clinmedКлиническая медицинаClinical Medicine (Russian Journal)0023-21492412-1339ООО «Медицинское информационное агентство»10.30629/0023-2149-2023-101-7-8-381-386clinmed-594Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL INVESTIGATIONSДлительная антитромбоцитарная терапия у больных с высоким риском инсультаLong-term antiplatelet therapy in patients with high risk of strokehttps://orcid.org/0000-0002-8717-7372ШироковЕ. А.ShirokovE. A.

Широков Евгений Алексеевич — д-р мед. наук, профессор кафедры терапии неотложных состояний 

107392, Москва

 107392, Moscow

evg-74747@yandex.ruФилиал ФГБВОУ ВО Военно-медицинская академия им. С.М. Кирова в г. Москве Минобороны РоссииРоссияBranch Military Medical Academy named after S.M. Kirov in Moscow of the Ministry of Defense of the RussiaRussian Federation2023220920231017-8381386Copyright © Широков Е.А., 20232023Широков Е.А.Shirokov E.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.clinmedjournal.com/jour/article/view/594

Заболевания, ассоциированные с атеросклерозом, занимают ведущее место среди причин смерти в большинстве стран мира. Антитромбоцитарная терапия является одним из эффективных и наиболее перспективных методов профилактики инсульта. Длительное применение тромбоцитарных антиагрегантов различных фармацевтических групп у больных высокого риска стало повседневной клинической практикой. В результате практического применения современных лекарственных стратегий увеличивается продолжительность жизни больных, выживших после инсульта. Увеличивается средний возраст пациентов с сердечно-сосудистой патологией. Большинство больных, получающих антиагреганты, cтарше 70 лет. Количество пациентов, непрерывно получающих антиагреганты в течение 10 и более лет, составляет уже сотни тысяч. В последние годы клинические рекомендации расширили показания для назначения тромбоцитарных антиагрегантов разных фармацевтических групп. В неврологии разрешены клопидогрел, тикагрелор, цилостазол. Однако выбор оптимальной схемы лечения у больных с цереброваскулярной патологией нередко вызывает затруднение у врачей. Стандартные схемы лечения больных с высоким риском инсульта основаны на применении препаратов ацетилсалициловой кислоты. В некоторых случаях больные получают комбинацию антиагрегантов: ацетилсалициловая кислота и дипиридамол. Автор анализирует результаты 30-летнего применения ацетилсалициловой кислоты у больного с высоким риском тромбозов и кровотечений. За этот период больной перенес транзиторную ишемическую атаку, ишемический инсульт, геморроидальные кровотечения и внутричерепное кровоизлияние. В статье на клиническом примере обсуждаются оптимальные решения в выборе антитромботической стратегии у больных с высоким риском инсульта. На основе анализа действующих клинических рекомендаций и научных исследований сформулированы принципы длительной антитромбоцитарной терапии для больных старших возрастных групп при необходимости длительного лечения. Определены основные направления дифференцированной антитромботической терапии в зависимости от предполагаемого патогенетического подтипа ишемического инсульта, риска кровотечений, возраста и предполагаемой продолжительности лечения.

Diseases associated with atherosclerosis occupy a leading place among the causes of death in most countries of the world. Antiplatelet therapy is one of the most eff ective and promising methods of stroke prevention. Long-term use of platelet antiplatelet agents of various pharmaceutical groups in high-risk patients has become a daily clinical practice. As a result of the practical application of modern drug strategies, the life expectancy of stroke survivors is increasing. The average age of patients with cardiovascular pathology is increasing. The majority of patients receiving antiplatelet agents are over 70 years old. The number of patients continuously receiving antiplatelet agents for 10 years or more is already hundreds of thousands. In recent years, clinical guidelines have expanded the indications for the appointment of platelet antiplatelet agents of diff erent pharmaceutical groups. In neurology, clopidogrel, ticagrelor, cilostazol are allowed. However, the choice of the optimal treatment regimen in patients with cerebrovascular pathology often causes diffi culty for doctors. Standard treatment regimens for patients at high risk of stroke are based on the use of acetylsalicylic acid preparations. In some cases, patients receive a combination of antiplatelet agents: aspirin and dipyridamole. The author analyzes the results of 30 years of acetylsalicylic acid use in a patient with a high risk of thrombosis and bleeding. During this period, the patient suff ers a transient ischemic attack, ischemic stroke, hemorrhoidal bleeding and intracranial hemorrhage. The article discusses optimal solutions in choosing an antithrombotic strategy in patients with high risk of stroke on a clinical example. Based on the analysis of current clinical recommendations and scientifi c research, the article formulates the principles of long-term antiplatelet therapy for patients of older age groups with the need for long-term treatment. The main directions of diff erentiated antithrombotic therapy have been determined depending on the suspected pathogenetic subtype of ischemic stroke, the risk of bleeding, age and the expected duration of treatment.

