Treatment Adherence as a New Choice Factor for Optimization of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation and Hemostatic Gene Polymorphisms
https://doi.org/10.20996/1819-6446-2016-12-5-494-502
Abstract
Aim. To evaluate treatment adherence and prevalence of CYP2C9 and VKORC1 gene mutations in patients with atrial fibrillation (AF) and provide rationale of choice for oral anticoagulation therapy.
Material and methods. Treatment adherence was evaluated in 137 AF patients (aged 35-85 years) with quantitative estimation of drug therapy adherence along with compliance to medical support and lifestyle modifications. Among them 82 patients underwent polymerase chain reaction (PCR) analysis of CYP2C9 and VKORC1 gene polymorphisms.
Results. Patients receiving anticoagulation therapy are characterized by lower level of adherence compared to patients without anticoagulants (65.2±19.3% vs 68.5±19.1%; Wald-Wolfowitz; p<0.05). Considering all studied parameters men are less adherent than women (54.7±18.6% vs 60.6±16.7%; Kolmogorov-Smirnov; p<0.05). Patients receiving new oral anticoagulants (NOAC) have better compliance compared with patients of warfarin group. Mutations in CYP2C9 gene were detected in 32.9%, VKORC1 – in 68.3%, and their combination – in 21.9% of study participants. Warfarin therapy may be potentially dangerous in such patients due to low adherence.
Conclusion. Considering high prevalence of CYP2C9 and VKORC1 gene mutations treatment adherence should be estimated to optimize choice of anticoagulation therapy. NOAC treatment should be considered in patients with low adherence for prevention of thromboembolic complications.
About the Authors
Yu. P. SkirdenkoRussian Federation
MD, Teaching Assistant, Chair of Faculty Therapy and Occupational Diseases, Omsk State Medical University
A. V. Shustov
Russian Federation
MD, cardiologist, Head of the Cardiology Department, Omsk Regional Clinical Cardiology Dispensary
V. V. Zherebilov
Russian Federation
Teaching Assistant, Chair of Faculty Therapy and Occupational Diseases, Omsk State Medical University
N. A. Nikolayev
Russian Federation
MD, Ph.D., Associate Professor, Chair of Faculty Therapy and Occupational Diseases, Omsk State Medical University
References
1. Wolf P, Abbott R, Kannel W. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991; 22(8): 983–8. doi: 10.1161/01.STR.22.8.983
2. Paul P, Dobesh, Fanikos J. Direct Oral Anticoagulants for the Prevention of Stroke in Patients with Nonvalvular Atrial Fibrillation: Understanding Differences and Similarities. Drugs. 2015; 75(14): 1627–1644. doi: 10.1007/s40265-015-0452-4.
3. Poopak B, Rabieipoor S, Safari N, et al. Identification of CYP2C9 and VKORC1 polymorphisms in Iranian patients who are under warfarin therapy. Int J Hematol Oncol Stem Cell Res. 2015;9(4): 185–92.
4. Fung E, Patsopoulos NA, Belknap SM, et al. Effect of genetic variants, especially CYP2C9 and VKORC1, on the pharmacology of warfarin. Thromb Hemost. 2012; 38(8): 893–904. doi: 10.1055/s-0032-1328891.
5. Militaru FC, Vesa SC, Pop TR, et al. Pharmacogenetics aspects of oral anticoagulants therapy. J Med Life. 2015; 8(2): 171–5.
6. Carukjan AA. The prevalence of polymorphic variants of CYP2C9 * 2 and CYP2C9 * 3 gene cytochrome CYP2C9 residents of Stavropol Territory. Materials of the II inter-regional scientific-practical conference of young scientists and specialists "Medical science: a look into the future." Stavropol': StGMU; 2014. P. 108-13. (In Russian) [Царукян А. А. Распространенность полиморфных вариантов CYP2C9*2 и CYP2C9*3 гена цитохрома CYP2C9 у жителей Ставропольского края. Материалы II межрегиональной научно- практической конференции молодых ученых и специалистов «Медицинская наука: взгляд в будущее». Ставрополь: СтГМУ; 2014. С. 108-13].
7. Sirotkina OV, Ulitina AS, Taraskina AE, et al. Allelic variants CYP2C9 * 2 and CYP2C9 * 3 cytochrome CYP2C9 gene in the population of St. Petersburg and their clinical significance in anticoagulation therapy with warfarin. Rossijskij Kardiologicheskij Zhurnal 2004; (6): 47- 50. (In Russian) [Сироткина О.В., Улитина А.С., Тараскина А.Е. и соавт. Аллельные варианты CYP2C9*2 и CYP2C9*3 гена цитохрома CYP2C9 в популяции Санкт-петербурга и их клиническое значение при антикоагулянтной терапии варфарином. Российский Кардиологический Журнал 2004; (6): 47-50].
8. Nikolaev N.A. Prognosis of adherence to a constant drug therapy in participant of clinical trial. In: Nikolaev N.A., ed. Manual of clinical examination in internal medicine. Moscow: Izdatel'skij dom Akademii Estestvoznanija; 2015. (In Russian) [Николаев Н.А. Прогноз приверженности участника клинического исследования к постоянной лекарственной терапии. В: Николаев Н.А., ред. Руководство по клиническим исследованиям внутренних болезней. М.: Издательский дом Академии Естествознания; 2015].
Review
For citations:
Skirdenko Yu.P., Shustov A.V., Zherebilov V.V., Nikolayev N.A. Treatment Adherence as a New Choice Factor for Optimization of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation and Hemostatic Gene Polymorphisms. Rational Pharmacotherapy in Cardiology. 2016;12(5):494-502. https://doi.org/10.20996/1819-6446-2016-12-5-494-502