nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2014-1-48-53nnp-373Research ArticleREVIEWSОБЗОРЫRivaroxaban in secondary prevention of cardioembolic stroke: standards and abnormal situationsРивароксабан во вторичной профилактике кардиоэмболического инсульта: стандарты и нестандартные ситуацииФонякинА.В.FonyakinA.V.1@ru.ruГераскинаЛ.А.GeraskinaL.A.1@ru.ruФГБУ «Научный центр неврологии» РАМН, Москва, РоссияРоссияNeurological Research Center, Russian Academy of Medical Sciences, Moscow, RussiaRussian Federation201406052014614853Copyright © Fonyakin A., Geraskina L., 20142014Фонякин А., Гераскина Л.Fonyakin A., Geraskina L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/373

Possibilities of antithrombotic therapy in prevention of cardioembolic stroke (CES) in patients with nonvalvular atrial fibrillation (AF) were significantly broadened after new oral anticoagulants (NOC) have been designed and launched into clinical practice (rivaroxaban being one of these agents).

In real-life clinical practice, nonvalvular AF can be combined with various cardiovascular pathologies in patients who have had CES, thus giving rise to situations when there are no specific recommendations for NOC.

The article analyzes the most common comorbid clinical situation in vascular neurology and evaluates the potential of rivaroxaban as an alternative to warfarin. Rivaroxaban is shown to be a promising drug for widespread use in angio-neurological practice for treating combined cardiovascular pathology. 

Возможности антитромботической терапии для профилактики кардиоэмболического инсульта (КЭИ) при неклапанной фибрилляции предсердий (ФП) существенно расширились после разработки и внедрения в клиническую практику новых пероральных антикоагулянтов (НОАК), одним из которых является ривароксабан. В реальной клинической практике у пациентов, перенесших КЭИ, неклапанная ФП может сочетаться с различной сердечно-сосудистой патологией, создавая тем самым ситуации, при которых для НОАК конкретные рекомендации не определены. В статье проанализированы наиболее часто встречающиеся в сосудистой неврологии коморбидные клинические ситуации и оценены потенциальные возможности ривароксабана как средства равноценной замены варфарина. Показано, что ривароксабан при сочетанной сердечно-сосудистой патологии имеет хорошие перспективы для широкого применения в ангионеврологической практике. 

кардиоэмболический инсультфибрилляция предсердийривароксабан.cardioembolic strokeatrial fibrillationrivaroxaban.ReferencesВерещагин НВ, Моргунов ВА, Гулевская ТС. Патология головного мозга при атеросклерозе и артериальной гипертонии. Москва: Медицина; 1997. 288 с. [Vereshchagin NV, Morgunov VA, Gulevskaya TS. Patologiya golovnogo mozga pri ateroskleroze i arterial'noi gipertonii [Brain pathology at atherosclerosis and an arterial hypertension]. Moscow: Meditsina; 1997. 288 p.]Верещагин НВ, Моргунов ВА, Гулевская ТС. Патология головного мозга при атеросклерозе и артериальной гипертонии. Москва: Медицина; 1997. 288 с. [Vereshchagin NV, Morgunov VA, Gulevskaya TS. Patologiya golovnogo mozga pri ateroskleroze i arterial'noi gipertonii [Brain pathology at atherosclerosis and an arterial hypertension]. Moscow: Meditsina; 1997. 288 p.]Фонякин АВ, Суслина ЗА, Гераскина ЛА. Кардиальная патология при различных патогенетических подтипах ишемического инсульта. Клиническая медицина. 2002;80(1):25-8. [Fonyakin AV, Suslina ZA, Geraskina LA. Kardialny pathology at various pathogenetic subtypes of an ischemic stroke. Klinicheskaya meditsina. 2002;80(1):25–8. (In Russ.)]Фонякин АВ, Суслина ЗА, Гераскина ЛА. Кардиальная патология при различных патогенетических подтипах ишемического инсульта. Клиническая медицина. 2002;80(1):25-8. [Fonyakin AV, Suslina ZA, Geraskina LA. Kardialny pathology at various pathogenetic subtypes of an ischemic stroke. Klinicheskaya meditsina. 2002;80(1):25–8. (In Russ.)]Cerebral Embolism Task Force. Cardiogenic brain embolism. The second report of the Cerebral Embolism Task Force. Arch Neurol. 1989;46(7):727–43. DOI: http://dx.doi.org/10.1001/arch-neur.1989.00520430021013.Cerebral Embolism Task Force. Cardiogenic brain embolism. The second report of the Cerebral Embolism Task Force. Arch Neurol. 