инсультпрофилактика инсультатромбоцитарные антиагрегантыацетилсалициловая кислотаклопидогрелтикагрелорцилостазолдипиридамолstrokestroke preventionplatelet antiplatelet agentsacetylsalicylic acidclopidogrelticagrelorcilostazoldipyridamoleReferencesLi L., Scott C., Rothwell P. Trends in Stroke Incidence in High-Income Countries in the 21st Century Population-Based Study and Systematic Review. Stroke. 2020;51:1372–1380. DOI: 10.1161/STROKEAHA.119.028484Li L., Scott C., Rothwell P. Trends in Stroke Incidence in High-Income Countries in the 21st Century Population-Based Study and Systematic Review. Stroke. 2020;51:1372–1380. DOI: 10.1161/STROKEAHA.119.028484Здравоохранение в России. 2019: Стат.сб./Росстат. М., 2019:170.Здравоохранение в России. 2019: Стат.сб./Росстат. М., 2019:170. [Healthcare in Russia. 2019: Stat.sb./ М., 2019:170. (In Russian).Visseren F.L.J., et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur. Heart J. 2021;42(34):3227– 3337. DOI: 10.1093/eurheartj/ehab484Visseren F.L.J., et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur. Heart J. 2021;42(34):3227– 3337. DOI: 10.1093/eurheartj/ehab484Суслина З.А., Танашян М.М., Домашенко М.А. Индивидуали зация антиагрегантной терапии у пациентов с цереброваскулярными заболеваниями. Клиническая фармакология и терапия. 2011;5:70–74.Suslina Z.A., Tanashyan M.M., Doma shenko M.A. Individualization of antiplatelet therapy in patients with cerebrovascular diseases. Clinical pharmacology and therapy. 2011;5:70–74. (In Russian).SCORE2 working group and ESC Cardiovascular risk collaboration. SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. European Heart Journal. 2021;42(25):2439–2454. DOI: 10.1093/eurheart/ehab309SCORE2 working group and ESC Cardiovascular risk collaboration. SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. European Heart Journal. 2021;42(25):2439–2454. DOI: 10.1093/eurheart/ehab309Клинические рекомендации по ведению больных с ишемическим инсультом и транзиторными ишемическими атаками / под ред. проф. Л.В.Стаховской. М., 2017:208.Clinical recommendations for the management of patients with ischemic stroke and transient ischemic attacks / edited by prof. L.V. Stakhovskaya. M., 2017:208. (In Russian).Сумароков А.Б., Широков Е.А., Бурячковская Л.И. Антитромбоцитарная терапия в профилактике ишемического некардиоэмболического инсульта. Основные положения современных рекомендаций. Москва, 2015:34.Sumarokov A.B., Shirokov E.A., Buryachkovskaya L.I. Antiplatelet therapy in the prevention of ischemic noncardioembolic stroke. The main provisions of modern recommendations. Moscow, 2015:34. (In Russian).Мачинский П.А., Плотникова Н.А., Ульянкин В.Е. с соавт. Сравнительная характеристика показателей заболеваемости ишемическим и геморрагическим инсультом в России. Медицинские науки. Патологическая анатомия. 2019;2(50):112–131. DOI: 10.21685/2072-3032-2019-2-11Machinsky P.A., Plotnikova N.A., Ulyankin V.E. et al. Comparative characteristics of the incidence of ischemic and hemorrhagic stroke in Russia. Medical sciences. Pathological anatomy. 2019;2(50):112– 131. (In Russian). DOI: 10.21685/2072-3032-2019-2-11Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomized trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324:71–86.Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomized trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324:71–86.Li L., Geraghty O., Mehta Z. et al. Age-specifi c risk, severity, timecoruse, and outcome of bleeding on long-timing antiplatelet treatment basded cohort study. Lancet. 2017;29;390(10093):490–499.Li L., Geraghty O., Mehta Z. et al. Age-specifi c risk, severity, timecoruse, and outcome of bleeding on long-timing antiplatelet treatment basded cohort study. Lancet. 2017;29;390(10093):490–499.Бурячковская Л. И., Ломакин Н. В., Сумароков А. Б., Доценко Ю.В. Значение особенностей действия антиагрегантов для выбора терапии сосудистого больного. Тромбоз, гемостаз и реология. 2017;4(72):6–13. DOI:10.25555/THR.2017.4.0803Bu ryach kovskaya L. I., Lomakin N. V., Sumarokov A. B., Dotsenko Yu.V. The signifi cance of the features of the action of antiplatelet agents for the choice of therapy of a vascular patient. Thrombosis, hemostasis and rheology. 