nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2021-5-14-19nnp-1660Research ArticleLECTURESЛЕКЦИЯAntiplatelet therapy in stroke prevention after non-cardioembolic transient ischemic attackАнтитромбоцитарная терапия в профилактике инсульта после транзиторной ишемической атаки некардиоэмболического генезаФонякинА. В.FonyakinA. V.

Андрей Викторович Фонякин

2-е неврологическое отделение

125367, Москва, Волоколамское шоссе, 80

Andrey Viktorovich Fonyakin

Second Neurological Department

80, Volokolamskoe Shosse, Moscow 125367

fonyakin@mail.ruГераскинаЛ. А.GeraskinaL. A.

2-е неврологическое отделение

125367, Москва, Волоколамское шоссе, 80

Second Neurological Department

80, Volokolamskoe Shosse, Moscow 125367

МаксимоваМ. Ю.MaksimovaM. Yu.

2-е неврологическое отделение

125367, Москва, Волоколамское шоссе, 80

Second Neurological Department

80, Volokolamskoe Shosse, Moscow 125367

ФГБНУ «Научный центр неврологии»РоссияResearch Center of NeurologyRussian Federation2021161020211351419Copyright © Fonyakin A.V., Geraskina L.A., Maksimova M.Y., 20212021Фонякин А.В., Гераскина Л.А., Максимова М.Ю.Fonyakin A.V., Geraskina L.A., Maksimova M.Y.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/1660

The review shows modern concepts on the role of antiplatelet therapy in the secondary prevention of cardiovascular diseases in patients after non-cardioembolic ischemic stroke or transient ischemic attack (TIA). We present an analytical characteristic of all antiplatelet agents that have been studied in randomized controlled trials worldwide. We demonstrate the advantages and disadvantages of each agent in monotherapy and in combination. New ideas about the rationality of the use of combined antiplatelet therapy with clopidogrel and acetylsalicylic acid in the first 24 hours and no more than 90 days in patients with minor ischemic stroke or TIA are discussed. The efficacy and safety of new antiplatelet agents are analyzed. The basic principles of choosing antiplatelet agents in patients after ischemic noncardioembolic stroke/TIA are outlined.

В статье показаны современные представления о роли антитромбоцитарной терапии во вторичной профилактике сердечно-сосудистых заболеваний у пациентов, перенесших некардиоэмболический ишемический инсульт либо транзиторную ишемическую атаку (ТИА). На основе данных доказательной медицины представлена аналитическая характеристика всех тромбоцитарных антиагрегантов, прошедших клинические испытания в мире. Продемонстрированы преимущества и несовершенства каждого средства как в монотерапии, так и при комбинированном использовании. Отражены новые представления о рациональности применения комбинированной антитромбоцитарной терапии клопидогрелом и ацетилсалициловой кислотой в первые 24 ч и продолжительностью не более 90 дней у больных с малым ишемическим инсультом либо ТИА. Анализируются эффективность и безопасность новых тромбоцитарных антиагрегантов. Изложены основные принципы выбора антитромбоцитарных средств у пациентов после ишемического некардиоэмболического инсульта.

