Pharmacogenetic testing as an element of personalized medicine in real clinical practice


DOI: https://dx.doi.org/10.18565/therapy.2022.4.7-14

Barteneva A.S., Vorobyeva N.A.

1) Northern State Medical University of the Ministry of Healthcare of Russia, Arkhangelsk; 2) Northern branch of National Research Center of Hematology of the Ministry of Healthcare of Russia, Arkhangelsk
Abstract. It has been proven that patients with thrombosis and with a high risk of systemic thromboembolic complications (TEС), including patients with non-valvular atrial fibrillation (AF) should receive effective and safe antithrombotic therapy. A personalized approach to prolonged Vitamin K antagonists (VKA) therapy is associated with an improvement in hemostasiological markers of thrombinemia and clinical outcomes in patients with venous thromboembolism (VTE) and non-valvular AF.
The aim of the study: to evaluate the efficacy and safety of a personalized approach to VKA therapy using pharmacogenetic testing in patients observed at the Regional Center for Antithrombotic Therapy (RCATT) in Arkhangelsk.
Material and methods. Prospective study was carried out on the basis of First City Clinical Hospital named after E.E. Volosevich. The object of the study is patients of the VKA registry who applied to the RCATT (n=107) who underwent pharmacogenetic testing (CYP2C9, CYP4F2, VKORC1 genotype) with calculation of individual doses of warfarin and assessment of quality of life using validated questionnaires. The analysis of the effectiveness and safety of warfarin therapy was carried out.
Results. It was found that complications of warfarin therapy developed regardless of the presence of the genotype (CYP2C9, CYP4F2, VKORC1) and the warfarin dosing algorithm under observation in AC. It has been shown that pharmacogenetic testing in patients with VTE and AF is an additional research method, which is indicated for patients with a hemorrhagic history, frequent minor bleeding at target INR values and the presence of concomitant therapy with cytochrome P450 inhibitors.
Conclusion. Prolonged VKA therapy does not have a significant negative impact on the quality of life under observation in anticoagulant office.

Literature


1. Белоусов Ю.Б., Мареев В.Ю., Явелов И.С., Белоусов Д.Ю. Клинико-экономический анализ эффективности дабигатрана этексилата в сравнении с варфарином в аспекте профилактики сердечно-сосудистых осложнений у пациентов с неклапанной фибрилляцией предсердий. Рациональная фармакотерапия в кардиологии. 2012; 1: 37–44. [Belousov Yu.B., Mareev V.Yu., Yavelov I.S., Belousov D.Yu. Pharmacoeconomic evaluation of dabigatran vs warfarin in cardiovascular events prevention in patients with non-valvular atrial fibrillation. Ratsional’naya farmakoterapiya v kardiologii = Rational Pharmacotherapy in Cardiology. 2012; 1: 37–44 (In Russ.)]. https://dx.doi.org/10.20996/1819-6446-2012-8-1-37-44.


2. Воробьева Н.А., Воробьева А.И., Щапков А.А., Карпунов А.А. Клинико-экономическое обоснование создания системы централизованного лабораторного мониторинга безопасности и эффективности антикоагулянтной терапии в Архангельской области. Лабораторная служба. 2018; 2: 56–62. [Vorobyeva N.A., Vorobyeva A.I., Schapkov A.A., Karpunov A.A. Clinical and economic substantiation of the creation of a system of centralized laboratory monitoring of the safety and efficacy of anticoagulant therapy in the Arkhangelsk region. Laboratornaya sluzhba = Laboratory Service. 2018; 2: 56–62 (In Russ.)]. https://dx.doi.org/10.17116/labs20187256-62.


3. Горбунова Е.В., Седых Д.Ю., Крестова О.С., Брюханова И.А. Эффективность обучающей программы у пациентов с инфарктом миокарда при анализе медико-социальных факторов приверженности к лечению. Сибирский журнал клинической и экспериментальной медицины. 2017; 3: 56–59. [Gorbunova E.V., Sedykh D.Yu., Krestova O.S., Bryukhanova I.A. Efficiency of training program in patients with myocardial infarction in analyzing the medical and social factors of adherence to treatment. Sibirskiy zhurnal klinicheskoy i eksperimental’noy meditsiny = The Siberian Journal of Clinical and Experimental Medicine. 2017; 3: 56–59 (In Russ.)]. https://dx.doi.org/10.29001/2073-8552-2017-32-3-56-59.


4. Кропачева Е.С., Боровков Н.Н., Вавилова Т.В. с соавт. Быстрые темпы насыщения варфарином – предиктор развития чрезмерной гипокоагуляции. Модернизация алгоритма подбора дозы варфарина. Атеротромбоз. 2015; 1: 74–86. [Kropacheva E.S., Borovkov N.N., Vavilova T.V. et al. The rapid rate of saturation with warfarin is a predictor of the development of excessive hypocoagulation. Modernization of the algorithm of warfarin dose selection. Aterotromboz = Atherothrombosis. 2015; 1: 74–86 (In Russ.)]. https://dx.doi.org/10.21518/2307-1109-2015-1-74-86.


5. Шилов А.М., Мельник М.В., Святов И.С. Антикоагулянты непрямого действия в терапевтической практике лечения и профилактики венозного тромбоза. Русский медицинский журнал. 2006; 10: 747. [Shilov A.M., Melnik M.V., Svyatov I.S. Anticoagulants of indirect action in the therapeutic practice of treatment and prevention of venous thrombosis. Russkiy meditsinskiy zhurnal = Russian Medical Journal. 2006; 10: 747 (In Russ.)].


