Ишемический инсульт и антитромботическая терапия: ключевые аспекты применения

М.Ю. Максимова, e-mail: center@neurology.ru, А.В. Фонякин, e-mail: fonyakin@mail.ru, Л.А. Гераскина, e-mail: neurocor@mail.ru, Научный центр неврологии

В статье рассмотрены стратегические направления антитромботической терапии при ишемическом инсульте. Показано, что антитромботическое лечение данной категории пациентов представляет собой многоступенчатую и мультидисциплинарную проблему, начинающуюся с появления первых неврологических симптомов и продолжающуюся в течение всей последующей жизни. Каждый период, включая темпы доставки больного в стационар, последующие действия медицинского персонала, принятие мер по лечению инсульта, профилактике повторных церебральных нарушений, кардиальных осложнений, важен сам по себе и служит единой цели. В конечном итоге все усилия должны быть направлены на уменьшение летальности в острой фазе инсульта, функциональной зависимости пациента, снижение рецидивов церебрального поражения, неотъемлемое пожизненное следование принципам вторичной профилактики сердечно-сосудистых осложнений для увеличения продолжительности и качества жизни.

Для цитирования: Максимова М.Ю., Фонякин А.В., Гераскина Л.А. Ишемический инсульт и антитромботическая терапия: ключевые аспекты применения. Медицинский Совет. 2019;(18):10-17. https://doi.org/10.21518/2079-701X-2019-18-10-17

Конфликт интересов: авторы заявляют об отсутствии конфликта интересов.

Ischemic stroke and antithrombotic therapy: key aspects

Marina Yu. Maksimova, e-mail: center@neurology.ru, Andrey V. Fonyakin, e-mail: fonyakin@mail.ru, Lyudmila A. Geraskina, e-mail: neurocor@mail.ru, Research Center of Neurology

The paper considers the key areas of antithrombotic therapy for ischemic stroke (IS). Antiplatelet therapy is shown to be a multistage and multidisciplinary strategy of treatment for patients with IS, which begins with the appearance of the first symptoms of the disease and continues throughout life. Each stage, including fibrinolytic therapy, early use of antithrombotic and anticoagulant drugs, and personalized antithrombotic prevention of recurrent cerebral disorders, is important in itself and serves a common goal. As a result, all efforts should be aimed at reducing mortality rates in the acute phase of stroke and the functional dependence of a patient and at preventing venous thromboses, recurrent stroke, and all cardiovascular events to increase life expectancy and to improve quality of life. Fibrinolytic therapy increases the patient’s chances of a full neurologic recovery and improves the quality of later life. Antithrombotic drugs reduce the risk of cardiovascular death, early recurrences of stroke, and recurrent noncardioembolic stroke. Parenteral anticoagulants in acute stroke decrease the risk of venous thrombosis/thromboembolism, oral anticoagulants reduce that of recurrent cardioembolic stroke.

For citation: Maksimova M.Y., Fonyakin A.V., Geraskina L.A. Ischemic stroke and antithrombotic therapy: key aspects. Medical Council. 2019;(18):10-17. (In Russ.) https://doi.org/10.21518/2079-701X-2019-18-10-17

Conflict of interest: The authors declare no conflict of interest.

