rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2020-12-03rpcardio-2359Research ArticlePOINT OF VIEWТОЧКА ЗРЕНИЯThe Oral Anticoagulants Administration in Elderly Patients with Geriatric Syndromes: What's New?Применение пероральных антикоагулянтов у пожилых пациентов с гериатрическими синдромами: что нового?ВоробьеваН. М.VorobyevaN. M.

Воробьева Наталья Михайловна - доктор медицинских наук, заведующая лабораторией сердечно-сосудистого старения.129226, Москва, ул. 1-я Леонова, 16.

Natalya M. Vorobyeva - MD, PhD, Head of the Laboratory of Cardiovascular Aging, Pirogov Russian National Research Medical University, Russian Clinical and Research Center of Gerontology.Pervaya Leonova ul. 16, Moscow, 129226.

natalyavorobjeva@mail.ruТкачеваО. Н.TkachevaO. N.

Ткачева Ольга Николаевна – доктор медицинских наук, профессор, директор.129226, Москва, ул. 1-я Леонова, 16.

Olga N. Tkacheva - MD, PhD, Professor, Director, Pirogov Russian National Research Medical University, Russian Clinical and Research Center of Gerontology.Pervaya Leonova ul. 16, Moscow, 129226.

Российский национальный исследовательский медицинский университет им. Н.И. Пирогова -ОСП «Российский геронтологический научно-клинический центр»РоссияPirogov Russian National Research Medical University, Russian Clinical and Research Center of GerontologyRussian Federation202030122020166984993Copyright © Vorobyeva N.M., Tkacheva O.N., 20202020Воробьева Н.М., Ткачева О.Н.Vorobyeva N.M., Tkacheva O.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpcardio.online/jour/article/view/2359

The administration of oral anticoagulants in elderly patients with geriatric syndromes such as senile asthenia syndrome, falls and high risk of falls, dementia, polymorbidity, polypharmacy are discussed in the article. The evidence base for the anticoagulants taking in patients with atrial fibrillation aged ≥75, ≥80, ≥85 and ≥90 years, in patients with atrial fibrillation and various geriatric syndromes, as well as in elderly patients with venous thromboembolic complications and frailty syndrome is presented. Most studies indicate significant advantages of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) over the vitamin K antagonist warfarin in elderly patients with geriatric syndromes. An updated version of the FORTA consensus document, which aims to optimize the prescription of medicines for the elderly, is also presented. Apixaban has a FORTA-A safety class and is the safest oral anticoagulant in elderly patients.

В обзорной статье обсуждаются вопросы применения пероральных антикоагулянтов у пожилых пациентов с гериатрическими синдромами, такими как синдром старческой астении, падения и высокий риск падений, деменция, полиморбидность, полипрагмазия. Рассмотрена доказательная база по использованию антикоагулянтов у пациентов с фибрилляцией предсердий в возрасте ≥75, ≥80, ≥85 и ≥90 лет, у пациентов с фибрилляцией предсердий и различными гериатрическими синдромами, а также у пожилых пациентов с венозными тромбоэмболическими осложнениями и синдромом «хрупкости». Результаты подавляющего большинства исследований указывают на значительные преимущества прямых пероральных антикоагулянтов (дабигатрана, ривароксабана, апиксабана и эдоксабана) над антагонистом витамина К варфарином у пожилых пациентов с гериатрическими синдромами. Также представлена обновленная версия консенсусного документа FORTA, целью которого является оптимизация назначения лекарственных средств пожилым людям. По мнению экспертов FORTA, апиксабан имеет класс безопасности FORTA-A и является наиболее безопасным пероральным антикоагулянтом для пожилых пациентов.

