Efficiency of pharmacogenetic approach to anticoagulant therapy in patients with prosthetic heart valves

Background. This study examined clinical, demographic, anthropometric, and inheritance factors that influence individual sensitivity to warfarin therapy after heart valve surgery. The clinical significance of the pharmacogenetic approach was assessed using the individual time frame and time spent in the INR therapeutic range. Aims. We determined the clinical outcome of the pharmacogenetic approach at the start of warfarin therapy in patients with prosthetic heart valves. Materials and methods. The study included 915 patients, of which 512 women and 403 men (mean age 56±10 years), living in Western Siberia. Rheumatic heart disease was the main diagnosis that caused the acquired defect. Mechanical prostheses were used in 70% of cases of cardiac surgery. Real-time polymerase chain reaction used for molecular genetic testing. Results. The frequencies of the alleles and genotypes of CYP2C9 and VKORC1 in the study population of patients with heart valves prosthetic correspond to the distribution in Caucasoid populations. The use of pharmacogenetic testing results at the beginning of warfarin therapy reduced the time required for selecting a therapeutic dose of anticoagulant by 2 times and increased the duration of stay in the INR therapeutic range by 20.2%. Conclusion. The use of the pharmacogenetic approach at the begin‑ ning of warfarin therapy contributes to the effectiveness and safety of anticoagulant therapy in this category of patients.

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27. Wright DFB, Duffull SB. A Bayesian Dose-Individualization Method for Warfarin. Clinical Pharmacokinetics. 2013;52(1):59–68. DOI: 10.1007/s40262-012-0017-6

28. Klein TE, Altman RB, Eriksson N, Gage BF, Kimmel SE, Lee MT et al. Estimation of the Warfarin Dose with Clinical and Pharmacogenetic Data. New England Journal of Medicine. 2009;360(8):753–64. DOI: 10.1056/NEJMoa0809329

29. Kropacheva E.S., Borovkov N.N., Vavilova T.V., Vereina N.K., Vorobyova N.A., Galkina I.S. et al. Fast saturation with warfarin is a predictor of excessive hypocoagulation. Adjusting the algorithm for warfarin dosage. Atherothrombosis. 2015;1:74–86.

30. Sychev D.A., Ivashchenko D.V., Rusin I.V. The impact of pharmacogenetic testing on the risk of bleeding and episodes of excessive hypo coagulation in the use of warfarin: the first meta-analysis of domes tic prospective studies. Therapeutic Archive. 2014;86 (4):64–71.

31. Biswas M, Bendkhale SR, Deshpande SP, Thaker SJ, Kulkarni DV, Bhatia SJ et al. Association between genetic polymorphisms of CYP2C9 and VKORC1 and safety and efficacy of warfarin: Results of a 5 years audit. Indian Heart Journal. 2018;70(Suppl 3):S13–9. DOI: 10.1016/j.ihj.2018.02.005