cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLC10.15829/1728-8800-2021-3044cardiovascular-3044Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEW ARTICLESПроблемы выбора антикоагулянта для вторичной профилактики инсульта у пациентов с фибрилляцией предсердийProblems of selecting an anticoagulant for secondary stroke prevention in patients with atrial fibrillationhttps://orcid.org/0000-0003-2232-7074ГусевВ. В.GusevV. V.

Кандидат медицинских наук, зав. неврологическим отделением, научный сотрудник лаборатории нейротехнологии, доцент кафедры нервных болезней, нейрохирургии и медицинской генетики.

 

Екатеринбург, SPIN: 9469-8054 

Yekaterinburg

gusev_vadim@inbox.ruhttps://orcid.org/0000-0002-2280-3096ЛьвоваО. А.LvovaO. A.

Доктор медицинских наук, доцент, ведущий инженер лаборатории нейротехнологии, старший научный сотрудник лаборатории внутриутробного программирования ЦНИЛ.

 

Екатеринбург, Тел.: +7 (922) 209-32-59, SPIN: 1761-5954, 

Yekaterinburg

olvova@bk.ruhttps://orcid.org/0000-0001-6250-0762ШамаловН. А.ShamalovN. A.

Доктор медицинских наук, доцент, ведущий инженер лаборатории нейротехнологии, старший научный сотрудник лаборатории внутриутробного программирования ЦНИЛ.

Екатеринбург, Тел.: +7 (922) 209-32-59

Moscow

shamalov@gmail.comГАУЗ СО Центральная городская клиническая больница № 23; ФГАОУ ВО Уральский федеральный университет имени первого Президента России Б.Н. Ельцина; ФГБОУ ВО Уральский государственный медицинский университет Минздрава РоссииCentral City Clinical Hospital № 23; Ural Federal University named after the First President of Russia B.N. Yeltsin; Ural State Medical UniversityФГАОУ ВО Уральский федеральный университет имени первого Президента России Б.Н. Ельцина; ФГБОУ ВО Уральский государственный медицинский университет Минздрава РоссииUral Federal University named after the First President of Russia B.N. Yeltsin; Ural State Medical UniversityИнститут цереброваскулярной патологии и инсульта, ФГБУ Федеральный центр мозга и нейротехнологий ФМБА РоссииInstitute of Cerebrovascular Pathology and Stroke, Federal Center of Brain Research and Neurotechnologies20211510202120630443044Copyright © Гусев В.В., Львова О.А., Шамалов Н.А., 20212021Гусев В.В., Львова О.А., Шамалов Н.А.Gusev V.V., Lvova O.A., Shamalov N.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/3044

Статья посвящена актуальной проблеме профилактики ишемического инсульта у пациентов с фибрилляцией предсердий (ФП). Доказано, что ишемический инсульт на фоне этой патологии является наиболее тяжелым в плане развития стойких двигательных и речевых нарушений, потери независимости. Особую проблему с этой точки зрения представляют, так называемые, пожилые “хрупкие” пациенты, а также пациенты с нарушением глотания и сниженной комплаентностью. Наиболее известные клинические исследования, посвященные проблеме вторичной профилактики кардиоэмболического инсульта — RE-LY, ROCKET-AF, ARISTOTLE. По результатам субанализов в этих рандомизированных контролируемых исследованиях прямые пероральные антикоагулянты продемонстрировали благоприятный профиль эффективности у пациентов с ФП и перенесенным инсультом/транзиторной ишемической атакой в анамнезе, однако степень изученности каждого из них оставалась разной. Продемонстрирован ряд преимуществ препарата ривароксабан в системе первичной и вторичной профилактики инсульта у пациентов с ФП, включая пожилых и пациентов с когнитивными нарушениями и нарушениями глотания.

The article describes the urgent problem of ischemic stroke prevention in patients with atrial fibrillation. It is proved that ischemic stroke in combination with AF is the most severe in terms of developing stable motor and speech disorders and disability. The frail older patients, as well as patients with swallowing disorders and reduced medical adherence present a special problem from this point of view. The most famous clinical studies on secondary prevention of cardioembolic stroke are RE-LY, ROCKET-AF, and ARISTOTLE. Based on subanalyses of randomized controlled trials, direct oral anticoagulants demonstrated a favorable efficacy profile in patients with atrial fibrillation and stroke/ transient ischemic attack, but the level of knowledge on each of them remained different. A number of advantages of rivaroxaban for primary and secondary prevention of stroke in patients with atrial fibrillation, including the elderly and patients with cognitive impairments and swallowing disorders, have been demonstrated.

