PharmatecaPharmatecaФарматека2073-40342414-9128Bionika Media67998210.18565/pharmateca.2024.9.70-77NeurologyНеврологияResearch ArticleFeatures of alteplase reperfusion therapy in the treatment of ischemic stroke and acute coronary syndromeОсобенности реперфузионной терапии алтеплазой в лечении ишемического инсульта и острого коронарного синдромаhttps://orcid.org/0000-0002-6485-1061SafiullinaZ. M.СафиуллинаЗ. М.
Russian Federation

Dr. Sci. (Med.), Professor, Department of Cardiology and Cardiac Surgery with the Course of Emergency Medical Care

д.м.н., профессор кафедры кардиологии и кардиохирургии с курсом СМП института клинической медицины

safiullina@tokb.ruhttps://orcid.org/0000-0002-6086-4578MezhonovE. M.МежоновЕ. М.
Russian Federation
safiullina@tokb.ruhttps://orcid.org/0000-0001-6470-5606VyalkinaYu. A.ВялкинаЮ. А.
Russian Federation
safiullina@tokb.ruhttps://orcid.org/0000-0003-2724-4016ShalaevS. V.ШалаевС. В.
Russian Federation
safiullina@tokb.ruTyumen State Medical UniversityТюменский государственный медицинский университетRegional Clinical Hospital No. 1Областная клиническая больница № 12012202431970771905202519052025Copyright ©; 2024, Bionika MediaCopyright ©; 2024, ООО «Бионика Медиа»2024Bionika MediaООО «Бионика Медиа»https://journals.eco-vector.com/2073-4034/article/view/679982

The article discusses the features of thrombolytic therapy with alteplase in the treatment of ischemic stroke (IS) and acute coronary syndrome (ACS). Acute IS and ST-segment elevation myocardial infarction (STEMI) have a number of common features, but important differences in pathophysiology, diagnostics, and clinical features require an individual approach to each disease, with rapid treatment playing a decisive role in the prognosis of patients. According to the latest international and Russian guidelines and data from randomized clinical trials, approaches to various types of reperfusion therapy in IS and STEMI are analyzed. The objective of this review was to provide an understanding of the common and distinct pathophysiology underlying modern reperfusion strategies in IS and STEMI and to describe new ways to improve their clinical efficacy.

В статье обсуждаются особенности тромболитической терапии алтеплазой в лечении ишемического инсульта (ИИ) и острого коронарного синдрома (ОКС). Острый ИИ и инфаркт миокарда с подъемом сегмента ST (ИМПЅТ) имеют ряд общих черт, однако важные различия в патофизиологии, диагностике, клинических особенностях требуют индивидуального подхода к каждому заболеванию, при этом быстрое лечение играет определяющую роль для прогноза пациентов. Согласно последним международным и российским рекомендациям и данным рандомизированных клинических исследований, анализируются подходы к различным видам проведения реперфузионной терапии при ИИ и ИМПЅТ. Цель данного обзора – дать представление об общей и отличающейся друг от друга патофизиологии, лежащей в основе современных стратегий реперфузии при ИИ иИМПST, и описать новые способы повышения их клинической эффективности.

