y12 inhibitor strategy reduced bleeding rates compared with standard treatment with ticagrelor or prasugrel without increasing thrombotic event rates after primary percutaneous coronary intervention (PCI).

Objective

In this analysis, we aimed to evaluate the cost effectiveness of a genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel.

Methods

A 1-year decision tree based on the POPular Genetics trial in combination with a lifelong Markov model was developed to compare costs and quality-adjusted life-years (QALYs) between a genotype-guided and a standard P2Y12 inhibitor strategy in patients with myocardial infarction undergoing primary PCI. The cost-effectiveness analysis was conducted from a Dutch healthcare system perspective. Within-trial survival and utility data were combined with lifetime projections to evaluate lifetime cost effectiveness for a cohort of 1000 patients. Costs and utilities were discounted at 4 and 1.5%, respectively, according to Dutch guidelines for health economic studies. Besides deterministic and probabilistic sensitivity analyses, several scenario analyses were also conducted (different time horizons, different discount rates, equal prices for P2Y12 inhibitors, and equal distribution of thrombotic events between the two strategies).

Results

Base-case analysis with a hypothetical cohort of 1000 subjects demonstrated 8.98 QALYs gained and €725,550.69 in cost savings for the genotype-guided strategy (dominant). The deterministic and probabilistic sensitivity analysis confirmed the robustness of the model and the cost-effectiveness results. In scenario analyses, the genotype-guided strategy remained dominant.

Conclusion

In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel resulted in QALYs gained and cost savings.

Trial Registration

Clinicaltrials.gov number: NCT01761786, Netherlands trial register number: NL2872

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Author information

Author notes

  1. Pim W. M. van Dorst, Gerrit J. A. Vos have contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, St. Antonius Hospital, Koekoekslaan 1, 3435CM, Nieuwegein, The Netherlands

    Daniel M. F. Claassens, Gerrit J. A. Vos, Thomas O. Bergmeijer & Jurriën M. ten Berg

  2. Department of Cardiology, Isala Hospital, Zwolle, The Netherlands

    Daniel M. F. Claassens & Renicus S. Hermanides

  3. Unit of Global Health, Department of Health Sciences, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Pim W. M. van Dorst, Maarten J. Postma & Cornelis Boersma

  4. Department of Cardiology, University Medical Center Maastricht, Maastricht, The Netherlands

    Arnoud W. J. van ’t Hof

  5. Department of Cardiology, Zuyderland Medical Center, Heerlen, The Netherlands

    Arnoud W. J. van ’t Hof

  6. Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands

    Arnoud W. J. van ’t Hof & Jurriën M. ten Berg

  7. Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands

    Pim van der Harst

  8. Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

    Pim van der Harst & Folkert W. Asselbergs

  9. Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy

    Emanuele Barbato & Carmine Morisco

  10. Cardiovascular Research Center, Onze lieve Vrouwe Hospital, Aalst, Belgium

    Emanuele Barbato

  11. Department of Cardiology, Rijnstate Hospital, Arnhem, The Netherlands

    Richard M. Tjon Joe Gin

  12. Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK

    Folkert W. Asselbergs

  13. Health Data Research UK and Institute of Health Informatics, University College London, London, UK

    Folkert W. Asselbergs

  14. Department of Cardiology, Meander Medical Center, Amersfoort, The Netherlands

    Arend Mosterd

  15. Department of Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands

    Jean-Paul R. Herrman

  16. Department of Cardiology, Amphia Hospital, Breda, The Netherlands

    Willem J. M. Dewilde

  17. Department of Cardiology, Imelda Hospital, Bonheiden, Belgium

    Willem J. M. Dewilde

  18. Department of Pharmacy, University of Groningen, Groningen, The Netherlands

    Maarten J. Postma

  19. Department of Economics, Econometrics and Finance, Faculty of Economics and Business, University of Groningen, Groningen, The Netherlands

    Maarten J. Postma

  20. Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

    Vera H. M. Deneer

  21. Division Laboratories, Pharmacy and Biomedical Genetics, Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands

    Vera H. M. Deneer

  22. Faculty of Management Sciences, Open University, Heerlen, The Netherlands

    Cornelis Boersma

Authors
  1. Daniel M. F. Claassens
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  2. Pim W. M. van Dorst
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  3. Gerrit J. A. Vos
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  4. Thomas O. Bergmeijer
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  6. Arnoud W. J. van ’t Hof
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  14. Willem J. M. Dewilde
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  17. Jurriën M. ten Berg
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  18. Cornelis Boersma
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Corresponding author

Correspondence to Jurriën M. ten Berg.

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Funding

This work was supported by ZonMw, a Dutch government agency, as part of its efficiency research program (project 171102022). Spartan Bioscience (Nepean, Ottawa, ON, Canada) provided the Spartan RX system and the reagents used free of charge.

Conflicts of interest

Dr. Asselbergs has received grants from the University College London Hospitals National Institute for Health Research Biomedical Research Centre. Dr. van 't Hof has received institutional grants from Medtronic, AstraZeneca, and Sanofi and personal fees from AstraZeneca and Amgen. Dr. Barbato has received personal fees from Boston Scientific, Abbott Vascular, and GE. Dr. Ten Berg has received institutional grants from AstraZeneca and ZonMw and personal fees from AstraZeneca, Daiichi Sankyo, Eli Lilly, the Medicines Company, Accumetrics, Boehringer-Ingelheim, Bayer, BMS, Pfizer, and Ferrer. Dr. Postma has received institutional grants from AstraZeneca, GSK, Pfizer, and Amgen and personal fees from AstraZeneca, Daiichi Sankyo, Boehringer-Ingelheim, Bayer, BMS, Pfizer, GSK, and Roche. Daniel M.F. Claassens, Pim W.M. van Dorst, Gerrit J.A. Vos, Thomas O. Bergmeijer, Renicus S. Hermanides, Pim van der Harst, Carmine Morisco, Richard M. Tjon Joe Gin, Arend Mosterd, Jean-Paul R. Herrman, Willem J.M. Dewilde, Vera H.M. Deneer, and Cornelis Boersma have no conflicts of interest that are directly relevant to the content of this article.

Availability of data and material

Data will be made available upon reasonable request

Code availability

Analyses were performed using R version 3.6 or later and Excel.

Ethics approval

An institutional review board at each site approved the trial.

Consent to participate

All patients provided informed consent to participate in the trial.

Author contributions

Conceptualization: TOB, JMtB, VHMD. Methodology: DMFC, WMvD, CB. Formal analysis and investigation: DMFC, WMvD, TOB, GJAV. Writing—original draft preparation: DMFC, WMvD. Writing—review and editing: GJAV, TOB, RSH, AWJv’tH, PvdH, EB, CM, RMTJG, FWA, AM, JPRH, WJMD, MJP. Funding acquisition: VHMD. Resources: RSH, AWJv’tH, PvdH, EB, CM, RMTJG, FWA, AM, JPRH, WJMD. Supervision: VHMD, JMtB, CB, MJP.

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Claassens, D.M.F., van Dorst, P.W.M., Vos, G.J.A. et al. Cost Effectiveness of a CYP2C19 Genotype-Guided Strategy in Patients with Acute Myocardial Infarction: Results from the POPular Genetics Trial. Am J Cardiovasc Drugs 22, 195–206 (2022). https://doi.org/10.1007/s40256-021-00496-4

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