пожилой пациентгериатрический синдромпероральные антикоагулянтыфибрилляция предсердийстарческая астениявенозные тромбоэмболические осложненияelderly patientgeriatric syndromeoral anticoagulantsatrial fibrillationsenile astheniavenous thromboembolic complicationsСтатья опубликована при финансовой поддержке компании Пфайзер.The article was published with the financial support of the Pfizer company.ReferencesBeard J.R., Officer A., de Carvalho I.A., et al. The World report on ageing and health: a policy framework for healthy ageing. Lancet. 2016;387(10033):2145-54. DOI:10.1016/S0140-6736(15)00516-4.Beard J.R., Officer A., de Carvalho I.A., et al. The World report on ageing and health: a policy framework for healthy ageing. Lancet. 2016;387(10033):2145-54. DOI:10.1016/S0140-6736(15)00516-4.Shah S.J., Fang M.C., Jeon S.Y., et al. Geriatric Syndromes and Atrial Fibrillation: Prevalence and Association with Anticoagulant Use in a National Cohort of Older Americans. J Am Geriatr Soc. 2020. DOI:10.1111/jgs.16822.Shah S.J., Fang M.C., Jeon S.Y., et al. Geriatric Syndromes and Atrial Fibrillation: Prevalence and Association with Anticoagulant Use in a National Cohort of Older Americans. J Am Geriatr Soc. 2020. DOI:10.1111/jgs.16822.Hindricks G., Potpara T., Dagres N., et al. ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2020;00:1-126. DOI:10.1093/eurheartj/ehaa612.Hindricks G., Potpara T., Dagres N., et al. ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2020;00:1-126. DOI:10.1093/eurheartj/ehaa612.Connolly S.J., Ezekowitz M.D., Yusuf S., et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-51. DOI:10.1056/NEJMoa0905561.Connolly S.J., Ezekowitz M.D., Yusuf S., et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-51. DOI:10.1056/NEJMoa0905561.Patel M.R., Mahaffey K.W., Garg J., et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883-91. DOI:10.1056/NEJMoa1009638.Patel M.R., Mahaffey K.W., Garg J., et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883-91. DOI:10.1056/NEJMoa1009638.Granger C.B., Alexander J.H., McMurray J.J., et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-92. DOI:10.1056/NEJMoa1107039.Granger C.B., Alexander J.H., McMurray J.J., et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-92. DOI:10.1056/NEJMoa1107039.Giugliano R.P., Ruff C.T., Braunwald E., et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093-104. DOI:10.1056/NEJMoa1310907.Giugliano R.P., Ruff C.T., Braunwald E., et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093-104. DOI:10.1056/NEJMoa1310907.Grymonprez M., Steurbaut S., De Backer T.L., et al. Effectiveness and Safety of Oral Anticoagulants in Older Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis. Front Pharmacol. 2020;11:583311. DOI:10.3389/fphar.2020.583311.Grymonprez M., Steurbaut S., De Backer T.L., et al. Effectiveness and Safety of Oral Anticoagulants in Older Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis. Front Pharmacol. 2020;11:583311. DOI:10.3389/fphar.2020.583311.Deitelzweig S., Keshishian A., Li X., et al. Comparisons between Oral Anticoagulants among Older Nonvalvular Atrial Fibrillation Patients. J Am Geriatrics Soc. 2019;67(8):1662-71. DOI:10.1111/jgs.15956.Deitelzweig S., Keshishian A., Li X., et al. Comparisons between Oral Anticoagulants among Older Nonvalvular Atrial Fibrillation Patients. J Am Geriatrics Soc. 2019;67(8):1662-71. DOI:10.1111/jgs.15956.Kim H.M., Choi E.K., Park C.S., et al. Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in octogenarian patients with non-valvular atrial fibrillation. PloS One. 2019;14(3):e0211766. DOI:10.1371/journal.pone.0211766.Kim H.M., Choi E.K., Park C.S., et al. Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in octogenarian patients with non-valvular atrial fibrillation. PloS One. 2019;14(3):e0211766. DOI:10.1371/journal.pone.0211766.Russo V., Attena E., Di Maio M., et al. Clinical profile of direct oral anticoagulants versus vitamin K anticoagulants in octogenarians with atrial fibrillation: a multicentre propensity score matched real-world cohort study. J Thromb Thrombolysis. 2019;49(1):42-53. DOI:10.1007/s11239-019-01923-9.Russo V., Attena E., Di Maio M., et al. Clinical profile of direct oral anticoagulants versus vitamin K anticoagulants in octogenarians with atrial fibrillation: a multicentre propensity score matched real-world cohort study. J Thromb Thrombolysis. 2019;49(1):42-53. DOI:10.1007/s11239-019-01923-9.Shinohara M., Wada R., Yao S., et al. Evaluation of oral anticoagulants in atrial fibrillation patients over 80 years of age with nonsevere frailty. J Arrhythmia. 2019;35(6):795-803. DOI:10.1002/joa3.12231.Shinohara M., Wada R., Yao S., et al. Evaluation of oral anticoagulants in atrial fibrillation patients over 80 years of age with nonsevere frailty. J Arrhythmia. 2019;35(6):795-803. DOI:10.1002/joa3.12231.Lai C.L., Chen H.M., Liao M.T., Lin T.T. Dabigatran, Rivaroxaban, and Warfarin in the Oldest Adults with Atrial Fibrillation in Taiwan. J Am Geriatrics Soc. 2018;66(8):1567-74. DOI:10.1111/jgs.15430.Lai C.L., Chen H.M., Liao M.T., Lin T.T. Dabigatran, Rivaroxaban, and Warfarin in the Oldest Adults with Atrial Fibrillation in Taiwan. J Am Geriatrics Soc. 2018;66(8):1567-74. DOI:10.1111/jgs.15430.Poli D., Antonucci E., Ageno W., et al. Oral anticoagulation in very elderly patients with atrial fibrillation: Results from the prospective multicenter START2-REGISTER study. PloS One. 2019;14(5):e0216831. DOI:10.1371/journal.pone.0216831.Poli D., Antonucci E., Ageno W., et al. Oral anticoagulation in very elderly patients with atrial fibrillation: Results from the prospective multicenter START2-REGISTER study. PloS One. 2019;14(5):e0216831. DOI:10.1371/journal.pone.0216831.Giustozzi M., Vedovati M.C., Verso M., et al. Patients aged 90years or older with atrial fibrillation treated with oral anticoagulants: A multicentre observational study. Int J Cardiol. 2019;281:56-61. DOI:10.1016/j.ijcard.2019.01.071.Giustozzi M., Vedovati M.C., Verso M., et al. Patients aged 90years or older with atrial fibrillation treated with oral anticoagulants: A multicentre observational study. Int J Cardiol. 2019;281:56-61. DOI:10.1016/j.ijcard.2019.01.071.Kwon S., Lee S.R., Choi E.K., et al. Non-vitamin K antagonist oral anticoagulants in very elderly east Asians with atrial fibrillation: A nationwide population-based study. Am Heart J. 2020;229:81-91. DOI:10.1016/j.ahj.2020.08.006.Kwon S., Lee S.R., Choi E.K., et al. Non-vitamin K antagonist oral anticoagulants in very elderly east Asians with atrial fibrillation: A nationwide population-based study. Am Heart J. 2020;229:81-91. DOI:10.1016/j.ahj.2020.08.006.Raposeiras-Roubin S., Alonso Rodriguez D., Camacho Freire S.J., et al. Vitamin K Antagonists and Direct Oral Anticoagulants in Nonagenarian Patients With Atrial Fibrillation. J Am Med Directors Assoc. 2020;21(3):367-373.e1. DOI:10.1016/j.jamda.2019.08.033.Raposeiras-Roubin S., Alonso Rodriguez D., Camacho Freire S.J., et al. Vitamin K Antagonists and Direct Oral Anticoagulants in Nonagenarian Patients With Atrial Fibrillation. J Am Med Directors Assoc. 2020;21(3):367-373.e1. DOI:10.1016/j.jamda.2019.08.033.Shah S.J., Singer D.E., Fang M.C., et al. Net Clinical Benefit of Oral Anticoagulation Among Older Adults With Atrial Fibrillation. Circ Cardiovasc Qual Outcomes. 2019;12(11):e006212. DOI:10.1161/CIRCOUTCOMES.119.006212.Shah S.J., Singer D.E., Fang M.C., et al. Net Clinical Benefit of Oral Anticoagulation Among Older Adults With Atrial Fibrillation. Circ Cardiovasc Qual Outcomes. 