Ways to increase freedom from DOAC-dependent complications in elderly patients with polypharmacy and chronic kidney disease: molecular and genetic aspects

Мұқаба
  • Авторлар: Kondrakhin A.P.1,2, Silina E.G.3, Chernyaeva M.S.2,4, Maksimov M.L.1,5, Belokopytov A.S.1, Babichev A.N.1, Smirnova Y.E.1, Martynova S.A.1, Shnaider K.O.1,5
  • Мекемелер:
    1. Federal State Autonomous Educational Institution of Higher Education “Russian National Research Medical University named after N.I. Pirogov” of the Ministry of Health of the Russian Federation
    2. Moscow State Budgetary Healthcare Institution “Hospital for War Veterans No.2 of the Moscow City Healthcare Department”
    3. Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of The Ministry of Health of the Russian Federation
    4. Federal State Budgetary Institution of Continuing Professional Education “Central State Medical Academy” of the Administrative Department of the President of the Russian Federation
    5. Federal State Budgetary Educational Institution of Additional Professional Education “Russian Medical Academy of Continuous Professional Education”, Ministry of Health of Russia
  • Шығарылым: Том 23, № 3 (2025)
  • Беттер: 39-47
  • Бөлім: Original research
  • URL: https://journals.rcsi.science/1728-2918/article/view/312097
  • DOI: https://doi.org/10.29296/24999490-2025-03-05
  • ID: 312097

Дәйексөз келтіру

Толық мәтін

Ашық рұқсат Ашық рұқсат
Рұқсат жабық Рұқсат берілді
Рұқсат жабық Тек жазылушылар үшін

Аннотация

Introduction. Thanks to advances in modern medicine, it has been possible to significantly increase life expectancy. With the high effectiveness of methods for diagnosing and treating many chronic pathologies, a sharp increase in the number of elderly patients is expected. This cohort of patients has features including polymorbidity; polypharmacy, and low compliance. Taking direct oral anticoagulants (DOACs) is associated with a risk of hemorrhagic complications, which can be difficult to predict in elderly patients, especially those with impaired renal function.

Objective. To evaluate factors that increase the risk of taking direct oral anticoagulants in elderly patients with polypharmacy and chronic kidney disease based on the analysis of molecular and genetic markers.

Material and methods. For this study, a database was collected that included 503 patients observed at the Moscow State Budgetary Healthcare Institution “Hospital for War Veterans No.2 of the Moscow City Healthcare Department” for the period from April to September 2023 with atrial fibrillation and stage 2C–4C kidney disease. The questionnaire method was used, as well as the collection of clinical and laboratory data to evaluate DOAC-dependent complications – cases of bleeding, duration of DOAC administration. Additionally, molecular markers of endothelial dysfunction and inflammation were determined, as well as genetic polymorphisms associated with DOAC metabolism in kidney tissues.

Results. DOAC administration increases bleeding risks with a significant decrease in creatinine clearance (less than 45 ml/min/1.73m2), especially with dabigatran. This observation regarding dabigatran applied to patients in CKD stages C2 and C3a; with creatinine clearance less than 45 ml/min/1.73 m2, this drug was rarely used. The use of apixaban and rivaroxaban does not have a statistically significant increase in the incidence of hemorrhagic complications as renal failure progresses. A correlation was found between the level of molecular markers of endothelial dysfunction (eNOS, VEGF) and the risk of developing DOAC-dependent bleeding. Patients with the rs2032582 single nucleotide polymorphism of the ABCB1 (MDR1) gene had an increased risk of hemorrhagic complications when taking dabigatran.

Conclusion. The study of drug interactions and the association of DOAC intake with various endpoints in larger samples will help identify molecular and genetic predictors of adverse outcomes and adjust therapy. A personalized approach to DOAC prescription based on the assessment of kidney function, molecular markers of endothelial dysfunction, and the patient's genetic profile can significantly reduce the risk of hemorrhagic complications in geriatric patients.