6. Новик А.А., Ионова Т.И. Руководство по исследованию качества жизни в медицине. 2-е изд. Под ред. акад. РАМН Ю.Л. Шевченко. М.: ЗАО «ОЛМА Медиа Групп». 2007; 320 с. [Novik A.A., Ionova T.I. Guidelines for the study of quality of life in medicine. 2nd edition. Ed. by academician of RAMS Shevchenko Yu.L. Moscow: OLMA Media Group. 2007; 320 pp. (In Russ.)]. ISBN: 978-5-373-01011-5.


7. Стойко Ю.М., Кириенко А.И., Затевахин И.И. с соавт. Российские клинические рекомендации по диагностике, лечению и профилактике венозных тромбоэмболических осложнений. Флебология. 2018; 3: 146–240. [Stoyko Yu.M., Kirienko A.I., Zatevakhin I.I. et al. Diagnostics and treatment of chronic venous disease: guidelines of Russian Phlebological Association. Flebologiya = Phlebology. 2018; 3: 146–240 (In Russ.)]. https://dx.doi.org/10.17116/flebo20187031146.


8. Сычев Д.А., Казаков Р.Е., Отделенов В.А., Прокофьев А.Б. Прикладные аспекты применения фармакогенетического тестирования для персонализации применения пероральных антикоагулянтов в российских условиях. Рациональная фармакотерапия в кардиологии. 2013; 5: 525–531. [Sychev D.A., Kazakov R.E., Otdelenov V.A., Prokofiev A.B. Applications of pharmacogenetic testing for personalization of therapy with oral anticoagulants in Russia. Ratsional’naya farmakoterapiya v kardiologii = Rational Pharmacotherapy in Cardiology. 2013; 5: 525–531 (In Russ.)]. https://dx.doi.org/10.20996/1819-6446-2013-9-5-525-531.


9. Ferrari M., Pengo V., Barolo M. et al. Assessing the relative potency of (S)- and (R)-warfarin with a new PK-PD model, in relation to VKORC1 genotypes. Eur J Clin Pharmacol. 2017; 73(6): 699–707. https://dx.doi.org/10.1007/s00228-017-2248-9.


10. Aomori T., Fujita Y., Obayashi K. et al. Case report: dose adjustment of warfarin using genetic information and plasma concentration monitoring. J Clin Pharm Ther. 2014; 39(3): 319–21. https://dx.doi.org/10.1111/jcpt.12135.


11. Clarkesmith D.E., Pattison H.M., Lip G.Y., Lane D.A. Educational intervention improves anticoagulation control in atrial fibrillation patients: the TREAT randomised trial. PLoS One. 2013; 8(9): e74037. https://dx.doi.org/10.1371/journal.pone.0074037.


12. Heit J.A. The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol. 2008; 28(3): 370–72. https://dx.doi.org/10.1161/ATVBAHA.108.162545.


13. Johnson J.A., Gong L., Whirl-Carrillo M. et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin Pharmacol Ther. 2011; 90(4): 625–29. https://dx.doi.org/10.1038/clpt.2011.185.


14. Kim T.H., Kim J.Y., Mun H.S. et al. Heparin bridging in warfarin anticoagulation therapy initiation could increase bleeding in nonvalvular atrial fibrillation patients: A multicenter propensity-matched analysis. J Thromb Haemost. 2015; 13(2): 182–90. https://dx.doi.org/10.1111/jth.12810.


15. Lapner S., Cohen N., Kearon C. Influence of sex on risk of bleeding in anticoagulated patients: A systematic review and meta-analysis. J Thromb Haemost. 2014; 12(5): 595–605. https://dx.doi.org/10.1111/jth.12529.


16. Ware J.E., Kosinski M., Keller S.D. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996; 34(3): 220–33. https://dx.doi.org/10.1097/00005650-199603000-00003.


17. You J.J., Singer D.E., Howard P.A. et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012; 141(2): E531S–E575S. https://dx.doi.org/10.1378/chest.11-2304.


18. 1Zieren J., Zieren H.U., Wenger F., Muller J.M. [Repair of inguinal hernia in the elderly. Results of the plug and patch repair with special reference to quality of life. Chirurg. 2000; 71(5): 564–67 (In German)]. https://dx.doi.org/10.1007/s001040051103.


19. Zigmond A.S., Snaith R.P. The hospital anxiety and depression scale, HADS. Acta Psychiatr Scand. 1983; 67(6): 361–70. https://dx.doi.org/10.1111/j.1600-0447.1983.tb09716.x.


About the Autors


Alexandra S. Barteneva, PhD in Medicine, associate professor of the Department of clinical pharmacology and pharmacotherapy, Northern State Medical University of the Ministry of Healthcare of Russia. Address: 163000, Arkhangelsk, 51 Troitsky Avenue. E-mail: aleksandra10615@gmail.com
Nadezhda A. Vorobyeva, Dr. med. habil., professor, head of the Department of clinical pharmacology and pharmacotherapy, Northern State Medical University of the Ministry of Healthcare of Russia, director of Northern branch of National Research Center of Hematology of the Ministry of Healthcare of Russia. Address: 163000, Arkhangelsk, 51 Troitsky Avenue. E-mail: nadejdav0@gmail.com


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