Relevance. Left ventricular assist device (LVAD) is an alternative treatment for heart failure (HF) patients which improves patient’s quality of life at their end-stage. Despite to the improvement LVAD is beleaguered with thrombosis/bleeding complications in 70% of HF patients after implantation. An anticoagulant treatment of warfarin is usually prescribed to reduce thrombosis complications. However, due to the incorrect dosage of the treatment thrombosis/ bleeding complications still happen. Warfarin dose could be identified by genetic variants of vitamin K-epoxide reductase complex (VKORC1) and the cytochrome P450-2C9 (CYP2C9) which account for 50% of dose variability. Aim. The aim of our investigation is to identify variability of warfarin dose according to the genotype polymorphisms of genes and their difference from the clinical dosage in HF patients. Materials and methods. The case series study included 98 HF patients (without complications – 74 patients, with complications – 24 patients) with prescribed warfarin treatment after device implantation. Clinical warfarin dosage difference was identified between genotype polymorphisms of rs9923231, rs9934438 in VKORC1 gene. Furthermore, warfarin dosage was calculated according to the genetic test results and compared with clinical dosage. Results. Warfarin dosage according to the clinical protocol between three genotypes of polymorphisms in VKORC1 gene showed significant difference. HF patients were prescribed with higher warfarin dosage with wild type genotype polymorphism of rs9934438 in VKORC1 gene than with mutant genotype < 2.5mg (3.88 ± 1.25 vs. 2.44 ± 0.81, p = 0.00005). Conclusion. Genotype-guided warfarin dosing may estimate accurate dose and potentially improve outcomes in LVAD patients.
Madina R. Zhalbinova1,2, Saule E. Rakhimova1, Saltanat A. Andosova3, Gulbanu A. Akilzhanova4, Makhabbat S. Bekbosynova3, Ainur R. Akilzhanova1,2, 1 National Laboratory Astana, Nazarbayev University, Astana, the Republic of Kazakhstan; 2 L.N. Gumilyov Eurasian National University, Astana, the Republic of Kazakhstan; 3 National Research Cardiac Surgery Center, Astana, the Republic of Kazakhstan; 4 Pavlodar branch of NCJSC «Semey Medical University», Pavlodar, the Republic of Kazakhstan.
1. Al-Eitan L.N., Almasri A.Y., Khasawneh R.H. Effects of CYP2C9 and VKORC1 polymorphisms on warfarin sensitivity and responsiveness during the stabilization phase of therapy // Saudi Pharm J. 2019. 27 (4). P. 484-490. 2. Alrashid M.H., Al-Serri A., Alshemmari S.H., Koshi P., Al-Bustan S.A. Association of Genetic Polymorphisms in the VKORC1 and CYP2C9 Genes with Warfarin Dosage in a Group of Kuwaiti Individuals // Mol Diagn Ther. 2016. 20 (2). P. 183-90. 3. Awad M., Czer L.S., Soliman C., et al. Prevalence of Warfarin Genotype Polymorphisms in Patients with Mechanical Circulatory Support // ASAIO J. 2015. 61 (4). P. 391-6. 4. Berardi C., Bravo C.A., Li S., Khorsandi M., et al. The History of Durable Left Ventricular Assist Devices and Comparison of Outcomes: HeartWare, HeartMate II, HeartMate 3, and the Future of Mechanical Circulatory Support // J Clin Med. 2022. 11 (7). 5. Boehme A.K., Pamboukian S.V., George J.F., Beasley T.M., et al. Anticoagulation Control in Patients With Ventricular Assist Devices // ASAIO J. 2017. 63 (6). P. 759-765. 6. Chen Z., Zhang J., Kareem K., Tran D., Conway R.G., Arias K., Griffith B.P., Wu Z.J. Device-induced platelet dysfunction in mechanically assisted circulation increases the risks of thrombosis and bleeding // Artif Organs. 2019. 43(8). P. 745-755. 