Толық мәтін

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Авторлар туралы

Andrey Kondrakhin

Federal State Autonomous Educational Institution of Higher Education “Russian National Research Medical University named after N.I. Pirogov” of the Ministry of Health of the Russian Federation; Moscow State Budgetary Healthcare Institution “Hospital for War Veterans No.2 of the Moscow City Healthcare Department”

Хат алмасуға жауапты Автор.
Email: 79104851199@yandex.ru
ORCID iD: 0000-0002-3439-8059
SPIN-код: 1402-2947

Candidate of Medical Sciences, Senior Lecturer, Pharmacology Department, Institute of Pharmacy and Medical Chemistry, Chief Specialist, Clinical Pharmacology, South-Eastern Administrative District, Moscow Health Department, Clinical Pharmacologist

Ресей, Ostrovityanova str., 1, Moscow, 117997; Volgogradskiy Prospekt, 168, Moscow, 109472

Elena Silina

Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of The Ministry of Health of the Russian Federation

Email: elena.siline@gmail.com
ORCID iD: 0000-0003-0406-3888
SPIN-код: 2245-4442

Candidate of Medical Sciences, Associate Professor, Department of Therapy, Clinical Pharmacology and Emergency Medical Care

Ресей, Dolgorukovskaya st., 4, Moscow, 127006

Marina Chernyaeva

Moscow State Budgetary Healthcare Institution “Hospital for War Veterans No.2 of the Moscow City Healthcare Department”; Federal State Budgetary Institution of Continuing Professional Education “Central State Medical Academy” of the Administrative Department of the President of the Russian Federation

Email: doctor@cherniaeva.ru
ORCID iD: 0000-0003-3091-7904
SPIN-код: 2244-0320

Candidate of Medical Sciences, Head of the Geriatric Department, Associate Professor at the Department of Internal Diseases and Preventive Medicine, Chief Freelance Geriatrician of the South-Eastern Administrative District of Moscow

Ресей, Volgogradskiy Prospekt, 168, Moscow, 109472; Marshal Timoshenko St., 19, build. 1A, Moscow, 121359

Maksim Maksimov

Federal State Autonomous Educational Institution of Higher Education “Russian National Research Medical University named after N.I. Pirogov” of the Ministry of Health of the Russian Federation; Federal State Budgetary Educational Institution of Additional Professional Education “Russian Medical Academy of Continuous Professional Education”, Ministry of Health of Russia

Email: maksim_maksimov@mail.ru
ORCID iD: 0000-0002-8979-8084
SPIN-код: 6261-3982

Professor, Department of Pharmacology, Institute of Pharmacy and Medical Chemistry, Head, Department of Clinical Pharmacology and Pharmacotherapy, Kazan State Medical Academy, Dean, Faculty of Preventive Medicine and Healthcare Organization, Doctor of Medical Sciences, Professor

Ресей, Ostrovityanova str., 1, Moscow, 117997; Barrikadnaya st., 2/1, Moscow, 125993

Arkhip Belokopytov

Federal State Autonomous Educational Institution of Higher Education “Russian National Research Medical University named after N.I. Pirogov” of the Ministry of Health of the Russian Federation

Email: arhip1501@gmail.com
ORCID iD: 0009-0008-1746-2611

3rd year student, Institute of Clinical Medicine

Ресей, Ostrovityanova str., 1, Moscow, 117997

Artem Babichev

Federal State Autonomous Educational Institution of Higher Education “Russian National Research Medical University named after N.I. Pirogov” of the Ministry of Health of the Russian Federation

Email: brain000storm@gmail.com
ORCID iD: 0009-0001-4826-3411

3rd year student of the Institute of Clinical Medicine

Ресей, Ostrovityanova str., 1, Moscow, 117997

Yulia Smirnova

Federal State Autonomous Educational Institution of Higher Education “Russian National Research Medical University named after N.I. Pirogov” of the Ministry of Health of the Russian Federation

Email: yuliya18_04@mail.ru
ORCID iD: 0009-0002-1358-6752

4th year student of the Institute of Maternity and Childhood

Ресей, Ostrovityanova str., 1, Moscow, 117997

Sofya Martynova

Federal State Autonomous Educational Institution of Higher Education “Russian National Research Medical University named after N.I. Pirogov” of the Ministry of Health of the Russian Federation

Email: sofya.martynova2014@yandex.ru
ORCID iD: 0009-0000-0343-0848

4th year student of the Institute of Maternity and Childhood

Ресей, Ostrovityanova str., 1, Moscow, 117997

Ksenia Shnaider

Federal State Autonomous Educational Institution of Higher Education “Russian National Research Medical University named after N.I. Pirogov” of the Ministry of Health of the Russian Federation; Federal State Budgetary Educational Institution of Additional Professional Education “Russian Medical Academy of Continuous Professional Education”, Ministry of Health of Russia

Email: ks.shnaider@mail.ru
ORCID iD: 0000-0002-0630-4238
SPIN-код: 9979-2700

Assistant of the Department of Pharmacology, Institute of Pharmacy and Medical Chemistry, Assistant of the Department of Pharmacy, General Pharmacology and Pharmaceutical Consulting