ишемический инсультфибрилляция предсердийвторичная профилактикапрямые пероральные антикоагулянтыischemic strokeatrial fibrillationsecondary preventiondirect oral anticoagulantsПубликация подготовлена при поддержке АО “Байер” (PP-M_RIV-RU-0058-1)This publication was supported by AO Bayer (PP-M_RIV-RU-0058-1)ReferencesHindricks 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 for 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. 2021;42(5):373-498. doi:10.1093/eurheartj/ehaa612. Erratum in: Eur Heart J. 2021;42(5):507. Erratum in: Eur Heart J. 2021;42(5):546-7.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 for 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. 2021;42(5):373-498. doi:10.1093/eurheartj/ehaa612. Erratum in: Eur Heart J. 2021;42(5):507. Erratum in: Eur Heart J. 2021;42(5):546-7.Adams HP Jr, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35-41. doi:10.1161/01.str.24.1.35.Adams HP Jr, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35-41. doi:10.1161/01.str.24.1.35.Lamassa M, Di Carlo A, Pracucci G, et al. Characteristics, outcome, and care of stroke associated with atrial fibrillation in Europe: data from a multicenter multinational hospital-based registry (The European Community Stroke Project). Stroke. 2001;32(2):392-8. doi:10.1161/01.str.32.2.392.Lamassa M, Di Carlo A, Pracucci G, et al. Characteristics, outcome, and care of stroke associated with atrial fibrillation in Europe: data from a multicenter multinational hospital-based registry (The European Community Stroke Project). Stroke. 2001;32(2):392-8. doi:10.1161/01.str.32.2.392.Saxena R, Lewis S, Berge E, et al. Risk of early death and recurrent stroke and effect of heparin in 3169 patients with acute ischemic stroke and atrial fibrillation in the International Stroke Trial. Stroke. 2001;32(10):2333-7. doi:10.1161/hs1001.097093.Saxena R, Lewis S, Berge E, et al. Risk of early death and recurrent stroke and effect of heparin in 3169 patients with acute ischemic stroke and atrial fibrillation in the International Stroke Trial. Stroke. 2001;32(10):2333-7. doi:10.1161/hs1001.097093.Hart RG, Coull BM, Hart D. Early recurrent embolism associated with nonvalvular atrial fibrillation: a retrospective study. Stroke. 1983;14(5):688-93.Hart RG, Coull BM, Hart D. Early recurrent embolism associated with nonvalvular atrial fibrillation: a retrospective study. Stroke. 1983;14(5):688-93.Berge E, Abdelnoor M, Nakstad PH, Sandset PM. Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: a double-blind randomised study. HAEST Study Group. Heparin in Acute Embolic Stroke Trial. Lancet. 2000;355(9211):1205-10. doi:10.1016/s0140-6736(00)02085-7.Berge E, Abdelnoor M, Nakstad PH, Sandset PM. Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: a double-blind randomised study. HAEST Study Group. Heparin in Acute Embolic Stroke Trial. Lancet. 2000;355(9211):1205-10. doi:10.1016/s0140-6736(00)02085-7.Paciaroni M, Agnelli G, Micheli S, Caso V. Efficacy and safety of anticoagulant treatment in acute cardioembolic stroke: a meta-analysis of randomized controlled trials. Stroke. 2007;38(2):423-30. doi:10.1161/01.STR.0000254600.92975.1f.Paciaroni M, Agnelli G, Micheli S, Caso V. Efficacy and safety of anticoagulant treatment in acute cardioembolic stroke: a meta-analysis of randomized controlled trials. Stroke. 2007;38(2):423-30. doi:10.1161/01.STR.0000254600.92975.1f.von Kummer R, Broderick JP, Campbell BC, et al. The Heidelberg Bleeding Classification: Classification of Bleeding Events After Ischemic Stroke and Reperfusion Therapy. Stroke. 2015;46(10):2981-6. doi:10.1161/STROKEAHA.115.010049.von Kummer R, Broderick JP, Campbell BC, et al. The Heidelberg Bleeding Classification: Classification of Bleeding Events After Ischemic Stroke and Reperfusion Therapy. Stroke. 