2019;12(11):e006212. DOI:10.1161/CIRCOUTCOMES.119.006212.Alexander K.P., Brouwer M.A., Mulder H., et al. Outcomes of apixaban versus warfarin in patients with atrial fibrillation and multi-morbidity: Insights from the ARISTOTLE trial. Am Heart J. 2019;208:123-31. DOI:10.1016/j.ahj.2018.09.017.Alexander K.P., Brouwer M.A., Mulder H., et al. Outcomes of apixaban versus warfarin in patients with atrial fibrillation and multi-morbidity: Insights from the ARISTOTLE trial. Am Heart J. 2019;208:123-31. DOI:10.1016/j.ahj.2018.09.017.Jaspers Focks J., Brouwer M.A., Wojdyla D.M., et al. Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial. BMJ. 2016;353:i2868. DOI:10.1136/bmj.i2868.Jaspers Focks J., Brouwer M.A., Wojdyla D.M., et al. Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial. BMJ. 2016;353:i2868. DOI:10.1136/bmj.i2868.Piccini J.P., Hellkamp A.S., Washam J.B., et al. Polypharmacy and the Efficacy and Safety of Rivaroxaban Versus Warfarin in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation. Circulation. 2016;133(4):352-60. DOI:10.1161/CIRCULATIONAHA.115.018544.Piccini J.P., Hellkamp A.S., Washam J.B., et al. Polypharmacy and the Efficacy and Safety of Rivaroxaban Versus Warfarin in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation. Circulation. 2016;133(4):352-60. DOI:10.1161/CIRCULATIONAHA.115.018544.Harskamp R.E., Teichert M., Lucassen W.A.M., et al. Impact of Polypharmacy and P-Glycoprotein-and CYP3A4-Modulating Drugs on Safety and Efficacy of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation. Cardiovasc Drugs Ther. 2019;33(5):615-23. DOI:10.1007/s10557-019-06907-8.Harskamp R.E., Teichert M., Lucassen W.A.M., et al. Impact of Polypharmacy and P-Glycoprotein-and CYP3A4-Modulating Drugs on Safety and Efficacy of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation. Cardiovasc Drugs Ther. 2019;33(5):615-23. DOI:10.1007/s10557-019-06907-8.Kim I.S., Kim H.J., Yu H.T., et al. Non-vitamin K antagonist oral anticoagulants with amiodarone, P-glycoprotein inhibitors, or polypharmacy in patients with atrial fibrillation: Systematic review and meta-analysis. J Cardiol. 2019;73(6):515-21. DOI:10.1016/j.jjcc.2018.12.018.Kim I.S., Kim H.J., Yu H.T., et al. Non-vitamin K antagonist oral anticoagulants with amiodarone, P-glycoprotein inhibitors, or polypharmacy in patients with atrial fibrillation: Systematic review and meta-analysis. J Cardiol. 2019;73(6):515-21. DOI:10.1016/j.jjcc.2018.12.018.Man-Son-Hing M., Nichol G., Lau A., et al. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med. 1999;159:677-85. DOI:10.1001/archinte.159.7.677.Man-Son-Hing M., Nichol G., Lau A., et al. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med. 1999;159:677-85. DOI:10.1001/archinte.159.7.677.Rao M.P., Vinereanu D., Wojdyla D.M., et al. Clinical Outcomes and History of Fall in Patients with Atrial Fibrillation Treated with Oral Anticoagulation: Insights From the ARISTOTLE Trial. Am J Med. 2018;131:269-75.e2. DOI:10.1016/j.amjmed.2017.10.036.Rao M.P., Vinereanu D., Wojdyla D.M., et al. Clinical Outcomes and History of Fall in Patients with Atrial Fibrillation Treated with Oral Anticoagulation: Insights From the ARISTOTLE Trial. Am J Med. 2018;131:269-75.e2. DOI:10.1016/j.amjmed.2017.10.036.Steffel J., Giugliano R.P., Braunwald E., et al. Edoxaban Versus Warfarin in Atrial Fibrillation Patients at Risk of Falling: ENGAGE AF-TIMI 48 Analysis. J Am CollCardiol. 2016;68(11):1169-78. DOI:10.1016/j.jacc.2016.06.034.Steffel J., Giugliano R.P., Braunwald E., et al. Edoxaban Versus Warfarin in Atrial Fibrillation Patients at Risk of Falling: ENGAGE AF-TIMI 48 Analysis. J Am CollCardiol. 2016;68(11):1169-78. DOI:10.1016/j.jacc.2016.06.034.Ткачева О.Н., Котовская Ю.