Polypragmasy in elderly and senile patients with chronic kidney disease: START/STOP criteria in elderly and senile patients taking DOAC

封面
  • 作者: Kondrakhin A.P.1,2, Silina E.G.3, Chernyaeva M.S.2,4, Maksimov M.L.1,5,6, Babichev A.N.1, Smirnova Y.E.1, Martynova S.A.1, Schnаider K.O.1,6
  • 隶属关系:
    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. Kazan State Medical Academy – branch of the Russian Medical Academy of Continuous Professional Education of the Ministry of Health of Russia
    6. Federal State Budgetary Educational Institution of Additional Professional Education “Russian Medical Academy of Continuous Professional Education”, Ministry of Health of Russia
  • 期: 卷 23, 编号 5 (2025)
  • 页面: 49-60
  • 栏目: Original research
  • URL: https://journals.eco-vector.com/1728-2918/article/view/696271
  • DOI: https://doi.org/10.29296/24999490-2025-05-07
  • ID: 696271

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详细

Introduction. Thanks to the achievements of modern medicine, it was possible to significantly increase the life expectancy of the population. Molecular mechanisms of aging include telomere shortening, DNA damage accumulation, mitochondrial dysfunction, leading to decreased functional reserves of organs and systems. The cohort of geriatric patients is at risk of polypragmasy and has features of drug pharmacokinetics.

Objective: To evaluate factors that increase the risk of taking direct oral anticoagulants in elderly patients with polypragmasy and chronic kidney disease taking into account molecular mechanisms of drug action and individual pharmacogenetic features.

Material and methods. For this study, a database of 503 patients seen in «GVH No.2 DZM» from April to September 2023 was collected. The method of questionnaire was used, as well as the collection of clinical and laboratory data allowing to evaluate DOAC-dependent complications – cases of bleeding, duration of DOAC administration. Additionally, renal function biomarkers (cystatin C, NGAL), coagulation parameters and CYP3A4/CYP2C19 activity by indirect markers were analyzed.

Results. DOAC administration increases bleeding risks when creatinine clearance is significantly decreased, especially when dabigatran is administered. Administration of apixaban and rivaroxaban have no statistically significant increase in the incidence of hemorrhagic complications as renal impairment progresses. Concomitant DOAC and heparins significantly increase the risk of bleeding during 1 year of therapy. Co-administration of dabigatran and verapamil increases the risk of bleeding, which is not seen with other DOACs.

Conclusion. Investigation of drug interactions and the association of DOAC intake with various endpoints in larger samples will help to identify predictors of adverse outcomes and adjust therapy. Personalized approach considering pharmacogenetic features and molecular biomarkers can significantly improve the safety of anticoagulant therapy in elderly patients.

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作者简介

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”

编辑信件的主要联系方式.
Email: 79104851199@yandex.ru
ORCID iD: 0000-0002-3439-8059
SPIN 代码: 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

俄罗斯联邦, 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: kafedrakf@mail.ru
ORCID iD: 0000-0003-0406-3888
SPIN 代码: 2245-4442

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

俄罗斯联邦, 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 代码: 2244-0320

Candidate of Medical Sciences, Head of the Geriatric Department, Associate Professor, Department of Internal Diseases and Preventive Medicine

俄罗斯联邦, 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; Kazan State Medical Academy – branch of the Russian Medical Academy of Continuous Professional Education of the Ministry of Health of Russia; 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 代码: 6261-3982

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

俄罗斯联邦, Ostrovityanova str., 1, Moscow, 117997; Butlerova st., 49, Kazan, Republic of Tatarstan, 420012; Barrikadnaya st., 2/1, Moscow, 123995

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

4rd year student of the Institute of Clinical Medicine

俄罗斯联邦, 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

4rd year student at the Institute of Motherhood and Childhood

俄罗斯联邦, 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

5rd year student at the Institute of Motherhood and Childhood

俄罗斯联邦, Ostrovityanova str., 1, Moscow, 117997

Ksenia Schnаider

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 代码: 9979-2700

assistant at the Department of Pharmacology at the Institute of Pharmacy and Medical Chemistry, and an assistant at the Department of Pharmacy, General Pharmacology, and Pharmaceutical Counseling

俄罗斯联邦, Ostrovityanova str., 1, Moscow, 117997; Barrikadnaya st., 2/1, Moscow, 123995