2015;46(10):2981-6. doi:10.1161/STROKEAHA.115.010049.Paciaroni M, Agnelli G, Corea F, et al. Early hemorrhagic transformation of brain infarction: rate, predictive factors, and influence on clinical outcome: results of a prospective multicenter study. Stroke. 2008;39(8):2249-56. doi:10.1161/STROKEAHA.107.510321.Paciaroni M, Agnelli G, Corea F, et al. Early hemorrhagic transformation of brain infarction: rate, predictive factors, and influence on clinical outcome: results of a prospective multicenter study. Stroke. 2008;39(8):2249-56. doi:10.1161/STROKEAHA.107.510321.Kablau M, Kreisel SH, Sauer T, et al. Predictors and early outcome of hemorrhagic transformation after acute ischemic stroke. Cerebrovasc Dis. 2011;32(4):334-41. doi:10.1159/000331702.Kablau M, Kreisel SH, Sauer T, et al. Predictors and early outcome of hemorrhagic transformation after acute ischemic stroke. Cerebrovasc Dis. 2011;32(4):334-41. doi:10.1159/000331702.January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation. 2019;140(2):e125-e151. doi:10.1161/CIR.0000000000000665. Erratum in: Circulation. 2019;140(6):e285.January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation. 2019;140(2):e125-e151. doi:10.1161/CIR.0000000000000665. Erratum in: Circulation. 2019;140(6):e285.Аракелян М . Г ., Бокерия Л .А ., Васильева Е .Ю . и др. Фибрилляция и тре-петание предсердий. Клинические рекомендации 2020. Российский кардиологический журнал. 2021;26(7):4594. doi:10.15829/1560-4071-2021-4594.Arakelyan MG, Bockeria LA, Vasilieva EYu, et al. 2020 Clinical guidelines for Atrial fibrillation and atrial flutter. Russian Journal of Cardiology. 2021;26(7):4594. (In Russ.) doi:10.15829/1560-4071-2021-4594.Diener HC, Connolly SJ, Ezekowitz MD, et al; RE-LY study group. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol. 2010;9(12):1157-63. doi:10.1016/S1474-4422(10)70274-X. Erratum in: Lancet Neurol. 2011;10(1):27.Diener HC, Connolly SJ, Ezekowitz MD, et al; RE-LY study group. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol. 2010;9(12):1157-63. doi:10.1016/S1474-4422(10)70274-X. Erratum in: Lancet Neurol. 2011;10(1):27.Easton JD, Lopes RD, Bahit MC, et al; ARISTOTLE Committees and Investigators. Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial. Lancet Neurol. 2012;11(6):503-11. doi:10.1016/S1474-4422(12)70092-3. Err atum in: Lancet Neurol. 2012;11(12):1021.Easton JD, Lopes RD, Bahit MC, et al; ARISTOTLE Committees and Investigators. Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial. Lancet Neurol. 2012;11(6):503-11. doi:10.1016/S1474-4422(12)70092-3. Err atum in: Lancet Neurol. 2012;11(12):1021.Hankey GJ, Patel MR, Stevens SR, et al; ROCKET AF Steering Committee Investigators. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF. Lancet Neurol. 2012;11(4):315-22. doi:10.1016/S1474-4422(12)70042-X.Hankey GJ, Patel MR, Stevens SR, et al; ROCKET AF Steering Committee Investigators. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF. Lancet Neurol. 2012;11(4):315-22. doi:10.1016/S1474-4422(12)70042-X.Halvorsen S, Atar D, Yang H, et al. Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial. Eur Heart J. 2014;35(28):1864-72. doi:10.1093/eurheartj/ehu046.Halvorsen S, Atar D, Yang H, et al. Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial. Eur Heart J. 2014;35(28):1864-72. doi:10.1093/eurheartj/ehu046.Eikelboom JW, Wallentin L, Connolly SJ, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011;123(21):2363-72. doi:10.1161/CIRCULATIONAHA.110.004747.Eikelboom JW, Wallentin L, Connolly SJ, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011;123(21):2363-72. doi:10.1161/CIRCULATIONAHA.110.004747.Halperin JL, Hankey GJ, Wojdyla DM, et al. ROCKET AF Steering Committee and Investigators. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Circulation. 