В., Рунихина Н.К., и др. Старческая астения. Клинические рекомендации. Российский Журнал Гериатрической Медицины. 2020;1:11-46. DOI:10.37586/2686-8636-1-2020-11-46.Tkacheva O.N., Kotovskaya Y.V., Runikhina N.K., et al. Senile asthenia. Clinical guidelines. Russian Journal of Geriatric Medicine. 2020;1:11-46 (In Russ.) DOI:10.37586/2686-8636-1-2020-11-46.Kim S., Yoon S., Choi J., et al. Clinical implication of frailty assessment in older patients with atrial fibrillation. Arch GerontolGeriatr. 2017;70:1-7. DOI:10.1016/j.archger.2016.12.001.Kim S., Yoon S., Choi J., et al. Clinical implication of frailty assessment in older patients with atrial fibrillation. Arch GerontolGeriatr. 2017;70:1-7. DOI:10.1016/j.archger.2016.12.001.Perera V., Bajorek B.V., Matthews S., et al. The impact of frailty on the utilisation of antithrombotic therapy in older patients with atrial fibrillation. Age Ageing. 2009;38:156-62. DOI:10.1093/ageing/afn293.Perera V., Bajorek B.V., Matthews S., et al. The impact of frailty on the utilisation of antithrombotic therapy in older patients with atrial fibrillation. Age Ageing. 2009;38:156-62. DOI:10.1093/ageing/afn293.Nguyen T. N., Morel-Kopp M. C., Pepperell D. et al. The impact of frailty on coagulation and responses to warfarin in acute older hospitalised patients with atrial fibrillation: A pilot study. Aging Clin Exp Res. 2017;29:1129-38. DOI:10.1007/s40520-017-0733-8.Nguyen T. N., Morel-Kopp M. C., Pepperell D. et al. The impact of frailty on coagulation and responses to warfarin in acute older hospitalised patients with atrial fibrillation: A pilot study. Aging Clin Exp Res. 2017;29:1129-38. DOI:10.1007/s40520-017-0733-8.Lip G.Y.H., Banerjee A., Boriani G., et al. Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report. Chest. 2018;154:1121-201. DOI:10.1016/j.chest.2018.07.040.Lip G.Y.H., Banerjee A., Boriani G., et al. Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report. Chest. 2018;154:1121-201. DOI:10.1016/j.chest.2018.07.040.Induruwa I., Evans N.R., Aziz A., et al. Clinical frailty is independently associated with non-prescription of anticoagulants in older patients with atrial fibrillation. Geriatr Gerontol Int. 2017;17(11):2178-83. DOI:10.1111/ggi.13058.Induruwa I., Evans N.R., Aziz A., et al. Clinical frailty is independently associated with non-prescription of anticoagulants in older patients with atrial fibrillation. Geriatr Gerontol Int. 2017;17(11):2178-83. DOI:10.1111/ggi.13058.Ткачева О.Н., Котовская Ю.В., Рунихина Н.К., и др. Клинические рекомендации «Старческая астения». Часть 2. Российский Журнал Гериатрической Медицины. 2020;2:115-30. DOI:10.37586/2686-8636-2-2020-115-130.Tkacheva O.N., Kotovskaya Y.V., Runikhina N.K., et al. Clinical guidelines "Senile asthenia". Part 2. Russian Journal of Geriatric Medicine. 2020;2:115-30 (In Russ.) DOI:10.37586/2686-8636-2-2020-115-130.Martinez B.K., Sood N.A., Bunz T.J., Coleman C.I. Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin in Frail Patients With Nonvalvular Atrial Fibrillation. J Am Heart Assoc. 2018;7:e008643. DOI:10.1161/JAHA.118.008643.Martinez B.K., Sood N.A., Bunz T.J., Coleman C.I. Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin in Frail Patients With Nonvalvular Atrial Fibrillation. J Am Heart Assoc. 