1989;46(7):727–43. DOI: http://dx.doi.org/10.1001/arch-neur.1989.00520430021013.Urbinelli R, Bolard P, Lemesle M, et al. Stroke patterns in cardio-embolic infarction in a population-based study. Neurol Res. 2001;23(4):309–14. DOI: http://dx.doi.org/10.1179/ 016164101101198668.Urbinelli R, Bolard P, Lemesle M, et al. Stroke patterns in cardio-embolic infarction in a population-based study. Neurol Res. 2001;23(4):309–14. DOI: http://dx.doi.org/10.1179/ 016164101101198668.Oppenheimer SM, Lima J. Neurology and the heart. J Neurol Neurosurg Psychiatry. 1998;64(3):289–97. DOI: http://dx.doi.org/10.1136/jnnp.64.3.289.Oppenheimer SM, Lima J. Neurology and the heart. J Neurol Neurosurg Psychiatry. 1998;64(3):289–97. DOI: http://dx.doi.org/10.1136/jnnp.64.3.289.Hanna JP, Furlan AJ. Cardiac disease and embolic sources. In: Brain Ischemia: Basic Concepts and Clinical Relevance. Caplan LR, editor. London; 1995. p. 229–315.Hanna JP, Furlan AJ. Cardiac disease and embolic sources. In: Brain Ischemia: Basic Concepts and Clinical Relevance. Caplan LR, editor. London; 1995. p. 229–315.Суслина ЗА, Фонякин АВ, Петрова ЕА и др. Значение холтеровского мониторирования ЭКГ у больных в остром периоде ишемического инсульта. Терапевтический архив. 1997;69(4):24-6. [Suslina ZA, Fonyakin AV, Petrova EA, et al. Value of holterovsky monitoring of an electrocardiogram at patients in the sharp period of an ischemic stroke. Terapevticheskiky arkhiv. 1997;69(4):24–6. (In Russ.)]Суслина ЗА, Фонякин АВ, Петрова ЕА и др. Значение холтеровского мониторирования ЭКГ у больных в остром периоде ишемического инсульта. Терапевтический архив. 1997;69(4):24-6. [Suslina ZA, Fonyakin AV, Petrova EA, et al. Value of holterovsky monitoring of an electrocardiogram at patients in the sharp period of an ischemic stroke. Terapevticheskiky arkhiv. 1997;69(4):24–6. (In Russ.)]Диагностика и лечение фибрилляции предсердий. Рекомендации РКО, ВНОА и АССХ. Москва; 2012. 112 с. [Diagnostika i lechenie fibrillyatsii predserdii. Rekomendatsii RKO, VNOA i ASSKh [Diagnostics and treatment of fibrillation of auricles. PKO, BHOA and ACCX recommendations]. Moscow; 2012. 112 p.]Диагностика и лечение фибрилляции предсердий. Рекомендации РКО, ВНОА и АССХ. Москва; 2012. 112 с. [Diagnostika i lechenie fibrillyatsii predserdii. Rekomendatsii RKO, VNOA i ASSKh [Diagnostics and treatment of fibrillation of auricles. PKO, BHOA and ACCX recommendations]. Moscow; 2012. 112 p.]Furie KL, Kasner SE, Adams RJ, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack. A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42(1):227–76. DOI:10.1161/STR.0b013e3181f7d043. Epub 2010 Oct 21.Furie KL, Kasner SE, Adams RJ, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack. A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42(1):227–76. DOI:10.1161/STR.0b013e3181f7d043. Epub 2010 Oct 21.Hart RG, Pearce LA, Aguilar MI. Metaanalysis: Antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857–67. DOI: http://dx.doi.org/10.7326/0003-4819-146-12- 200706190-00007.Hart RG, Pearce LA, Aguilar MI. Metaanalysis: Antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857–67. DOI: http://dx.doi.org/10.7326/0003-4819-146-12- 200706190-00007.European Atrial Fibrillation Trial (EAFT) Study Group. Secondary prevention in nonrheumatic atrial fibrillation after transient ischaemic attack or minor stroke. Lancet. 1993;342(8882):1255–62.European Atrial Fibrillation Trial (EAFT) Study Group. Secondary prevention in nonrheumatic atrial fibrillation after transient ischaemic attack or minor stroke. Lancet. 1993;342(8882):1255–62.Baker W, Cios D, Sander S, Coleman CI. Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States. J Manag Care Pharm. 2009;15(3):244–52.Baker W, Cios D, Sander S, Coleman CI. Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States. J Manag Care Pharm. 