Abstract
Clopidogrel is an antiplatelet drug given to patients before and after having a percutaneous coronary intervention (PCI). Genomic variants in the CYP2C19 gene are associated with variable enzyme activities affecting drug metabolism and hence, patients with reduced or increased enzymatic function have increased risk of bleeding. We conducted a cost-effectiveness analysis to compare a pharmacogenomics versus a non-pharmacogenomics-guided clopidogrel treatment for coronary artery syndrome patients undergoing PCI in the Spanish healthcare setting. A total of 549 patients diagnosed with coronary artery disease followed by PCI were recruited. Dual antiplatelet therapy was administrated to all patients from 1 to 12 months after PCI. Patients were classified into two groups: the Retrospective group was treated with clopidogrel based on the clinical routine practice and the Prospective group were initially genotyped for the presence of CYP2C19 variant alleles before treatment with those carrying more than one CYP2C19 variant alleles given prasugrel treatment. We collected data on established clinical and health outcome measures, including, per treatment arm: the percentage of patients that suffered from (a) myocardial infraction, (b) major bleeding and minor bleeding, (c) stroke, (d) the number of hospitalization days, and (e) the number of days patients spent in Intensive Care Unit. Our primary outcome measure for the cost-effectiveness analysis was Quality Adjusted Life Years (QALYs). To estimate the treatment cost for each patient, individual data on its resource used were combined with unit price data, obtained from Spanish national sources. The analysis predicts a survival of 0.9446 QALYs in the pharmacogenomics arm and 0.9379 QALYs in the non-pharmacogenomics arm within a 1-year horizon. The cumulative costs per patient were €2971 and €3205 for the Prospective and Retrospective groups, respectively. The main cost driver of total cost in both arms was hospitalization costs. The incremental cost-effectiveness ratio (ICER) was negative indicating that the PGx was a dominant option. Our data show that pharmacogenomics-guided clopidogrel treatment strategy may represent a cost-effective choice compared with non-pharmacogenomics-guided strategy for patients undergoing PCI.
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References
Sanchis-Gomar F, Perez-Quilis C, Leischik R, Lucia A. Epidemiology of coronary heart disease and acute coronary syndrome. Ann Transl Med. 2016;4:256.
Pletcher MJ, Moran AE. Cardiovascular risk assessment. Med Clin North Am. 2017;101:673–88.
Wilkins E, Wilson L, Wickramasinghe K, Bhatnagar P, Leal J, Luengo-Fernandez R, et al. European Cardiovascular Disease Statistics 2017. Brussels: European Heart Network; 2017.
O’gara PT, Kushner FG, Ascheim DD, Casey DE, Chung MK, De Lemos JA. et al. American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; American College of Emergency Physicians; Society for Cardiovascular Angiography and Interventions. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the American College of Emergency Physicians and Society for Cardiovascular Angiography and Interventions. Catheter Cardiovasc Interv. 2013;82:E1–27.
Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE, et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2012;60:645–81.
Savi P, Herbert JM, Pflieger AM, Dol F, Delebassee D, Combalbert J, et al. Importance of hepatic metabolism in the antiaggregating activity of the thienopyridine clopidogrel. Biochem Pharmacol. 1992;44:527–32.
Savi P, Pereillo JM, Uzabiaga MF, Combalbert J, Picard C, Maffrand JP, et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost. 2000;84:891–6.
Dean L. Clopidogrel Therapy and CYP2C19 Genotype. In: Pratt V, Mc Leod H Rubinstein W, Dean L, Kattman B, Malheiro A, editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012 [updated 2018 Apr 18].
Huang B, Cui DJ, Ren Y, Han B, Yang DP, Zhao X. Effect of cytochrome P450 2C19*17 allelic variant on cardiovascular and cerebrovascular outcomes in clopidogrel-treated patients: A systematic review and meta-analysis. J Res Med Sci. 2017;22:109.
1000 Genomes | A Deep Catalog of Human Genetic Variation [Online]. Available: http://www.internationalgenome.org/ [Accessed, 2018].