2014;130(2):138-46. doi:10.1161/CIRCULATIONAHA.113.005008.Halperin JL, Hankey GJ, Wojdyla DM, et al. ROCKET AF Steering Committee and Investigators. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Circulation. 2014;130(2):138-46. doi:10.1161/CIRCULATIONAHA.113.005008.Hanon O, Vidal JS, Pisica-Donose G, et al. SAFIR study group. Bleeding risk with rivaroxaban compared with vitamin K antagonists in patients aged 80 years or older with atrial fibrillation. Heart. 2021;107(17):1376-82. doi:10.1136/heartjnl-2020-317923.Hanon O, Vidal JS, Pisica-Donose G, et al. SAFIR study group. Bleeding risk with rivaroxaban compared with vitamin K antagonists in patients aged 80 years or older with atrial fibrillation. Heart. 2021;107(17):1376-82. doi:10.1136/heartjnl-2020-317923.Alberts M, Chen YW, Lin JH, et al. Risks of Stroke and Mortality in Atrial Fibrillation Patients Treated With Rivaroxaban and Warfarin. Stroke. 2020;51(2):549-55. doi:10.1161/STROKEAHA.119.025554.Alberts M, Chen YW, Lin JH, et al. Risks of Stroke and Mortality in Atrial Fibrillation Patients Treated With Rivaroxaban and Warfarin. Stroke. 2020;51(2):549-55. doi:10.1161/STROKEAHA.119.025554.Фонякин А. В. от имени рабочей группы исследователей. Применение риварок сабана для вторичной профилактики инсульта в реальной клинической практике. Результаты российского проспективного многоцентрового наблюдательного исследования Neuro-Xar. Кардиология. 2016;56(4):49-53. doi:10.18565/cardio.2016.4.49-53.Fonyakin AV. on behalf of the working group of researchers. Application Rivaroxaban for Secondary Stroke Prevention in Clinical Practice. Results of Russian Prospective, Multicenter, Observational Study NEURO-XAR. Kardiologiia. 2016;56(4):49-53. (In Russ.) doi:10.18565/cardio.2016.4.49-53.Coleman CI, Peacock WF, Bunz TJ, Alberts MJ. Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin in Patients with Nonvalvular Atrial Fibrillation and Previous Stroke or Transient Ischemic Attack. Stroke. 2017;48(8):2142-9. doi:10.1161/STROKEAHA.117.017474.Coleman CI, Peacock WF, Bunz TJ, Alberts MJ. Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin in Patients with Nonvalvular Atrial Fibrillation and Previous Stroke or Transient Ischemic Attack. Stroke. 2017;48(8):2142-9. doi:10.1161/STROKEAHA.117.017474.Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology. 2007;69(6):546-54. doi:10.1212/01.wnl.0000267275.68538.8d.Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology. 2007;69(6):546-54. doi:10.1212/01.wnl.0000267275.68538.8d.Marini C, De Santis F, Sacco S, et al. Contribution of atrial fibrillation to incidence and outcome of ischemic stroke: results from a population-based study. Stroke. 2005;36(6):1115-9. doi:10.1161/01.STR.0000166053.83476.4a.Marini C, De Santis F, Sacco S, et al. Contribution of atrial fibrillation to incidence and outcome of ischemic stroke: results from a population-based study. Stroke. 2005;36(6):1115-9. doi:10.1161/01.STR.0000166053.83476.4a.Lip GY, Frison L, Halperin JL, Lane DA. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. J Am Coll Cardiol. 2011;57(2):173-80. doi:10.1016/j.jacc.2010.09.024.Lip GY, Frison L, Halperin JL, Lane DA. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. J Am Coll Cardiol. 2011;57(2):173-80. doi:10.1016/j.jacc.2010.09.024.Paciaroni M, Agnelli G, Falocci N, et al. Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study. Stroke. 2015;46(8):2175-82. doi:10.1161/STROKEAHA.115.008891.Paciaroni M, Agnelli G, Falocci N, et al. Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study. Stroke. 2015;46(8):2175-82. doi:10.1161/STROKEAHA.115.008891.Gioia LC, Kate M, Sivakumar L, et al. Early Rivaroxaban Use After Cardioembolic Stroke May Not Result in Hemorrhagic Transformation: A Prospective Magnetic Resonance Imaging Study. Stroke. 