7. Deconinck S.J., Nix C., Barth S., Bennek-Schopping E., Rauch A., Schelpe A.S., Roose E., et al. ADAMTS13 inhibition to treat acquired von Willebrand syndrome during mechanical circulatory support device implantation // J Thromb Haemost. 2022. 20 (12). P. 2797-2809. 8. Feher G., Feher A., Pusch G., Lupkovics G., Szapary L., Papp E. The genetics of antiplatelet drug resistance // Clin Genet. 2009. 75 (1). P. 1-18. 9. Finkelman B.S., Gage B.F., Johnson J.A., Brensinger C.M., Kimmel S.E. Genetic warfarin dosing: tables versus algorithms // J Am Coll Cardiol. 2011. 57 (5). P. 612-618. 10. Johnson J.A., Gong L., Whirl-Carrillo M., Gage B. F., Scott S.A., Stein C.M., Anderson J.L., Kimmel S.E., Lee M.T., Pirmohamed M., Wadelius M., Klein T.E., Altman R.B. Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing // Clin Pharmacol Ther. 2011. 90 (4). P. 625-629. 11. Kadakia S., Moore R., Ambur V., Toyoda Y. Current status of the implantable LVAD // Gen Thorac Cardiovasc Surg. 2016. 64(9). P. 501-508. 12. Koliopoulou A., McKellar S.H., Rondina M., Selzman C.H. Bleeding and thrombosis in chronic ventricular assist device therapy: focus on platelets // Curr Opin Cardiol. 2016. 31(3). P. 299-307. 13. Dean L. Warfarin Therapy and VKORC1 and CYP Genotype // Medical Genetics Summaries. 2018. P. 1-18. 14. Mehra M.R., Crandall D.L., Gustafsson F., Jorde U.P., Katz J.N., Netuka I., et al. Aspirin and left ventricular assist devices: rationale and design for the international randomized, placebo-controlled, non-inferiority ARIES HM3 trial // Eur J Heart Fail. 2021. 23 (7). P. 1226-1237. 15. Nakagita K., Wada K., Mukai Y., Uno T., Nishino R., Matsuda S., Takenaka H., Terakawa N., Oita A., Takada M. Effects of vitamin K epoxide reductase complex 1 gene polymorphisms on warfarin control in Japanese patients with left ventricular assist devices (LVAD) // Eur J Clin Pharmacol. 2018. 74 (7). P. 885-894. 16. Perera M.A., Cavallari L.H., Limdi N.A., Gamazon E.R., Konkashbaev A., Daneshjou R., Pluzhnikov A., Crawford D.C., Wang J., Liu N., Tatonetti N. et al. Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study // The Lancet. 2013. 382 (9894). P. 790-796. 17. Scott S.A., Khasawneh R., Peter I., Kornreich R., Desnick R.J. Combined CYP2C9, VKORC1 and CYP4F2 frequencies among racial and ethnic groups // Pharmacogenomics. 2010. 11 (6). P. 781-91. 18. Topkara V.K., Knotts R.J., Jennings D.L., Garan A.R., Levin A.P., et al. Effect of CYP2C9 and VKORC1 Gene Variants on Warfarin Response in Patients with Continuous-Flow Left Ventricular Assist Devices // ASAIO J. 2016. 62 (5). P. 558-564. 19. Wadelius M., Chen L. Y., Eriksson N., Bumpstead S., Ghori J., Wadelius C., Bentley D., Mcginnis R., Deloukas P. Association of warfarin dose with genes involved in its action and metabolism // Hum Genet. 2007. 121 (1). P. 23-34. 20. Würtz M., Kristensen S.D., Hvas A.M., Grove E. L. Pharmacogenetics of the Antiplatelet Effect of Aspirin // Current Pharmaceutical Design. 2012. 18 (33). P. 5294-5308. 21. Zhalbinova M.R., Rakhimova S.E., Kozhamkulov U.A., Akilzhanova G.A., Kaussova G.K., Akilzhanov K.R., Pya Y.V., Lee J.H., Bekbossynova M.S., Akilzhanova A.R. Association of Genetic Polymorphisms with Complications of Implanted LVAD Devices in Patients with Congestive Heart Failure: A Kazakhstani Study // J Pers Med. 2022. 12 (5).
Количество просмотров: 98

Ключевые слова:

Библиографическая ссылка

Zhalbinova M.R., Rakhimova S.E., Andosova S.A., Akilzhanova G.A., Bekbosynova M.S., Akilzhanova A.R. Estimation of the warfarin dose in heart failure patients with implanted mechanical circulatory support device // Nauka i Zdravookhranenie [Science & Healthcare]. 2023, (Vol.25) 1, pp. 59-66. doi 10.34689/SH.2023.25.1.007

Авторизируйтесь для отправки комментариев