参考

  1. López-Otero D., Trillo-Nouche R., González-Ferreiro R., et al. Molecular mechanisms of aging and anticoagulation: implications for personalized medicine. Nature Aging. 2019; 1: 234–45. DOI: https://doi.org/10,1038/s41586-019-1365-2
  2. Heijman J., Voigt N., Nattel S., Dobrev D. Cellular and molecular electrophysiology of atrial fibrillation initiation, maintenance, and progression. Circ Res. 2014; 114 (9): 1483–99. DOI: https://doi.org/10,1161/CIRCRESAHA.114.302226
  3. Maher R.L., Hanlon J., Hajjar E.R. Clinical consequences of polypharmacy in elderly. Expert Opin Drug Saf. 2014; 13 (1): 57–65. DOI: https://doi.org/10,1517/14740338.2013.827660.
  4. Tornio A., Backman J.T. Cytochrome P450 in pharmacogenetics: an update. Adv Pharmacol. 2018; 83: 3–32. DOI: https://doi.org/10,1016/bs.apha.2018.04.007
  5. Steffel J., Verhamme P., Potpara T.S. et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur. Heart J. 2018; 39 (16): 1330–93. DOI: https://doi.org/10,1093/eurheartj/ehy136
  6. Ruff C.T., Giugliano R.P., Braunwald E. et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014; 383 (9921): 955–62. DOI: https://doi.org/10,1016/S0140-6736(13)62343-0
  7. 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.
  8. Asiimwe I.G., Zhang E.J., Osanlou R. et al. Warfarin dosing algorithms: a systematic review. Br. J. Clin. Pharmacol. 2020; 87 (4): 1717–29. DOI: https://doi.org/10,1111/bcp.14608
  9. Machado-Duque M.E., Castaño-Montoya J.P., Medina-Morales D.A., Castro-Rodriguez A., González-Montoya A., Machado-Alba J.E. 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: 10,1177/0891988718757370, Epub 2018 Mar 11. PMID: 29528764.
  10. Ostermann M., Bellomo R., Burdmann E.A., et al. Controversies in acute kidney injury: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference. Kidney Int. 2020; 98 (2): 294–309. DOI: https://doi.org/10,1016/j.kint.2020,04.020
  11. Weitz J.I., Fredenburgh J.C., Eikelboom J.W. A Test in Context: D-Dimer. J Am Coll Cardiol. 2017; 70 (19): 2411–20. DOI: https://doi.org/10,1016/j.jacc.2017.09.024
  12. Härtter S., Sennewald R., Nehmiz G., Reilly P. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects. Br. J. Clin. Pharmacol. 2013; 75 (4): 1053–62. DOI: https://doi.org/10,1111/j.1365-2125.2012.04453.x
  13. Heidbuchel H., Verhamme P., Alings M. et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2015; 17 (10): 1467–507. DOI: https://doi.org/10,1093/europace/euv309
  14. 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.
  15. Leelakanok N., Holcombe A.L, Lund B.C., et al. Association between polypharmacy and death: A systematic review and metaanalysis. J. Am. Pharm Assoc. 2017; 57 (6): 729–38. DOI: https://doi.org/10,1016/j.japh.2017.06.002
  16. Johnson J.A., Caudle K.E., Gong L. et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update. Clin Pharmacol Ther. 2017; 102 (3): 397–404. DOI: https://doi.org/10,1002/cpt.668
  17. Baruth J.M., Gentry M.T, Rummans T.A. et al. Multidisciplinary Guideline for Polypharmacy in older people. Hosp Pract (1995). 2020; 48 (1): 56–62. DOI: https://doi.org/10,1080/21548331.2019.1706995
  18. Tripodi A. Thrombin Generation Assay and Its Application in the Clinical Laboratory. Clin Chem. 2016; 62 (5): 699–707. DOI: https://doi.org/10,1373/clinchem.2015.248625
  19. Steffel J., Collins R., Antz M. et al. 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation. Europace. 2021; 23 (10): 1612–76. DOI: https://doi.org/10,1093/europace/euab065
  20. Shameer K., Johnson K.W., Glicksberg B.S. et al. Machine learning in cardiovascular medicine: are we there yet? Heart. 2018; 104 (14): 1156–64. DOI: https://doi.org/10,1136/heartjnl-2017-311198

补充文件

附件文件
动作
1. JATS XML
2. Fig. 1. Number of drugs taken

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3. Fig. 2. Popularity of prescribing various drug groups together with DOAC

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4. Fig. 3. Distribution of patients by CKD stages

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

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