2016;47(7):1917-9. doi:10.1161/STROKEAHA.116.013491.Gioia LC, Kate M, Sivakumar L, et al. Early Rivaroxaban Use After Cardioembolic Stroke May Not Result in Hemorrhagic Transformation: A Prospective Magnetic Resonance Imaging Study. Stroke. 2016;47(7):1917-9. doi:10.1161/STROKEAHA.116.013491.Miao B, Hernandez AV, Roman YM, et al. Four-year incidence of major adverse cardiovascular events in patients with atherosclerosis and atrial fibrillation. Clin Cardiol. 2020;43(5):524-31. doi:10.1002/clc.23344.Miao B, Hernandez AV, Roman YM, et al. Four-year incidence of major adverse cardiovascular events in patients with atherosclerosis and atrial fibrillation. Clin Cardiol. 2020;43(5):524-31. doi:10.1002/clc.23344.Gómez-Outes A, Lagunar-Ruíz J, Terleira-Fernández AI, et al. Causes of Death in Anticoagulated Patients with Atrial Fibrillation. J Am Coll Cardiol. 2016;68(23):2508-21. doi:10.1016/j.jacc.2016.09.944.Gómez-Outes A, Lagunar-Ruíz J, Terleira-Fernández AI, et al. Causes of Death in Anticoagulated Patients with Atrial Fibrillation. J Am Coll Cardiol. 2016;68(23):2508-21. doi:10.1016/j.jacc.2016.09.944.Mak KH. Coronary and mortality risk of novel oral antithrombotic agents: a meta-analysis of large randomised trials. BMJ Open. 2012;2(5):e001592. doi:10.1136/bmjopen-2012-001592.Mak KH. Coronary and mortality risk of novel oral antithrombotic agents: a meta-analysis of large randomised trials. BMJ Open. 2012;2(5):e001592. doi:10.1136/bmjopen-2012-001592.Loke YK, Pradhan S, Yeong JK, Kwok CS. Comparative coronary risks of apixaban, rivaroxaban and dabigatran: a meta-analysis and adjusted indirect comparison. Br J Clin Pharmacol. 2014;78(4):707-17. doi:10.1111/bcp.12376.Loke YK, Pradhan S, Yeong JK, Kwok CS. Comparative coronary risks of apixaban, rivaroxaban and dabigatran: a meta-analysis and adjusted indirect comparison. Br J Clin Pharmacol. 2014;78(4):707-17. doi:10.1111/bcp.12376.Tornyos A, Kehl D, D’Ascenzo F, Komócsi A. Risk of Myocardial Infarction in Patients with Long-Term Non-Vitamin K Antagonist Oral Anticoagulant Treatment. Prog Cardiovasc Dis. 2016; 58(5):483-94. doi:10.1016/j.pcad.2015.12.001.Tornyos A, Kehl D, D’Ascenzo F, Komócsi A. Risk of Myocardial Infarction in Patients with Long-Term Non-Vitamin K Antagonist Oral Anticoagulant Treatment. Prog Cardiovasc Dis. 2016; 58(5):483-94. doi:10.1016/j.pcad.2015.12.001.Chatterjee S, Sharma A, Uchino K, et al. Rivaroxaban and risk of myocardial infarction: insights from a meta-analysis and trial sequential analysis of randomized clinical trials. Coron Artery Dis. 2013;24(8):628-35. doi:10.1097/MCA.0000000000000031.Chatterjee S, Sharma A, Uchino K, et al. Rivaroxaban and risk of myocardial infarction: insights from a meta-analysis and trial sequential analysis of randomized clinical trials. Coron Artery Dis. 2013;24(8):628-35. doi:10.1097/MCA.0000000000000031.Hawkins NM, Jhund PS, Pozzi A, et al. Severity of renal impairment in patients with heart failure and atrial fibrillation: implications for non-vitamin K antagonist oral anticoagulant dose adjustment. Eur J Heart Fail. 2016;18(9):1162-71. doi: 10.1002/ejhf.614.Hawkins NM, Jhund PS, Pozzi A, et al. Severity of renal impairment in patients with heart failure and atrial fibrillation: implications for non-vitamin K antagonist oral anticoagulant dose adjustment. Eur J Heart Fail. 2016;18(9):1162-71. doi: 10.1002/ejhf.614.Olesen JB, Lip GY, Kamper AL, et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med. 2012;367(7):625-35. doi:10.1056/NEJMoa1105594. Erratum in: N Engl J Med. 2012;367(23):2262.Olesen JB, Lip GY, Kamper AL, et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med. 2012;367(7):625-35. doi:10.1056/NEJMoa1105594. Erratum in: N Engl J Med. 2012;367(23):2262.Yao X, Tangri N, Gersh BJ, et al. Renal Outcomes in Anti-coagulated Patients with Atrial Fibrillation. J Am Coll Cardiol. 