2018;7:e008643. DOI:10.1161/JAHA.118.008643.Lip G.Y.H., Keshishian A.V., Kang A.L., et al. Oral anticoagulants for nonvalvular atrial fibrillation in frail elderly patients: insights from the ARISTOPHANES study. J Intern Med. 2020. DOI:10.1111/joim.13140.Lip G.Y.H., Keshishian A.V., Kang A.L., et al. Oral anticoagulants for nonvalvular atrial fibrillation in frail elderly patients: insights from the ARISTOPHANES study. J Intern Med. 2020. DOI:10.1111/joim.13140.Prins M.H., Lensing A.W., Bauersachs R., et al., EINSTEIN Investigators: Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J. 2013;11:21. DOI:10.1186/1477-9560-11-21.Prins M.H., Lensing A.W., Bauersachs R., et al., EINSTEIN Investigators: Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J. 2013;11:21. DOI:10.1186/1477-9560-11-21.Buller H.R., Decousus H., Grosso M.A., et al.; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369(15):1406-15. DOI:10.1056/NEJMoa1306638.Buller H.R., Decousus H., Grosso M.A., et al.; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369(15):1406-15. DOI:10.1056/NEJMoa1306638.Trujillo-Santos J., Beroiz P., Moustafa F., et al.; RIETE Investigators. Rivaroxaban or apixaban in fragile patients with acute venous thromboembolism. Thromb Res. 2020;193:160-5. DOI:10. 1016/j.thromres.2020.06.035.Trujillo-Santos J., Beroiz P., Moustafa F., et al.; RIETE Investigators. Rivaroxaban or apixaban in fragile patients with acute venous thromboembolism. Thromb Res. 2020;193:160-5. DOI:10. 1016/j.thromres.2020.06.035.Orkaby A.R., Ozonoff A., Reisman J.I., et al. Continued Use of Warfarin in Veterans with Atrial Fibrillation After Dementia Diagnosis. J Am Geriatrics Soc. 2017;65(2):249-56. DOI:10.1111/jgs.14573.Orkaby A.R., Ozonoff A., Reisman J.I., et al. Continued Use of Warfarin in Veterans with Atrial Fibrillation After Dementia Diagnosis. J Am Geriatrics Soc. 2017;65(2):249-56. DOI:10.1111/jgs.14573.Subic A., Cermakova P., Religa D., et al. Treatment of Atrial Fibrillation in Patients with Dementia: A Cohort Study from the Swedish Dementia Registry. J Alzheimers Dis. 2018;61(3):1119-28. DOI:10.3233/JAD-170575.Subic A., Cermakova P., Religa D., et al. Treatment of Atrial Fibrillation in Patients with Dementia: A Cohort Study from the Swedish Dementia Registry. J Alzheimers Dis. 2018;61(3):1119-28. DOI:10.3233/JAD-170575.Fanning L., Lau W.C.Y., Mongkhon P., et al. Safety and Effectiveness of Direct Oral Anticoagulants vs Warfarin in People With Atrial Fibrillation and Dementia. J Am Med Directors Assoc. 2020;21(8):1058-64.e6. DOI:10.1016/j.jamda.2019.11.022.Fanning L., Lau W.C.Y., Mongkhon P., et al. Safety and Effectiveness of Direct Oral Anticoagulants vs Warfarin in People With Atrial Fibrillation and Dementia. J Am Med Directors Assoc. 2020;21(8):1058-64.e6. DOI:10.1016/j.jamda.2019.11.022.Wehling M. Drug therapy in the elderly: too much or too little, what to do? A new assessment system: fit for the aged (FORTA) [in German]. Dtsch Med Wochenschr. 2008;133:2289-91. DOI:10.1055/s-0028-1091275.Wehling M. Drug therapy in the elderly: too much or too little, what to do? A new assessment system: fit for the aged (FORTA) [in German]. Dtsch Med Wochenschr. 2008;133:2289-91. DOI:10.1055/s-0028-1091275.Wehling M. Multimorbidity and polypharmacy: how to reduce the harmful drug load and yet add needed drugs in the elderly? Proposal of a new drug classification: fit for the aged. J Am Geriatr Soc. 2009;57:560-61. DOI:10.1111/j.1532-5415.2009.02131.x.Wehling M. Multimorbidity and polypharmacy: how to reduce the harmful drug load and yet add needed drugs in the elderly? Proposal of a new drug classification: fit for the aged. J Am Geriatr Soc. 2009;57:560-61. DOI:10.1111/j.1532-5415.2009.02131.x.Kuhn-Thiel A.M., Weiss C., Wehling M. Consensus validation of the FORTA (Fit fOR The Aged) List: a clinical tool for increasing the appropriateness of pharmacotherapy in the elderly. Drugs Aging. 2014;31:131-40. DOI:10.1007/s40266-013-0146-0.Kuhn-Thiel A.M., Weiss C., Wehling M. Consensus validation of the FORTA (Fit fOR The Aged) List: a clinical tool for increasing the appropriateness of pharmacotherapy in the elderly. Drugs Aging. 