антитромбоцитарная терапиятранзиторная ишемическая атаканекардиоэмболический инсультвторичная профилактикаantiplatelet therapytransient ischemic attacknoncardioembolic strokesecondary preventionReferencesEaston JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. Stroke. 2009 Jun;40(6):2276-93. doi: 10.1161/STROKEAHA.108.192218. Epub 2009 May 7.Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. Stroke. 2009 Jun;40(6):2276-93. doi: 10.1161/STROKEAHA.108.192218. Epub 2009 May 7.Стаховская ЛВ, редактор. Клинические рекомендации по ведению больных с ишемическим инсультом и транзиторными ишемическими атаками. Москва: МЕДпресс-информ; 2017. 208 с.Stakhovskaya LV, editor. Klinicheskiye rekomendatsii po vedeniyu bol'nykh s ishemicheskim insul'tom i tranzitornymi ishemicheskimi atakami [Clinical guidelines for the management of patients with ischemic stroke and transient ischemic attacks]. Moscow: MEDpressinform; 2017. 208 p. (In Russ.).Johnston SC, Gress DR, Browner WS, Sidney S. Short-term prognosis after emergency department diagnosis of transient ischemic attack. JAMA. 2000 Dec 13;284(22):2901-6. doi: 10.1001/jama.284.22.2901Johnston SC, Gress DR, Browner WS, Sidney S. Short-term prognosis after emergency department diagnosis of transient ischemic attack. JAMA. 2000 Dec 13;284(22):2901-6. doi: 10.1001/jama.284.22.2901Johnston SC, Nguyen-Huynh MN, Schwarz ME, et al. National Stroke Association guidelines for the management of transient ischemic attacks. Ann Neurol. 2006 Sep;60(3):301-13. doi: 10.1002/ana.20942Johnston SC, Nguyen-Huynh MN, Schwarz ME, et al. National Stroke Association guidelines for the management of transient ischemic attacks. Ann Neurol. 2006 Sep;60(3):301-13. doi: 10.1002/ana.20942European Stroke Organisation (ESO) Executive Committee; ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis. 2008;25(5):457-507. doi: 10.1159/000131083. Epub 2008 May 6.European Stroke Organisation (ESO) Executive Committee; ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis. 2008;25(5):457-507. doi: 10.1159/000131083. Epub 2008 May 6.Гераскина ЛА, Фонякин АВ. Транзиторные ишемические атаки. Современный взгляд на актуальную проблему. Трудный пациент. 2011;(5):28-32.Geraskina LA, Fonyakin AV. Transient ischemic attacks. A modern view of the current problem. Trudnyy patsiyent. 2011;(5):28-32 (In Russ.).Rothwell PM, Giles MF, Flossmann E, et al. A simple score (ABCD) to identify individuals at high early risk of stroke after transient ischaemic attack. Lancet. 2005 Jul 2-8;366(9479):29-36. doi: 10.1016/S0140-6736(05)66702-5Rothwell PM, Giles MF, Flossmann E, et al. A simple score (ABCD) to identify individuals at high early risk of stroke after transient ischaemic attack. Lancet. 2005 Jul 2-8;366(9479):29-36. doi: 10.1016/S0140-6736(05)66702-5Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007 Jan 27;369(9558):283-92. doi: 10.1016/S0140-6736(07)60150-0Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007 Jan 27;369(9558):283-92. doi: 10.1016/S0140-6736(07)60150-0Powers WJ, Rabinstein AA, 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 Mar;49(3):e46-e110. doi: 10.1161/STR.0000000000000158. Epub 2018 Jan 24.Powers WJ, Rabinstein AA, 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 Mar;49(3):e46-e110. doi: 10.1161/STR.0000000000000158. Epub 2018 Jan 24.Суслина ЗА, Фонякин АВ, Кузнецов АЛ. Кардиоэмболический инсульт: источники эмболии и пути профилактики. Атмосфера. Новости кардиологии. 2004;(2):13-6.Suslina ZA, Fonyakin AV, Kuznetsov AL. Cardioembolic stroke: sources of embolism and ways of prevention. Atmosfera. Novosti kardiologii. 2004;(2):13-6 (In Russ.).Purroy F, Montaner J, Molina CA, et al. Patterns and predictors of early risk of recurrence after transient ischemic attack with respect to etiologic subtypes. Stroke. 2007 Dec;38(12):3225-9. doi: 10.1161/STROKEAHA.107.488833Purroy F, Montaner J, Molina CA, et al. Patterns and predictors of early risk of recurrence after transient ischemic attack with respect to etiologic subtypes. Stroke. 2007 Dec;38(12):3225-9. doi: 10.1161/STROKEAHA.107.488833Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2021 Jul;52(7):e364-e467. doi: 10.1161/STR.0000000000000375Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2021 Jul;52(7):e364-e467. doi: 10.1161/STR.0000000000000375Naqvi IA, Kamal AK, Rehman H. Multiple versus fewer antiplatelet agents for preventing early recurrence after ischaemic stroke or transient ischaemic attack. Cochrane Database Syst Rev. 2020 Aug 17;8(8):CD009716. doi: 10.1002/14651858.CD009716.pub2Naqvi IA, Kamal AK, Rehman H. Multiple versus fewer antiplatelet agents for preventing early recurrence after ischaemic stroke or transient ischaemic attack. Cochrane Database Syst Rev. 2020 Aug 17;8(8):CD009716. doi: 10.1002/14651858.CD009716.pub2Chimowitz MI, Lynn MJ, Howlett-Smith H, et al; Warfarin-Aspirin Symptomatic Intracranial Disease Trial Investigators. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med. 2005 Mar 31;352(13):1305-16. doi: 10.1056/NEJMoa043033Chimowitz MI, Lynn MJ, Howlett-Smith H, et al; Warfarin-Aspirin Symptomatic Intracranial Disease Trial Investigators. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med. 2005 Mar 31;352(13):1305-16. doi: 10.1056/NEJMoa043033Chimowitz MI, Lynn MJ, Derdeyn CP, et al; SAMMPRIS Trial Investigators. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011 Sep 15;365(11):993-1003. doi: 10.1056/NEJMoa1105335. Epub 2011 Sep 7.Chimowitz MI, Lynn MJ, Derdeyn CP, et al; SAMMPRIS Trial Investigators. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011 Sep 15;365(11):993-1003. doi: 10.1056/NEJMoa1105335. Epub 2011 Sep 7.Collaborative overview of randomised trials of antiplatelet therapy: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. BMJ. 1994 Jan 8;308(6921):81-106.Collaborative overview of randomised trials of antiplatelet therapy: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. BMJ. 1994 Jan 8;308(6921):81-106.Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002 Jan 12;324(7329):71-86. doi: 10.1136/bmj.324.7329.71Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002 Jan 12;324(7329):71-86. doi: 10.1136/bmj.324.7329.71He J, Whelton P, Vu B, Klag MJ. Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials. JAMA. 1998 Dec 9;280(22):1930-5. doi: 10.1001/jama.280.22.1930He J, Whelton P, Vu B, Klag MJ. Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials. JAMA. 1998 Dec 9;280(22):1930-5. doi: 10.1001/jama.280.22.1930Johnston SC, Amarenco P, Albers GW, et al. Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack. N Engl J Med. 2016 Jul 7;375(1):35-43. doi: 10.1056/NEJMoa1603060. Epub 2016 May 10.Johnston SC, Amarenco P, Albers GW, et al. Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack. N Engl J Med. 2016 Jul 7;375(1):35-43. doi: 10.1056/NEJMoa1603060. Epub 2016 May 10.Amarenco P, Albers GW, 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;16:301-10. doi: 10.1016/S1474-4422(17)30038-8Amarenco P, Albers GW, 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;16:301-10. doi: 10.1016/S1474-4422(17)30038-8CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996 Nov 16;348(9038):1329-39. doi: 10.1016/s0140-6736(96)09457-3CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996 Nov 16;348(9038):1329-39. doi: 10.1016/s0140-6736(96)09457-3Costa J, Ferro JM, Matias-Guiu J, et al. Trifluzal for preventing serious vascular events in people at high risk. Stroke. 2005 Jul 20;(3):CD004296. doi: 10.1002/14651858.CD004296.pub2Costa J, Ferro JM, Matias-Guiu J, et al. Trifluzal for preventing serious vascular events in people at high risk. Stroke. 2005 Jul 20;(3):CD004296. doi: 10.1002/14651858.CD004296.pub2Huang 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 Jun;7(6):494-9. doi: 10.1016/S1474-4422(08)70094-2. Epub 2008 May 2.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 Jun;7(6):494-9. doi: 10.1016/S1474-4422(08)70094-2. Epub 2008 May 2.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 Jun;39(6):1827-33. doi: 10.1161/STROKEAHA.107.505131. Epub 2008 Apr 3.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 Jun;39(6):1827-33. doi: 10.1161/STROKEAHA.107.505131. Epub 2008 Apr 3.Kennedy J, Ryckborst KJ, Eliasziw M, et al. Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomized controlled pilot trial. Lancet Neurol. 2007 Nov;6(11):961-9. doi: 10.1016/S1474-4422(07)70250-8. Epub 2007 Oct 10.Kennedy J, Ryckborst KJ, Eliasziw M, et al. Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomized controlled pilot trial. Lancet Neurol. 2007 Nov;6(11):961-9. doi: 10.1016/S1474-4422(07)70250-8. Epub 2007 Oct 10.Rothwell PM, Giles MF, Chandratheva A, et al. Effect of urgent treatment of transient ischemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. Lancet. 2007 Oct 20;370(9596):1432-42. doi: 10.1016/S0140-6736(07)61448-2Rothwell PM, Giles MF, Chandratheva A, et al. Effect of urgent treatment of transient ischemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. Lancet. 2007 Oct 20;370(9596):1432-42. doi: 10.1016/S0140-6736(07)61448-2Танашян ММ, Домашенко МА. Применение курантила при цереброваскулярных заболеваниях. Атмосфера. Нервные болезни. 