2017;70(21):2621-32. doi:10.1016/j.jacc.2017.09.1087.Yao X, Tangri N, Gersh BJ, et al. Renal Outcomes in Anti-coagulated Patients with Atrial Fibrillation. J Am Coll Cardiol. 2017;70(21):2621-32. doi:10.1016/j.jacc.2017.09.1087.Coleman CI, Kreutz R, Sood NA, et al. Rivaroxaban Versus Warfarin in Patients with Nonvalvular Atrial Fibrillation and Severe Kidney Disease or Undergoing Hemodialysis. Am J Med. 2019;132(9):1078-83. doi:10.1016/j.amjmed.2019.04.013.Coleman CI, Kreutz R, Sood NA, et al. Rivaroxaban Versus Warfarin in Patients with Nonvalvular Atrial Fibrillation and Severe Kidney Disease or Undergoing Hemodialysis. Am J Med. 2019;132(9):1078-83. doi:10.1016/j.amjmed.2019.04.013.Zhang YT, Tang ZY. Research progress of warfarin-associated vascular calcification and its possible therapy. J Cardiovasc Pharmacol. 2014;63(1):76-82. doi:10.1097/FJC.0000000000000008.Zhang YT, Tang ZY. Research progress of warfarin-associated vascular calcification and its possible therapy. J Cardiovasc Pharmacol. 2014;63(1):76-82. doi:10.1097/FJC.0000000000000008.Tantisattamo E, Han KH, O’Neill WC. Increased vascular calcification in patients receiving warfarin. Arterioscler Thromb Vasc Biol. 2015;35(1):237-42. doi:10.1161/ATVBAHA.114.304392.Tantisattamo E, Han KH, O’Neill WC. Increased vascular calcification in patients receiving warfarin. Arterioscler Thromb Vasc Biol. 2015;35(1):237-42. doi:10.1161/ATVBAHA.114.304392.Коваленко Е. А., Боголепова А. Н. Предшествующие инсульту когнитивные нарушения и их влияние на приверженность терапии. Неврология, нейропсихиатрия, психосоматика. 2018;10(2):63-7.Kovalenko EA, Bogolepova AN. Cognitive disorders preceding a stroke and their influence on therapy adherence. Neurology, neuropsychiatry, psychosomatics. 2018;10(2):63-7. (In Russ.)McHorney CA, Peterson ED, Ashton V, et al. Modeling the impact of real-world adherence to once-daily (QD) versus twice-daily (BID) non-vitamin K antagonist oral anticoagulants on stroke and major bleeding events among non-valvular atrial fibrillation patients. Curr Med Res Opin. 2019;35(4):653-60. doi:10.1080/03007995.2018.1530205.McHorney CA, Peterson ED, Ashton V, et al. Modeling the impact of real-world adherence to once-daily (QD) versus twice-daily (BID) non-vitamin K antagonist oral anticoagulants on stroke and major bleeding events among non-valvular atrial fibrillation patients. Curr Med Res Opin. 2019;35(4):653-60. doi:10.1080/03007995.2018.1530205.Kirchhof P, Benussi S, Kotecha D, et al. ESC Scientific Document Group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893-962. doi:10.1093/eurheartj/ehw210.Kirchhof P, Benussi S, Kotecha D, et al. ESC Scientific Document Group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893-962. doi:10.1093/eurheartj/ehw210.Steffel J, Verhamme P, Potpara TS, et al. ESC Scientific Document Group. 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:10.1093/eurheartj/ehy136.Steffel J, Verhamme P, Potpara TS, et al. ESC Scientific Document Group. 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:10.1093/eurheartj/ehy136.González-Fernández M, Ottenstein L, Atanelov L, Christian AB. Dysphagia after Stroke: an Overview. Curr Phys Med Rehabil Rep. 2013;1(3):187-96. doi:10.1007/s40141-013-0017-y.González-Fernández M, Ottenstein L, Atanelov L, Christian AB. Dysphagia after Stroke: an Overview. Curr Phys Med Rehabil Rep. 2013;1(3):187-96. doi:10.1007/s40141-013-0017-y.Instructions for the medical use of the drug Xarelto® 15/20 mg LP-001457. (In Russ.) Инструкция по медицинскому применению лекарственного препарата Ксарелто® 15/20 мг ЛП-001457.Instructions for the medical use of the drug Xarelto® 15/20 mg LP-001457. (In Russ.)

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