Comparative clinical and economic evaluation of pharmacogenetic testing application for dabigatran in patients with atrial fibrillation


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Abstract

Aim. To evaluate the clinical and economic feasibility of pharmacogenetic testing (PGT) for dabigataran etexilate administration in the treatment of atrial fibrillation (AF) without valve in comparison with tactics without pharmacogenetic testing. Materials and methods. The pharmacoeconomic model was done using generalized data from published clinical, epidemiological and clinical - economic studies. Results and discussion. Application of PGT on the carrier of allelic variant rs2244613 of CES1 gene for adjustment of dabigatrane etexilate dosage in patients with non - valve AF may be more cost - effective strategy for prevention of thromboembolic complications in patients with non - valve AF. Thus, due to the decrease in the number of undesirable drug reactions in the form of minor and major bleedings, the difference in treatment costs in the group with PGT compared to the group with standard pharmacotherapy tactics per 100 patients was 11 827.65 rubles. The expected cost per patient per year for standard treatment was 36 051.35 rubles, while in the group with PGT it was 35 933.07 rubles. The difference was 1182.76 rubles in favor of the pharmacogenetic approach Conclusion. A PGT approach to correct dabigatrane dosage can reduce the cost of pharmacotherapy by reducing the risk of adverse reactions of minor and major bleeding.

About the authors

Sh P Abdullaev

Russian Medical Academy of Continuous Professional Education

м.н.с. отд. молекулярной медицины НИИ молекулярной и персонализированной медицины; ORCID: 0000-0001-9001-1499 Moscow, Russia

K B Mirzaev

Russian Medical Academy of Continuous Professional Education

Email: karin05doc@yandex.ru
к.м.н., зав. отд. персонализированной медицины НИИ молекулярной и персонализированной медицины; ORCID: 0000-0002-9307-4994 Moscow, Russia

D A Sychev

Russian Medical Academy of Continuous Professional Education

д.м.н., проф., член-корр. РАН, проф. РАН; ректор ФГБОУ ДПО «РМАНПО»; ORCID: 0000-0002-4496-3680 Moscow, Russia