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Список литературы

1. Пирадов М.А., Танашян М.М., Максимова М.Ю. (ред.). Инсульт: современные технологии диагностики и лечения. М.: МЕДпрессинформ; 2018. 360 с. https://doi.org/10.24421/ МР.2018.18.15909.
2. The European Stroke Organization (ESO) Executive Committee and the ESO Writing Committee: Guidelines for management of ischaemic stroke and transient ischaemic attacks 2008. Cerebrovasc Dis. 2008;25:457507. https://doi.org/10.1159/000131083.
3. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group: Tissue plasminogen activator for acute ischemic stroke. New Engl J Med. 1995;333:1581-1587. https://doi.org/10.1056/ NEJM199512143332401.
4. Powers W.J., Rabinstein A.A., Ackerson T. et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke. A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018;49:e46-e99. https://doi.org/10.1161/STR.0000000000000158.
5. IST-3 collaborative group. Effect of thrombolysis with alteplase within 6 h of acute ischaemic stroke on long-term outcomes (the third International Stroke Trial [IST-3]): 18-month follow-up of a randomised controlled trial. Lancet Neurol. 2013;12(8):768-776. https://doi.org/10.1016/S1474-4422(13)70130-3.
6. Hacke W., Kaste M., Bluhmki E. et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359:1317-1329. https://doi.org/http://dx.doi. org/10.1056/NEJMoa0804656.
7. Del Zoppo G.J., Saver J.L., Jauch E.C., Adams H.P. Jr.; American Heart Association Stroke Council. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/ American Stroke Association. Stroke. 2009;40(8):2945-2948. https://doi.org/10.1161/ STROKEAHA.109.192535.
8. Lees K., Bluhmki E., von Kummer R. et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet. 2010;375:1695-1703. https://doi.org/: 10.1016/S0140-6736(10)60491-6.
9. Пирадов М.А., Домашенко М.А., Максимова М.Ю. Реперфузионные методы лечения ишемического инсульта. В кн.: Пирадов М.А., Иллариошкин С.Н., Танашян М.М. (ред.). Неврология XXI века: диагностические, лечебные и исследовательские технологии: руководство для врачей. Т. II. Высокотехнологичные методы лечения и реабилитации в неврологии. В 3-х т. Москва: АТМО; 2015:9-45.
10. Скворцова В.И., Шетова И.М., Какорина Е.П., Бойко Е.Л., Дашьян В.Г., Крылов В.В. Организация помощи пациентам с инсультом в России. Итоги 10 лет реализации Комплекса мероприятий по совершенствованию медицинской помощи пациентам с острыми нарушениями мозгового кровообращения. Анналы клинической и экспериментальной неврологии 2018;12(3):5-12. https://doi.org/10.25692/ACEN.2018.3.1.
11. Шамалов Н.А. Реперфузионная терапия при ишемическом инсульте в Российской Федерации: проблемы и перспективы. Неврология, нейропсихиатрия, психосоматика. 2011;(спецвыпуск 2):15-21. https://doi.org/10.14412/2074-2711-2014-2S-15-21.
12. Bhatia R., Hill M.D., Shobha N. et al. Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: real-world experience and a call for action. Stroke. 2010;41(10):2254-2258. https://doi.org/10.1161/STROKEAHA.110.592535.
13. Broderick J.P., Palesch Y.Y., Demchuk A.M. et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013;368(10):893-903. https://doi.org/10.1056/ NEJMoa1214300.
14. Riedel C.H., Zimmermann P., Jensen-Kondering U. et al. The importance of size: successful recanalization by intravenous thrombolysis in acute anterior stroke depends on thrombus length. Stroke. 2011;42(6):1775-1777. https://doi.org/10.1161/STROKEAHA.110.609693.
15. Wardlaw J.M., Zoppo G., Yamaguchi T., Berge E. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev. 2003;(3):CD000213. https://doi.org/10.1002/14651858. CD000213.
16. Lansberg M.G., Thijs V.N., Bammer R. et al. Risk factors of symptomatic intracerebral hemorrhage after tPA therapy for acute stroke. Stroke. 2007;38:2275-2278. https://doi.org/10.1161/ STROKEAHA.106.480475.