2009;15(3):244–52.Patel MR, Mahaffey KW, Gard J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:1557–9. DOI: http://dx.doi.org/10.1056/NEJMoa1009638.Patel MR, Mahaffey KW, Gard J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:1557–9. DOI: http://dx.doi.org/10.1056/NEJMoa1009638.Furie KL, Goldstein LB, Albers GW, et al. Oral antithrombotic agents for the prevention of stroke in nonvalvular atrial fibrillation: a science advisory for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43(12):3442–53. DOI: 10.1161/STR.0b013e318266722a. Epub 2012 Aug 2.Furie KL, Goldstein LB, Albers GW, et al. Oral antithrombotic agents for the prevention of stroke in nonvalvular atrial fibrillation: a science advisory for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43(12):3442–53. DOI: 10.1161/STR.0b013e318266722a. Epub 2012 Aug 2.Camm AJ, Lip GYH, De Caterina R, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation. Eur Heart J. 2012;33(21):2719–47. DOI: 10.1093/eurheartj/ehs253. Epub 2012 Aug 24.Camm AJ, Lip GYH, De Caterina R, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation. Eur Heart J. 2012;33(21):2719–47. DOI: 10.1093/eurheartj/ehs253. Epub 2012 Aug 24.Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in atrial fibrillation: a systematic review. Neurology. 2007;69(6):546–54. DOI: http://dx.doi.org/10.1212/01.wnl.0000267275.6 8538.8d.Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in atrial fibrillation: a systematic review. Neurology. 2007;69(6):546–54. DOI: http://dx.doi.org/10.1212/01.wnl.0000267275.6 8538.8d.Palareti G, Cosmi B. Bleeding with anticoagulation therapy – who is at risk, and how best to identify such patients. Thromb Haemost. 2009;102(2):268–78. DOI: 10.1160/TH08-11-0730.Palareti G, Cosmi B. Bleeding with anticoagulation therapy – who is at risk, and how best to identify such patients. Thromb Haemost. 2009;102(2):268–78. DOI: 10.1160/TH08-11-0730.Morocutti C, Amabile G, Fattanpposta F, et al. Indobufen versus warfarin in the secondary prevention of major vascular events in non- rheumatic atrial fibrillation. SIFA (Studio Italiano Fibrillazione Atriale) Investigators.. Stroke. 1997;28(5):1015–21. DOI: http://dx.doi.org/10.1161/01.STR.28.5.1015. 19. Hankey GJ, Patel MR, Stevens SR, et al. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischemic attack: a subgroup analysis of ROCKET AF. Lancet Neurol. 2012;11(4):315–22. DOI: 10.1016/S1474-4422(12)70042-X. Epub 2012 Mar 7.Morocutti C, Amabile G, Fattanpposta F, et al. Indobufen versus warfarin in the secondary prevention of major vascular events in non- rheumatic atrial fibrillation. SIFA (Studio Italiano Fibrillazione Atriale) Investigators.. Stroke. 1997;28(5):1015–21. DOI: http://dx.doi.org/10.1161/01.STR.28.5.1015. 19. Hankey GJ, Patel MR, Stevens SR, et al. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischemic attack: a subgroup analysis of ROCKET AF. Lancet Neurol. 2012;11(4):315–22. DOI: 10.1016/S1474-4422(12)70042-X. Epub 2012 Mar 7.Heidbuchel H, Verhamme P, Alings M, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013;15(5):625–51. DOI: 10.1093/europace/eut083.Heidbuchel H, Verhamme P, Alings M, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013;15(5):625–51. DOI: 10.1093/europace/eut083.Jauch EC, Saver JL, Adams HP, et al. Guidelines for the early management of patients with acute ischemic stroke. Stroke. 2013;44(3):870–947. DOI: 10.1161/STR.0b013e318284056a.Jauch EC, Saver JL, Adams HP, et al. Guidelines for the early management of patients with acute ischemic stroke. Stroke. 2013;44(3):870–947. DOI: 10.1161/STR.0b013e318284056a.Epub 2013 Jan 31.Epub 2013 Jan 31.Granger ChB, Armaganijan LV. Should newer oral anticoagulants be used as first-line agents to prevent thromboembolism in patients with atrial fibrillation and risk factors for stroke or thromboembolism? Circulation. 2012;125(1):159–64. DOI: 10.1161/CIRCULATIONAHA.111.031146.Granger ChB, Armaganijan LV. Should newer oral anticoagulants be used as first-line agents to prevent thromboembolism in patients with atrial fibrillation and risk factors for stroke or thromboembolism? Circulation. 2012;125(1):159–64. DOI: 10.1161/CIRCULATIONAHA.111.031146.Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002;347(13):969–74. DOI: http://dx.doi.org/10.1056/NEJMoa020496.Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002;347(13):969–74. DOI: http://dx.doi.org/10.1056/NEJMoa020496.Mahaffey KW, Stevens SR, White HD, et al. Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial. Eur Heart J. 2014;35(4):233–41. DOI: 10.1093/eurheartj/eht428. Epub 2013 Oct 15.Mahaffey KW, Stevens SR, White HD, et al. Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial. Eur Heart J. 2014;35(4):233–41. DOI: 10.1093/eurheartj/eht428. Epub 2013 Oct 15.Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366(1):9–19. DOI: 10.1056/NEJMoa1112277. Epub 2011 Nov 13.Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366(1):9–19. DOI: 10.1056/NEJMoa1112277. Epub 2011 Nov 13.Lamberts M, Olesen JB, Ruwald MH, et al. Bleeding after initiation of multiple antithrombotic drugs, including triple therapy, in atrial fibrillation patients following myocardial infarction and coronary intervention: a nationwide cohort study. Circulation. 2012;126(10):1185–93. DOI: 10.1161/CIRCULATIONAHA.112.114967. Epub 2012 Aug 6.Lamberts M, Olesen JB, Ruwald MH, et al. Bleeding after initiation of multiple antithrombotic drugs, including triple therapy, in atrial fibrillation patients following myocardial infarction and coronary intervention: a nationwide cohort study. Circulation. 2012;126(10):1185–93. DOI: 10.1161/CIRCULATIONAHA.112.114967. Epub 2012 Aug 6.Sorensen R, Hansen ML, Abildstrom SZ, et al. Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data. Lancet. 2009;374(9706):1967–74. DOI: 10.1016/S0140-6736(09)61751-7.Sorensen R, Hansen ML, Abildstrom SZ, et al. Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data. Lancet. 2009;374(9706):1967–74. DOI: 10.1016/S0140-6736(09)61751-7.Guyatt GH, Akl EA, Crowther M. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST. 2012;141(2 Suppl):7S–47S. DOI: 10.1378/chest.1412S3.Guyatt GH, Akl EA, Crowther M. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST. 2012;141(2 Suppl):7S–47S. DOI: 10.1378/chest.1412S3.Mohr JP, Thompson JL, Lazar RM, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001;345(20):1444–51. DOI: http://dx.doi.org/10.1056/NEJMoa011258.Mohr JP, Thompson JL, Lazar RM, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001;345(20):1444–51. DOI: http://dx.doi.org/10.1056/NEJMoa011258.Liapis CD, Bell PRF, Mikhailidis D, et al. ESVS Guidelines. Invasive treatment for carotid stenosis: indications, techniques. Eur J Vasc Endovasc Surg. 2009;37(4 Suppl):1–19. DOI: 10.1016/j.ejvs.2008.11.006.Liapis CD, Bell PRF, Mikhailidis D, et al. ESVS Guidelines. Invasive treatment for carotid stenosis: indications, techniques. Eur J Vasc Endovasc Surg. 2009;37(4 Suppl):1–19. DOI: 10.1016/j.ejvs.2008.11.006.Фонякин АВ, Гераскина ЛА. Новая эра антикоагулянтной терапии в профилактике инсульта при неревматической фибрилляции предсердий. Неврология, нейропсихиатрия, психосоматика. 2012;(3):15-9. [Fonyakin AV, Geraskina LA. A new era of anticoagulant therapy in the prevention of stroke in non-rheumatic atrial fibrillation. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2012;(3):15–9. (In Russ.)]. DOI: http://dx.doi.org/10.14412/ 2074-2711-2012-396.Фонякин АВ, Гераскина ЛА. Новая эра антикоагулянтной терапии в профилактике инсульта при неревматической фибрилляции предсердий. Неврология, нейропсихиатрия, психосоматика. 2012;(3):15-9. [Fonyakin AV, Geraskina LA. A new era of anticoagulant therapy in the prevention of stroke in non-rheumatic atrial fibrillation. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2012;(3):15–9. (In Russ.)]. DOI: http://dx.doi.org/10.14412/ 2074-2711-2012-396.Гераскина ЛА. Кардиоэмболический инсульт: многообразие причин и современные подходы к профилактике. Неврология, нейропсихиатрия, психосоматика. 2013;(4):60–5. [Geraskina LA. Cardioembolic stroke: a variety of causes and current approaches to its prevention. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2013;(4):60–5. (In Russ.)].Гераскина ЛА. Кардиоэмболический инсульт: многообразие причин и современные подходы к профилактике. Неврология, нейропсихиатрия, психосоматика. 2013;(4):60–5. [Geraskina LA. Cardioembolic stroke: a variety of causes and current approaches to its prevention. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2013;(4):60–5. (In Russ.)].DOI: http://dx.doi.org/10.14412/2074-2711-2013-2457.DOI: http://dx.doi.org/10.14412/2074-2711-2013-2457.

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