Zhong Z, Hou J, Li B, Zhang Q, Liu S, Li C, et al. Analysis of CYP2C19 genetic polymorphism in a large ethnic hakka population in southern China. Med Sci Monit. 2017;23:6186–92.
Lhermusier T, Waksman R. Prasugrel hydrochloride for the treatment of acute coronary syndromes. Expert Opin Pharmacother. 2015;16:585–96.
Marchini J, Morrow D, Resnic F, Manica A, Kirshenbaum J, Cannon C, et al. An algorithm for use of prasugrel (effient) in patients undergoing cardiac catheterization and percutaneous coronary intervention. Crit Pathw Cardiol. 2010;9:192–8.
EUROSTAT. 2017. Cardiovascular diseases statistics - Statistics Explained [Online]. European Union. Available http://ec.europa.eu/eurostat/statistics-explained/index.php/Cardiovascular_diseases_statistics.
Dávila-Fajardo CL, Sánchez-Ramos J, Villamarín XD, Martínez-González LJ, Frías PT, Huertas SM, et al. The study protocol for a non-randomized controlled clinical trial using a genotype-guided strategy in a dataset of patients who undergone percutaneous coronary intervention with stent. Data Brief. 2017;10:518–24.
Mitropoulou C, Fragoulakis V, Bozina N, Vozikis A, Supe S, Bozina T, et al. Economic evaluation of pharmacogenomic-guided warfarin treatment for elderly Croatian atrial fibrillation patients with ischemic stroke. Pharmacogenomics. 2015;16:137–48.
Mitropoulou C, Fragoulakis V, Rakicevic LB, Novkovic MM, Vozikis A, Matic DM, et al. Economic analysis of pharmacogenomic-guided clopidogrel treatment in Serbian patients with myocardial infarction undergoing primary percutaneous coronary intervention. Pharmacogenomics. 2016;17:1775–84.
Sullivan PW, Arant TW, Ellis SL, Ulrich H. The cost effectiveness of anticoagulation management services for patients with atrial fibrillation and at high risk of stroke in the US. Pharmacoeconomics. 2006;24:1021–33.
Desgagné A, Castilloux AM, Angers JF, Lelorier J. The use of the bootstrap statistical method for the pharmacoeconomic cost analysis of skewed data. Pharmacoeconomics. 1998;13:487–97.
Mizzi C, Dalabira E, Kumuthini J, Dzimiri N, Balogh I, Basak N, et al. A European Spectrum of Pharmacogenomic Biomarkers: Implications for Clinical Pharmacogenomics. PLoS ONE. 2016;11:e0162866.
Brown SA, Pereira N. Pharmacogenomic impact of CYP2C19 variation on clopidogrel therapy in precision cardiovascular medicine. J Pers Med. 2018;8:E8.
Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, et al. Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation. 2009;119:2553–60.
Deiman BA, Tonino PA, Kouhestani K, Schrover CE, Scharnhorst V, Dekker LR, et al. Reduced number of cardiovascular events and increased cost-effectiveness by genotype-guided antiplatelet therapy in patients undergoing percutaneous coronary interventions in the Netherlands. Neth Heart J. 2016;24:589–99.
Kazi DS, Garber AM, Shah RU, Dudley RA, Mell MW, Rhee C, et al. Cost-effectiveness of genotype-guided and dual antiplatelet therapies in acute coronary syndrome. Ann Intern Med. 2014;160:221–32.
Acknowledgements
This work encouraged and coordinated by the Genomic Medicine Alliance Health Economics Working Group. The laboratory of B.R.A. is funded by UAEU grant 31R091.
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Fragoulakis, V., Bartsakoulia, M., Díaz-Villamarín, X. et al. Cost-effectiveness analysis of pharmacogenomics-guided clopidogrel treatment in Spanish patients undergoing percutaneous coronary intervention. Pharmacogenomics J 19, 438–445 (2019). https://doi.org/10.1038/s41397-019-0069-1
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DOI: https://doi.org/10.1038/s41397-019-0069-1