17. Whiteley W.N., Slot K.B., Fernandes P. et al. Risk factors for intracranial hemorrhage in acute ischemic stroke patients treated with recombinant tissue plasminogen activator: a systematic review and meta-analysis of 55 studies Stroke. 2012;43(11):2904-9. https://doi.org/10.1161/STROKEAHA.112.665331.
18. Домашенко М.А., Максимова М.Ю., Гафарова М.Э. и др. Персонификация подходов к реперфузионной терапии ишемического инсульта. Анналы клинической и экспериментальной неврологии. 2017;11(1):7-13. Режим доступа: http://www.annaly-nevrologii.ru journals/44-tom-11-1-2017.pdf.
19. Alexandrov A.V., Grotta J.C. Arterial reocclusion in stroke patients treated with intravenous tissue plasminogen activator. Neurology. 2002;59(6):862-867. https://doi.org/10.1212/wnl.59.6.862.
20. Rubiera M., Alvarez-Sabín J., Ribo M. et al. Predictors of early arterial reocclusion after tissue plasminogen activator-induced recanalization in acute ischemic stroke. Stroke. 2005;36(7):14521456. https://doi.org/10.1161/01.STR.0000170711.43405.81.
21. Breuer L., Blinzler C., Huttner H.B. et al. Off-label thrombolysis for acute ischemic stroke: rate, clinical outcome and safety are influenced by the definition of ‘minor stroke’. Cerebrovasc Dis. 2011;32(2):177-185. https://doi.org/10.1159/000328811.
22. Guillan M., Alonso-Canovas A., Garcia-Caldentey J. et al. Off-label intravenous thrombolysis in acute stroke. Eur J Neurol. 2012;19(3):390-394. https://doi.org/10.1111/j.1468-1331.2011.03517.
23. Домашенко М.А., Максимова М.Ю., Кистенев Б.А., Лоскутников М.А. и др. Системный медикаментозный тромболизис в острейшем периоде ишемического инсульта. Анналы клинической и экспериментальной неврологии. 2008;2(2):5-12. Режим доступа: https://elibrary.ru/item.asp?id=15130945.
24. Powers W.J., Derdeyn C.P., Jauch E.C. et al. on behalf of the American Heart Association Stroke Council. 2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients with Acute Ischemic Stroke Regarding Endovascular Treatment. A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015;46:3024-3039. https://doi.org/10.1161/ STR.0000000000000074.
25. Binning M.J., Bartolini B., Baxter B. et al. Trevo 2000: Results of a Large Real-World Registry for Stent Retriever for Acute Ischemic Stroke. J Am Heart Assoc. 2018;7:e010867. https://doi.org/10.1161/JAHA.118.010867.
26. CAST (Chinese Acute Stroke Trial) Collaborative Group. CAST: randomized placebo-controlled trial of early aspirin use in 20,000 patients with acute ischemic stroke. Lancet. 1997;349(9066):1641-1649. Available at: https://www.ncbi.nlm.nih.gov/pubmed/9186381.
27. IST (International Stroke Trial) Collaborative Group. The International Stroke Trial (IST): a randomized trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischemic stroke. Lancet. 1997;349(9065):1569-1581. Available at: https://www.ncbi.nlm.nih.gov pubmed/9174558.
28. Chen Z.M., Sandercock 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 Chinese Acute Stroke Trial and the International Stroke Trial. Stroke. 2000;31(6):1240-1249. https://doi.org/10.1161/01.str.31.6.1240.
29. Wang Y., Wang Y., Zhao X. et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369:11-19. https://doi.org/10.1056/NEJMoa1215340.
30. Zuo F.-T., Liu H., Wu H.-J. The effectiveness and safety of dual antiplatelet therapy in ischemic cerebrovascular disease with intracranial and extracranial arteriostenosis in Chinese Patients A randomized and controlled trail. Medicine (Baltimore). 2017;96(1):1-6. https://doi.org/10.1097/MD.0000000000005497 .
31. 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(7329):71-86. https://doi.org/10.1136/bmj.324.7329.71.
32. He J., Whelton P., Vu B., Klag M.J. Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials. JAMA. 1998;280(22):1930-1935. https://doi.org/10.1001/ jama.280.22.1930.
33. CAPRIE Steering Committee. A randomized, blinded trial of clopidogrel versus aspirin in patients at risk of ischemic events (CAPRIE). Lancet. 1996;348(9038):1329-1339. https://doi.org/10.1016/s0140-6736(96)09457-3.