2017;4(72):6–13. (In Russian). DOI:10.25555/THR.2017.4.0803Diener H.C., Sacco R., Yusuf S.; PRoFESS Study Group. Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic regimens (a fi xed-dose combination of extended-release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: the Prevention Regimen for Eff ectively Avoiding Second Strokes trial (PRoFESS). Cerebrovasc. Dis. 2007;23:368–80.Diener H.C., Sacco R., Yusuf S.; PRoFESS Study Group. Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic regimens (a fixed-dose combination of extended-release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: the Prevention Regimen for Eff ectively Avoiding Second Strokes trial (PRoFESS). Cerebrovasc. Dis. 2007;23:368–80.McHutchison C., Blair G.W., MRCP; Appleton J.P. et al. Cilostazol for Secondary Prevention of Stroke and Cognitive Decline. Systematic Review and Meta-Analysis. Stroke. 2020;51:2374–2385. DOI: 10.1161/STROKEAHA.120.029454McHutchison C., Blair G.W., MRCP; Appleton J.P. et al. Cilostazol for Secondary Prevention of Stroke and Cognitive Decline. Systematic Review and Meta-Analysis. Stroke. 2020;51:2374–2385. DOI: 10.1161/STROKEAHA.120.029454Ломакин Н.В., Сумароков А.Б., Доценко Ю.В. с соавт. Индивидуальный подход к применению антитромбоцитарной терапии. На что опереться в решении? Атеротромбоз. 2017;2:70–78.Lo makin N.V., Sumarokov A.B., Dotsenko Yu.V. et al. Individual approach to the use of antiplatelet therapy. What to rely on in the decision? Atherothrombosis. 2017;2:70–78. (In Russian).Kennedy J., Ryckborst K., et al. for the FASTER investigators: Fast Assessment of Stroke and Transient Ischemic Attack to prevent Early Recurrence (FASTER): a randomized controlled pilot trial. Lancet Neurol. 2007;6:961–969.Kennedy J., Ryckborst K., et al. for the FASTER investigators: Fast Assessment of Stroke and Transient Ischemic Attack to prevent Early Recurrence (FASTER): a randomized controlled pilot trial. Lancet Neurol. 2007;6:961–969.CAPRIE Steering Committee. A randomized, blinded, trial of Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE). Lancet. 1996;348:1329–1339.CAPRIE Steering Committee. A randomized, blinded, trial of Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE). Lancet. 1996;348:1329–1339.Greving J.P., Diener H., Reitsma J.B. et al. Antiplatelet Therapy After Noncardioembolic Stroke. Stroke. 2019;50(7):1812–1818. DOI: 10.1161/STROKEAHA.118.024497Greving J.P., Diener H., Reitsma J.B. et al. Antiplatelet Therapy After Noncardioembolic Stroke. Stroke. 2019;50(7):1812–1818. DOI: 10.1161/STROKEAHA.118.024497Li Z., Wang Y., Zhao X. et al. Treatment eff ect of clopidogrel plus aspirin within 12 hours of acute minor stroke or transient ischemic attack. J. Am. Heart Assoc. 2016;5:e003038. DOI: 10/1161/JAHA.115.003038Li Z., Wang Y., Zhao X. et al. Treatment eff ect of clopidogrel plus aspirin within 12 hours of acute minor stroke or transient ischemic attack. J. Am. Heart Assoc. 2016;5:e003038. DOI: 10/1161/JAHA.115.003038Широков Е.А., Симоненко В.Б., Овчинников Ю.В. Транзиторные ишемические атаки и малые инсульты: современные тера певтические стратегии. Лечащий врач. 2020;5:7–11.Shirokov E.A., Simonenko V.B., Ovchinnikov Yu.V. Transient ischemic attacks and small strokes: modern therapeutic strategies. Lechasyi vrach. 2020;5:7–11. (In Russian).Wang Y., Meng A., Wang A. et al. Ticagrelor versus Clopidogrel in CYP2C19 Loss-of Function Carries with Stroke or TIA. N. Engl. J. Med. 2021. DOI: 10/1056/NEJMoa2111749. Online ahead of primt.Wang Y., Meng A., Wang A. et al. Ticagrelor versus Clopidogrel in CYP2C19 Loss-of Function Carries with Stroke or TIA. N. Engl. J. Med. 2021. DOI: 10/1056/NEJMoa2111749. Online ahead of primt.Uchiyama S., Amarenco P. et al. TIA as acute cerebrovascular syndrome. Front Neurol Neurosci. 2014;33:135–146.Uchiyama S., Amarenco P. et al. TIA as acute cerebrovascular syndrome. Front Neurol Neurosci. 2014;33:135–146.Johnston S.C., Amarenco P., Denison H. et al. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. N. Engl. J. Med. 2020;383:207–217.Johnston S.C., Amarenco P., Denison H. et al. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. N. Engl. J. Med. 2020;383:207–217.Shaban A., Monlezun D.J., Rincon N. et al. Safety and effi cacy of acute clopidogrel load in patients with moderate and severe ischemic strokes. Stroke Research and Treatment. 2016;2016:8915764. DOI: 10/1155/2016/8915764Shaban A., Monlezun D.J., Rincon N. et al. Safety and effi cacy of acute clopidogrel load in patients with moderate and severe ischemic strokes. Stroke Research and Treatment. 2016;2016:8915764. DOI: 10/1155/2016/8915764Balint A., Tornios D., Alaoui O. et al. Network Meta-Analis of Ticagrelor for Stroke prevention in patients at High Risk for Cardiovascular or Cerebrovascular Events. Stroke. 2021;52(9):2809–2816.Balint A., Tornios D., Alaoui O. et al. Network Meta-Analis of Ticagrelor for Stroke prevention in patients at High Risk for Cardiovascular or Cerebrovascular Events. Stroke. 2021;52(9):2809–2816.Chen Z.M., Sandercoch P., Pan H.C. et al. Indication for early aspirin use in acute ischemic stroke. A combined analysis of 40 000 randomized patients from the Chines Acute Stroke Trial and the International Stroke Trial. Stroke. 2000;31:1240–1249.Chen Z.M., Sandercoch P., Pan H.C. et al. Indication for early aspirin use in acute ischemic stroke. A combined analysis of 40 000 randomized patients from the Chines Acute Stroke Trial and the International Stroke Trial. Stroke. 2000;31:1240–1249.Rothwell P., Algra A., Chen Z. Eff ects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials. Lancet. 2016;388(10042):365–375. DOI: 10.1016/S0140-6736(16)30468-8Rothwell P., Algra A., Chen Z. Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials. Lancet. 2016;388(10042):365–375. DOI: 10.1016/S0140-6736(16)30468-8Uchiyama S., Toyoda K., Omae K. et al. Dual Antiplatelet Therapy Using Cilostazol in Patients With Stroke and Intracranial Arterial Stenosis. Journal of the American Heart Association. 2021;10(20):19. DOI: 10.1161/JAHA.121.022575Uchiyama S., Toyoda K., Omae K. et al. Dual Antiplatelet Therapy Using Cilostazol in Patients With Stroke and Intracranial Arterial Stenosis. Journal of the American Heart Association. 2021;10(20):19. DOI: 10.1161/JAHA.121.022575Zurrú M., Orzuza C. Epidemiological Aspects of Stroke in Very Old Patients. Cardiovascular and Haematological Disorders-Drug Targets. 2011;11(1):3–5.Zurrú M., Orzuza C. Epidemiological Aspects of Stroke in Very Old Patients. Cardiovascular and Haematological Disorders-Drug Targets. 2011;11(1):3–5.Niu P.P., Guo Z.N., Jin H. et al. Antiplatelet regimens in the longterm secondary prevention of transient ischaemic attack and ischaemic stroke: an updated network meta-analysis. BMJ Open. 2016;6: e009013. DOI: 10.1136/bmjopen-2015-009013Niu P.P., Guo Z.N., Jin H. et al. Antiplatelet regimens in the longterm secondary prevention of transient ischaemic attack and ischaemic stroke: an updated network meta-analysis. BMJ Open. 2016;6: e009013. DOI: 10.1136/bmjopen-2015-009013RESTART Collaboration. Eff ects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial. Published Online. 2019. DOI: 10.1016/S0140-6736(19)30840-2RESTART Collaboration. Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial. Published Online. 2019. DOI: 10.1016/S0140-6736(19)308402The Publications Committee for the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. Low molecular weight heparinoid, ORG 10172 (danaparoid), and outcome after acute ischemic stroke: a randomized controlled trial. JAMA. 1998;279:1265– 1272.The Publications Committee for the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. Low molecular weight heparinoid, ORG 10172 (danaparoid), and outcome after acute ischemic stroke: a randomized controlled trial. JAMA. 1998;279:1265– 1272.Waters M., Hoh B., Lynn N. et al. Factors associated with recurrent stroke in the medical group of the SAMMPRIS trial. JAMA Neurol. 2016;73(3):308–315. DOI: 10,1001/jamaneurol.2015.4315Waters M., Hoh B., Lynn N. et al. Factors associated with recurrent stroke in the medical group of the SAMMPRIS trial. JAMA Neurol. 2016;73(3):308–315. DOI: 10,1001/jamaneurol.2015.4315

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