Ресей, Ostrovityanova str., 1, Moscow, 117997; Barrikadnaya st., 2/1, Moscow, 125993

Әдебиет тізімі

  1. Максимов М.Л., Бонцевич Р.А., Бурашникова И.С. и др. Клиническая фармакология и рациональная фармакотерапия для практикующих врачей: учебник. Под ред. проф. М.Л. Максимова. Казань: ИД «МеДДоК», 2021; 948. [Maksimov M.L., Bontsevich R.A., Burashnikova I.S. and others. Clinical pharmacology and rational pharmacotherapy for practicing physicians: textbook. Edited by prof. M.L. Maksimov. Kazan: Publishing house "Meddock", 2021; 948 (in Russian).]
  2. Gallagher P., Ryan C., Byrne S. et al. STOPP (Screening Tool of Older Person's Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment). Consensus validation. Int J Clin Pharmacol Ther. 2008; 46 (2): 72–83. doi: 10.5414/CPP46072.
  3. Machado-Duque M.E., Castaño-Montoya J.P., MedinaMorales D.A., et al. Drugs with Anticholinergic Potential and Risk of Falls with Hip Fracture in the Elderly Patients: A Case-Control Study. J. Geriatr Psychiatry Neurol. 2018; 31 (2): 63–9. DOI: https://doi.org/10.1016/j.rcp.2020.11.004
  4. Кузьмин О.Б. Хроническая болезнь почек: механизмы развития и прогрессирования гипоксического гломерулосклероза и тубулоинтерстициального фиброза. Нефрология. 2015; 19 (4): 6–16. [Kuzmin O.B. Chronic kidney disease: mechanisms of hypoxic glomerulosclerosis and tubulointerstitial fibrosis development and progression. Nephrology (Saint-Petersburg). 2015; 19 (4): 6–16 (In Russ.)]
  5. Hanlon J.T., Handler S.M., Maher R.L., Schmader K.E. Geriatric Pharmacotherapy and Polypharmacy. In: Fillit H.M., Rockwood K., Young J.B. Brocklehurst's Textbook of Geriatric Medicine and Gerontology. 8th ed. Elsevier 2017; 849–54.
  6. Leelakanok N., Holcombe A.L, Lund B.C., et al. Association between polypharmacy and death: A systematic review and meta-analysis. J. Am. Pharm Assoc. 2017; 57 (6): 729–38. DOI: https://doi.org/10.1016/j.japh.2017.06.002
  7. Baruth J.M., Gentry M.T., Rummans T.A. et al. Multidisciplinary Guideline for Polypharmacy in older people. Hosp Pract (1995). 2020; 48 (sup1): 56–62. DOI: https://doi.org/10.1080/21548331.2019.1706995
  8. Смирнов А.В., Волков М.М. Роль витамина D в замедлении прогрессирования хронической болезни почек. Нефрология. 2008; 12 (4): 7–13. [Smirnov A.V., Volkov M.M. Role of vitamin D in slowing the progression of chronic kidney disease. Nephrology. 2008; 12 (4): 7–13 (In Russ.)]
  9. Лисянская О.Ю. Гипоксия – ведущий фактор прогрессирования хронической болезни почек. Нефрология. 2016; 20 (1): 9–15. [Lisyanskaya O.Yu. Hypoxia – the leading factor in the progression of chronic kidney disease. Nephrology. 2016; 20 (1): 9–15 (In Russ.)]
  10. Paré G., Eriksson N., Lehr T., et al. Genetic determinants of dabigatran plasma levels and their relation to bleeding. Circulation. 2013; 127 (13): 1404–12. doi: 10.1161/CIRCULATIONAHA.112.001233
  11. Тайц Б.М. «10П медицина» в решении вопросов снижения смертности, увеличения продолжительности и повышения качества жизни пожилого населения. Клиническая геронтология. 2021; 27 (11–12): 76–9. [Tayts BM. «P10 Medicine» for lower mortality, longer life expectancy and better quality of life in elderly people. Clin Gerontol. 2021; 27 (11–12): 76–9 (in Russian)]

Қосымша файлдар

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Әрекет
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2. Fig. 1. Structure of complications associated with DOAC intake

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3. Fig. 2. Number of drugs taken

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4. Fig. 3. Distribution of patients by CKD stages and duration of DOAC intake

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5. Fig. 4. Distribution of the administered drug among patients with GFR <45 ml/min/1.73m2

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6. Fig. 5. ROC curve method for predicting hemorrhagic events in patients taking dabigatran

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