2005;(3):8-11.Tanashyan MM, Domashenko MA. The use of curantile for cerebrovascular diseases. Atmosfera. Nervnyye bolezni. 2005;(3):8-11 (In Russ.).Diener HC, Cunha L, Forbes C, et al. European Stroke Prevention Study 2 (ESPS2). Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996 Nov;143(1-2):1-13. doi: 10.1016/s0022-510x(96)00308-5Diener HC, Cunha L, Forbes C, et al. European Stroke Prevention Study 2 (ESPS2). Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996 Nov;143(1-2):1-13. doi: 10.1016/s0022-510x(96)00308-5ESPRIT Study Group, Halkes PH, van Gijn J, Kappelle LJ, et al. Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial. Lancet Neurol. 2007 Feb;6(2):115-24. doi: 10.1016/S1474-4422(06)70685-8ESPRIT Study Group, Halkes PH, van Gijn J, Kappelle LJ, et al. Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial. Lancet Neurol. 2007 Feb;6(2):115-24. doi: 10.1016/S1474-4422(06)70685-8Verro P, Gorelick PB, Nguyen D. Aspirin plus dipyridamole versus aspirin for prevention of vascular events after stroke or TIA: a metaanalysis. Stroke. 2008;39(4):1358-63. doi: 10.1161/STROKEAHA.107.496281Verro P, Gorelick PB, Nguyen D. Aspirin plus dipyridamole versus aspirin for prevention of vascular events after stroke or TIA: a metaanalysis. Stroke. 2008;39(4):1358-63. doi: 10.1161/STROKEAHA.107.496281Guiraud-Chaumeil B, Rascol A, David J, et al. Prevention des recidives des accidents vasculaires cerebraux ischemiques par les antiagregants plaquettaires: resultants d'un essai therapique controle de 3 ans. Rev Neurol. 1982;138(5):367-85.Guiraud-Chaumeil B, Rascol A, David J, et al. Prevention des recidives des accidents vasculaires cerebraux ischemiques par les antiagregants plaquettaires: resultants d'un essai therapique controle de 3 ans. Rev Neurol. 1982;138(5):367-85.Bousser MG, Eschwege E, Haguenau M, et al. «AICLA» controlled trial of aspirin and dipyridamole in the secondary prevention of atherothrombotic cerebral ischemia. Stroke. Jan-Feb 1983;14(1):5-14. doi: 10.1161/01.str.14.1.5Bousser MG, Eschwege E, Haguenau M, et al. «AICLA» controlled trial of aspirin and dipyridamole in the secondary prevention of atherothrombotic cerebral ischemia. Stroke. Jan-Feb 1983;14(1):5-14. doi: 10.1161/01.str.14.1.5American-Canadian Cooperative Study Group. Persantine aspirin trial in cerebral ischemia, part II: endpoint results. Stroke. May-Jun 1985;16(3):406-15. doi: 10.1161/01.str.16.3.406American-Canadian Cooperative Study Group. Persantine aspirin trial in cerebral ischemia, part II: endpoint results. Stroke. May-Jun 1985;16(3):406-15. doi: 10.1161/01.str.16.3.406Johnston SC, Easton JD, Farrant M, et al.; Clinical Research Collaboration, Neurological Emergencies Treatment Trials Network, and the POINT Investigators. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med. 2018 Jul 19;379(3):215-25. doi: 10.1056/NEJMoa1800410. Epub 2018 May 16.Johnston SC, Easton JD, Farrant M, et al.; Clinical Research Collaboration, Neurological Emergencies Treatment Trials Network, and the POINT Investigators. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med. 2018 Jul 19;379(3):215-25. doi: 10.1056/NEJMoa1800410. Epub 2018 May 16.Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013 Jul 4;369(1):11-9. doi: 10.1056/NEJMoa1215340. Epub 2013 Jun 26.Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013 Jul 4;369(1):11-9. doi: 10.1056/NEJMoa1215340. Epub 2013 Jun 26.Ge F, Lin H, Liu Y, et al. Dual antiplatelet therapy after stroke or transient ischaemic attack – how long to treat? The duration of aspirin plus clopidogrel in stroke or transient ischaemic attack: a systematic review and meta-analysis. Eur J Neurol. 2016 Jun;23(6):1051-7. doi: 10.1111/ene.12982. Epub 2016 Mar 28.Ge F, Lin H, Liu Y, et al. Dual antiplatelet therapy after stroke or transient ischaemic attack – how long to treat? The duration of aspirin plus clopidogrel in stroke or transient ischaemic attack: a systematic review and meta-analysis. Eur J Neurol. 2016 Jun;23(6):1051-7. doi: 10.1111/ene.12982. Epub 2016 Mar 28.Johnston SC, Amarenco P, Denison H, et al; THALES Investigators. Ticagrelor and aspirin or aspirin alone in acute ischemic stroke or TIA. N Engl J Med. 2020 Jul 16;383(3):207-17. doi: 10.1056/NEJMoa1916870Johnston SC, Amarenco P, Denison H, et al; THALES Investigators. Ticagrelor and aspirin or aspirin alone in acute ischemic stroke or TIA. N Engl J Med. 2020 Jul 16;383(3):207-17. doi: 10.1056/NEJMoa1916870

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