References

  1. https://www.who.int/cardiovascular_diseases/en/ (Ссылка активна на 15.04.2019).
  2. Laslett L.J, Alagona P.Jr, Clark B.A 3rd, Drozda J.P. Jr, Saldivar F, Wilson S.R, Poe C, Hart M. The worldwide environment of cardiovascular disease: prevalence, diagnosis, therapy, and policy issues: a report from the American College of Cardiology. J Am Coll Cardiol. 2012;60(25 Suppl):S1-49. doi: 10.1016/j.jacc.2012.11.002
  3. Kim M.H, Johnston S.S, Chu B.C, et al. Estimation of total incremental health care costs in patients with atrial fibrillation in the United States. Circulation: Cardiovasc Qual Outcom. 2011;4:313-20. doi: 10.1161/CIRCOUTCOMES.110.958165
  4. Patel N.J, Deshmukh A, Pant S, Singh V, Patel N, Arora S, Shah N, Chothani A, Savani G.T, Mehta K, Parikh V, Rathod A, Badheka A.O, Lafferty J, Kowalski M, Mehta J.L, Mitrani R.D, Viles-Gonzalez J.F, Paydak H. Contemporary trends of hospitalization for atrial fibrillation in the United States, 2000 through 2010: implications for healthcare planning. Circulation. 2014;129(23):2371-9. doi: 10.1161/CIRCULATIONAHA.114.008201
  5. Connolly S.J, Ezekowitz M.D, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly P.A, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis B.S, Darius H, Diener H.C, Joyner C.D, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-51. doi: 10.1056/NEJMoa0905561
  6. Shi J, Wang X, Nguyen J.H, Bleske B.E, Liang Y, Liu L, et al. Dabigatran etexilate activation is affected by the CES1 genetic polymorphism G143E (rs71647871) and gender. Biochem Pharmacol. 2016;119:76-84. doi: 10.1016/j.bcp.2016.09.003
  7. Paré G, Eriksson N, Lehr T, Connolly S, Eikelboom J, Ezekowitz M.D, Axelsson T, Haertter S, Oldgren J, Reilly P, Siegbahn A, Syvanen A.C, Wadelius C, Wadelius M, Zimdahl-Gelling H, Yusuf S, Wallentin L. Genetic determinants of dabigatran plasma levels and their relation to bleeding. Circulation. 2013;127:1404-12. doi: 10.1161/CIRCULATIONAHA.112.001233
  8. Dimatteo C, D'Andrea G, Vecchione G, Paoletti O, Cappucci F, Tiscia G.L, Buono M, Grandone E, Testa S, Margaglione M. Pharmacogenetics of dabigatran etexilate interindividual variability. Thromb Res. 2016;144:1-5. doi: 10.1016/j.thromres.2016.05.025
  9. Johnson J.A, Caudle K.E, Gong L, Whirl-Carrillo M, Stein C.M, Scott S.A, Lee M.T, Gage B.F, Kimmel S.E, Perera M.A, Anderson J.L, Pirmohamed M, Klein T.E, Limdi N.A, Cavallari L.H, Wadelius M. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update. Clin Pharm Ther. 2017;102(3):397-404. doi: 10.1002/cpt.668
  10. Ramsey L.B, Johnson S.G, Caudle K.E, Haidar C.E, Voora D, Wilke R.A, Maxwell W.D, Mc Leod H.L, Krauss R.M, Roden D.M, Feng Q, Cooper-De-Hoff R.M, Gong L, Klein T.E, Wadelius M, Niemi M. The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin - induced myopathy: 2014 update. Clin Pharm Ther. 2014;96(4):423-8. doi: 10.1038/clpt.2014.125
  11. Scott S.A, Sangkuhl K, Stein C.M, Hulot J.S, Mega J.L, Roden D.M, Klein T.E, Sabatine M.S, Johnson J.A, Shuldiner A.R; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther. 2013;94(3):317-23. doi: 10.1038/clpt.2013.105
  12. You J.H. Pharmacogenetic - guided selection of warfarin versus novel oral anticoagulants for stroke prevention in patients with atrial fibrillation: a cost - effectiveness analysis. Pharmacogenet Genom. 2014;24(1):6-14. doi: 10.1097/FPC.0000000000000014
  13. Eckman M.H, Rosand J, Greenberg S.M, Gage B.F. Cost - effectiveness of using pharmacogenetic information in warfarin dosing for patients with nonvalvular atrial fibrillation. Ann Intern Med. 2009;150(2):73-83. doi: 10.7326/0003-4819-150-2-200901200-00005
  14. Fragoulakis V, Bartsakoulia M, Díaz-Villamarín X, Chalikiopoulou K, Kehagia K, Ramos J.G.S, Martínez-González L.J, Gkotsi M, Katrali E, Skoufas E, Vozikis A, John A, Ali B.R, Wordsworth S, Dávila-Fajardo C.L, Katsila T, Patrinos G.P, Mitropoulou C. Cost - effectiveness analysis of pharmacogenomics - guided clopidogrel treatment in Spanish patients undergoing percutaneous coronary intervention. Pharmacogenomi J. 2019. [Epub ahead of print]. doi: 10.1038/s41397-019-0069-1
  15. Verbelen M, Weale M.E, Lewis C.M. Cost - effectiveness of pharmacogenetic - guided treatment: are we there yet? Pharmacogenom J. 2017;17(5):395-402. doi: 10.1038/tpj.2017.21
  16. Sychev D.A, Abdullaev S.P, Mirzaev K.B, Ryzhikova K.A, Shuyev G.N, Sozaeva Z.A, Grishina E.A, Mammaev S.N, Gafurov D.M, Kitaeva E.Y, Shprakh V.V, Suleymanov S.S, Bolieva L.Z, Sozaeva M.S, Zhuchkova S.M, Gimaldinova N.E, Sidukova E.E, Asoskova A.V, Mumladze R.B. Genetic determinants of dabigatran safety (CES1 gene rs2244613 polymorphism) in the Russian population: multi - ethnic analysis. Mol Biol Rep. 2019 [Epub ahead of print]. doi: 10.1007/s11033-019-04722-w
  17. Hernandez I, Baik S.H, Piñera A, Zhang Y. Risk of Bleeding With Dabigatran in Atrial Fibrillation. JAMA Intern Med. 2015;175(1):18-24. doi: 10.1001/jamainternmed.2014.5398
  18. Инструкция по медицинскому применению Прадакса®. https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=bb76178c-cf95-4cbd-9883-6ba08ccb508d&t (Ссылка активна на 23.04.2019).
  19. Eikelboom J.W, Wallentin L, Connolly S.J, Ezekowitz M, Healey J.S, Oldgren J, Yang S, Alings M, Kaatz S, Hohnloser S.H, Diener H.C, Franzosi M.G, Huber K, Reilly P, Varrone J, Yusuf S. Risk of bleeding with 2 doses of dabigatran сompared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long - term anticoagulant therapy (RE-LY) trial. Circulation. 2011;123(21):2363-72. doi: 10.1161/CIRCULATIONAHA.110.004747
  20. https://www.medlux.ru/ (Ссылка активна на 15.04.2019).
  21. https://apteka.ru/ (Ссылка активна на 15.04.2019).
  22. Тарифное соглашение на оплату медицинской помощи, оказываемой по территориальной программе обязательного медицинского страхования города Москвы на 2019 год от 27 декабря 2018 года. http://www.mgfoms.ru/medicinskie-organizacii/tarifi (Ссылка активна на 22.04.2019).
  23. Ягудина Р.И., Куликов А.Ю., Метелкин И.А. Методология анализа «затраты - эффективность» при проведении фармакоэкономических исследований. Фармакоэкономика. 2012;4(5):3-8.

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