2014;31:131-40. DOI:10.1007/s40266-013-0146-0.Pazan F., Weiss C., Wehling M. The FORTA (Fit fOR The Aged) list 2018: third version of a validated clinical tool for improved drug treatment in older people. Drugs Aging. 2019;36:481-4. DOI:10.1007/s40266-019-00669-6.Pazan F., Weiss C., Wehling M. The FORTA (Fit fOR The Aged) list 2018: third version of a validated clinical tool for improved drug treatment in older people. Drugs Aging. 2019;36:481-4. DOI:10.1007/s40266-019-00669-6.Michalek C., Wehling M., Schlitzer J., Frohnhofen H. Effects of «Fit fOR The Aged» (FORTA) on pharmacotherapy and clinical endpoints — a pilot randomized controlled study. Eur J Clin Pharmacol. 2014;70:1261-7. DOI:10.1007/s00228-014-1731-9.Michalek C., Wehling M., Schlitzer J., Frohnhofen H. Effects of «Fit fOR The Aged» (FORTA) on pharmacotherapy and clinical endpoints — a pilot randomized controlled study. Eur J Clin Pharmacol. 2014;70:1261-7. DOI:10.1007/s00228-014-1731-9.Wehling M., Burkhardt H., Kuhn-Thiel A.M., et al. VALFORTA - a randomized trial to validate the FORTA («Fit fOR The Aged») classification. Age Ageing. 2016;45:262-7. DOI:10.1093/ageing/afv200.Wehling M., Burkhardt H., Kuhn-Thiel A.M., et al. VALFORTA - a randomized trial to validate the FORTA («Fit fOR The Aged») classification. Age Ageing. 2016;45:262-7. DOI:10.1093/ageing/afv200.Pazan F., Burkhardt H., Frohnhofen H., et al. Changes in prescription patterns in older hospitalized patients: the impact of FORTA on disease-related over- and under-treatments. Eur J Clin Pharmacol. 2018;74:339-47. DOI:10.1007/s00228-017-2383-3.Pazan F., Burkhardt H., Frohnhofen H., et al. Changes in prescription patterns in older hospitalized patients: the impact of FORTA on disease-related over- and under-treatments. Eur J Clin Pharmacol. 2018;74:339-47. DOI:10.1007/s00228-017-2383-3.Wehling M., Collins R., Gil V.M., et al. Appropriateness of oral anticoagulants for the long-term treatment of atrial fibrillation in older people. Results of an Evidence-Based Review and International Consensus Validation Process (OAC-FORTA 2016). Drugs Aging. 2017;34(7):499-507. DOI:10.1007/s40266-017-0466-6.Wehling M., Collins R., Gil V.M., et al. Appropriateness of oral anticoagulants for the long-term treatment of atrial fibrillation in older people. Results of an Evidence-Based Review and International Consensus Validation Process (OAC-FORTA 2016). Drugs Aging. 2017;34(7):499-507. DOI:10.1007/s40266-017-0466-6.Воробьева Н.М., Ткачева О.Н. Антикоагулянтная терапия у пожилых пациентов: дилемма выбора между эффективностью и безопасностью. Медицинский Алфавит. 2018;2(16):6-14.Vorob'eva N.M., Tkacheva O.N. Anticoagulant therapy in elderly patients: the dilemma of choosing between efficacy and safety. Medical Alphabet. 2018;2(16):6-14 (In Russ.).Воробьева Н. М., Ткачева О. Н. Пожилой пациент с фибрилляцией предсердий: как повысить безопасность антикоагулянтной терапии? Доктор.Ру. 2019;10(165):16-22. DOI:10.31550/1727-2378-2019-165-10-16-22.Vorobyova N.M., Tkacheva O. N. Elderly patient with atrial fibrillation: how to increase the safety of anticoagulant therapy? Doctor.Ru. 2019;10(165):16-22 (In Russ.). DOI:10.31550/1727-2378-2019-165-10-16-22.Pazan F., Collins R., Gil V.M., et al. A Structured Literature Review and International Consensus Validation of FORTA Labels of Oral Anticoagulants for Long-Term Treatment of Atrial Fibrillation in Older Patients (OAC-FORTA 2019). Drugs Aging. 2020;37:539-48. DOI:10.1007/s40266-020-00771-0.Pazan F., Collins R., Gil V.M., et al. A Structured Literature Review and International Consensus Validation of FORTA Labels of Oral Anticoagulants for Long-Term Treatment of Atrial Fibrillation in Older Patients (OAC-FORTA 2019). Drugs Aging. 2020;37:539-48. DOI:10.1007/s40266-020-00771-0.

The authors declare that there are no conflicts of interest present.