34. Diener H.C., Bogousslavsky J. Brass L.M. et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomized, double-blind, placebo-controlled trial. Lancet. 2004;364:331337. https://doi.org/10.1016/S0140-6736(04)16721-4.
35. Bhatt D.L., Fox K.A.A., Hacke W. et al. CHARISMA investigators: Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354:1706-1717 . https://doi.org/10.1056/NEJMoa060989.
36. SPS3 Investigators; Benavente O.R., Hart R.G., McClure L.A. et al. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med. 2012;367:817-825. https://doi.org/10.1056/NEJMoa1204133.
37. The ESPRIT study group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischemia of arterial origin (ESPRIT): randomized controlled trial. Lancet. 2006;367:16651673. https://doi.org/10.1016/S0140-6736(06)68734-5.
38. Diener H.C., Sacco R.L., Yusuf S., Steering Committee of PROFESS Study Group: Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two Antithrombotic regimen (a fixeddose combination of extended-release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with stroke. The Prevention Regimen for Effectively Avoiding Second Strokes Trial (PROFESS). Cerebrovasc Dis. 2007;23(5-6):368-380. https://doi.org/10.1159/000100105.
39. Costa J., Ferro J.M., Matias-Guiu J. et al. Trifluzal for preventing serious vascular events in people at high risk. Cochrane Database Syst Rev. 2005;(3):CD004296. https://doi.org/10.1002/14651858.CD004296.pub2.
40. Huang Y., Cheng Y., Wu J. et al. Cilostazol as an alternative to aspirin after ischaemic stroke: a randomized double blind pilot study. Lancet Neurol. 2008;7:494-499. https://doi.org/10.1016/S14744422(08)70094-2.
41. Shinohara Y., Katayama Y., Uchiyama S. et al.; CSPS 2 Group. Cilostazol for prevention of secondary stroke (CSPS 2): an aspirin-controlled, double-blind, randomised non-inferiority trial. Lancet Neurol. 2010;9:959-968. https://doi.org/10.1016/S1474-4422(10)70198-8.
42. Shinohara Y., Nishimaru K., Sawada T. et al. Sarpogrelate-aspirin comparative clinical study for efficacy and safety in secondary prevention of cerebral infarction (S-ACCESS). Stroke. 2008;39:1827-1833. https://doi.org/10.1161/ STROKEAHA.107.505131.
43. Johnston S.C., Amarenco P., Albers G.W. et al. Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack. N Engl J Med. 2016;375:35-43. https://doi.org/10.1056/NEJMoa1603060.
44. Amarenco P., Albers G.W., Denison H. et al. Efficacy and safety of ticagrelor versus aspirin in acute stroke or transient ischaemic attack of atherosclerotic origin: a subgroup analysis of SOCRATES, a randomised, double-blind, controlled trial. Lancet Neurol. 2017;16:301310. https://doi.org/10.1016/S1474-4422(17)30038-8.
45. Суслина З.А., Фонякин А.В., Кузнецов А.Л. Кардиоэмболический инсульт: источники эмболии и пути профилактики. Атмосфера. Новости кардиологии. 2004;(2):13-16. Режим доступа: https://elibrary.ru/item. asp?id=24120158.
46. Kernan W.N., Ovbiagele B., Black H.R. et al. Guidelines for the Prevention of Stroke in Patients with Stroke and Transient Ischemic Attack. A Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160-2236. https://doi.org/10.1007/s11940-014-0315-4.
47. Фонякин А.В., Гераскина Л.А. Суслина З.А. (ред.) Профилактика ишемического инсульта. Рекомендации по антитромботи ческой терапии. Москва: ИМА-Пресс; 2014. 72 с.
48. Kirchhof P., Benussi S., Kotecha D. et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893-2962. https://doi.org/10.1093/eurheartj/ehw210.
49. Steffel J., Verhamme P., Potpara T.S. et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation European Heart Journal. 2018;39:1330-1393. https://doi.org/10.1093/eurheartj/ ehy136.
50. 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;38:423-430. https://doi.org/10.1161/01. STR.0000254600.92975.1f.