tissue plasminogen activator alteplaseischemic strokethrombectomyST-segment elevation myocardial infarctionthrombolytic therapyreperfusionpharmacoinvasive strategyтканевой активатор плазминогена алтеплазаишемический инсульттромбэктомияинфаркт миокарда с подъемом сегмента STтромболитическая терапияреперфузияфармакоинвазивная стратегияThygesen K., Alpert J.S., Jaffe A.S., et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J 2019;40:237–69. Doi: 10.1093/eurheartj/ehy462.Baaten C.C.F.M.J., Nagy M., Bergmeier W., et al. Platelet biology and function: plaque erosion vs. rupture. Eur Heart J 2024;45:18–31. Doi: 10.1093/eurheartj/ehad720.Saver J.L. Time is brain – quantified. Stroke 2006;37:263–6. Doi: 10.1161/01. STR.0000196957.55928.ab.2023 ESC Guidelines for the management of acute coronary syndromes: Developed by the task force on the management of acute coronary syndromes of the European Society of Cardiology (ESC). Eur Heart J. 2024;45(13):1145. Doi: 10.1093/eurheartj/ehad870.Turc G., Bhogal P., Fischer U., et al. European Stroke Organisation (ESO) – European Society for Minimally Invasive Neurological Therapy (ESMINT) guidelines on mechanical thrombectomy in acute ischemic stroke. J Neurointerv Surg. 2019;11:535–8. Doi: 10.1136/neurintsurg-2018-014568.Berge E., Whiteley W., Audebert H., et al. European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J. 2021;6:I–LXII. Doi: 10.1177/ 2396987321989865.Powers W.J., Rabinstein A.A., Ackerson T., et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50:e344–418. Doi: 10.1161/STR.0000000000000211.Клинические рекомендации. Ишемический инсульт и транзиторная ишемическая атака. Всероссийское общество неврологов. Ассоциация нейрохирургов России. МОО. «Объединение нейроанестезиологов и нейрореаниматологов». Союз реабилитологов России. М., 2024. 328 с. [Clinical guidelines. Ischemic stroke and transient ischemic attack. All-Russian Society of Neurologists. Association of Neurosurgeons of Russia. International Public Organization. «Association of Neuroanesthesiologists and Neuroresuscitators». Union of Rehabilitologists of Russia. Moscow, 2024. 328 p. (In Russ.)].The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischaemic stroke. N Engl J Med. 1995;333:1581–7.Hacke W., Kaste M., Fieschi C., et al. Intravenous thrombolysis withrecombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA. 1995;274:1017–25.Hacke W., Kaste M., Fieschi C., et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Lancet. 1998;352:1245–51.Wardlaw J.M., Sandercock P.A.G., Berge E. Thrombolytic therapy with recombinant tissue plasminogen activator for acute ischemic stroke. Where do we go from here? A cumulative meta-analysis. Stroke. 2003;34:1437–42.Wardlaw J.M., del Zoppo G., Yamaguchi T., Berge E. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev. 2003:D000213.The IST-3 collaborative group. The benefi ts and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet. 2012. published on-line May 23. Doi: 10.1016/S0140-6736(12)60768-5.Wardlaw J.M., Murray V., Berge E., del Zoppo G.J. Thrombolysis for acute ischaemic stroke. Cochrane Data-base Syst Rev. 2014:CD000213.Wardlaw J.M., Murray V., Berge E., et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet. 2012;379(9834):2364–72.Emberson J., Lees K.R., Lyden P., et al. Stroke Thrombolysis Trialists’ Collaborative Group. Effect of treatment delay, age, and stroke severity on the effects of intrave-nous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 201429;384(9958):1929–35. Doi: 10.1016/S0140-6736(14)60584-5.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;13(359):1317–29.Picanço M.R., Christensen S., Campbell B.C., et al. Reperfusion after 4.5 hours reduces infarct growth and improves clinical outcomes. Int J Stroke 2014;9(3):266–9.Campbell B.C.V., Ma H., Ringleb P.A., et al. EXTEND, ECASS-4, and EPITHET Investigators. Extending thrombolysis to 4·5-9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data. Lancet. 2019;394(10193):139–47.Anderson C.S., Robinson T., Lindley R.I., et al. ENCHANTED Investigators and Coordinators. Low-dose versus standard-dose intravenous alteplase in acute ischemic stroke. N Engl J Med. 2016;374:2313–23. Doi: 10.1056/NEJMoa1515510.Wang X., Robinson T.G., Lee T.H., et al. Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) Investigators. Low-Dose vs Standard-Dose Alteplase for Patients With Acute Ischemic Stroke: Secondary Analysis of the ENCHANTED Randomized Clinical Trial. JAMA. Neurol. 2017;74(11):1328–35.Carr S.J., Wang X., Olavarria V.V., et al. ENCHANTED Investigators. Influence of Renal Impairment on Outcome for Thrombolysis-Treated Acute Ischemic Stroke: ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) Post Hoc Analysis. Stroke. 2017;48(9):2605–9.Chen G., Wang X., Robinson T.G., et al. ENCHANTED Investigators. Comparative effects of low-dose versus standard-dose alteplase in ischemic patients with prior stroke and/or diabetes mellitus: The ENCHANTED trial. J Neurol Sci. 2018;387:1–5.Boersma E., Maas A.C.P., Deckers J.W., Simoons M.L., et al. Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour. Lancet. 1996;348:771–5.Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000patients. Lancet. 1994; 343:311–22.Widimsky P., Budesinsky T., Vorac D., et al. Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction: final results of the randomized national multicentre trial: PRAGUE-2. Eur Heart J. 2003;24:94–104.The European Myocardial Infarction Project Group. Prehospital thrombolytic therapy in patients with suspected acute myocardial infarction. N Engl J Med 1993;329:383–9.The TIMI Study Group. Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) Phase II trial. N Engl J Med. 1989;320:618–27.Gore J.M., Sloan M., Price T.R., et al, and the TIMI Investigators. Intracerebral hemorrhage, cerebral infarction, and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the thrombolysis in myocardial infarction study. Circulation. 1991;83:448–59.Topol E.J., Morriss D.C., Smalling R.W., et al. A multicenter, randomized, placebo-controlled trial of a new form of intravenous recombinant tissue-type plasminogen activator (Activase®) in acute myocardial infarction. J Am Coll Cardiol. 1997;9:1205–13.The GUSTO Investigators. An International Randomized Trial Comparing Four Thrombolytic Strategies for Acute Myocardial Infarction N. Engl. J. Med. 1993; 329: 673-682.Armstrong PW, Gershlick AH, Goldstein P, et al. Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction. N Engl J Med. 2013;368:1379–87. Doi: 10.1056/NEJMoa1301092.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;42:1775–7. Doi: 10. 1161/STROKEAHA.110.609693.Mueller L., Pult F., Meisterernst J., et al. Impact of intravenous thrombolysis on recanalization rates in patients with stroke treated with bridging therapy. Eur J Neurol. 2017;24:1016–21. Doi: 10.1111/ene.13330.Kaesmacher J., Cavalcante F., Kappelhof M., et al. Time to treatment with intravenous thrombolysis before thrombectomy and functional outcomes in acute ischemic stroke: a meta-analysis. JAMA. 2024;331:764–77. https://doi. org/10.1001/jama.2024.0589.LeCouffe N.E., Kappelhof M., Treurniet K.M., et al. A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke. N Engl J Med. 2021;385(20):1833–44. Doi: 10.1056/NEJMoa2107727.Suzuki K., Matsumaru Y., Takeuchi M., et al. Effect of Mechanical Thrombectomy Without vs With Intravenous Thrombolysis on Functional Outcome Among Patients With Acute Ischemic Stroke: The SKIP Randomized Clinical Trial. JAMA. 2021;325(3):244–53. Doi: 10.1001/jama.2020.23522. Erratum in: JAMA. 2021;325(17):1795.Zi W., Qiu Z., Li F., et al. Effect of Endovascular Treatment Alone vs Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Pa-tients With Acute Ischemic Stroke: The DEVT Randomized Clinical Trial. JAMA. 2021;325(3):234–43. Doi: 10.1001/jama.2020.23523.Maier I.L., Leha A., Badr M., et al. Inhouse Bridging Thrombolysis Is Associated With Improved Functional Outcome in Patients With Large Vessel Occlusion Stroke: Findings From the German Stroke Registry. Front Neurol. 2021;12:649108. Doi: 10.3389/fneur.2021.649108.Jian Y., Zhao L., Jia B., et al. ANGEL-ACT Study Group. Direct versus Bridging Mechanical Thrombectomy in Elderly Patients with Acute Large Vessel Occlusion: A Multicenter Cohort Study. Clin Interv Aging. 2021;16:1265–74. Doi: 10.2147/CIA.S313171.Goyal M., Menon B.K., van Zwam W.H, et al.; HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723–31. Doi: 10.1016/S0140-6736(16)00163-X.Bourcier R., Goyal M., Liebeskind D.S., et al.; HERMES Trialists Collaboration. Association of Time From Stroke Onset to Groin Puncture With Quality of Reperfusion After Mechanical Thrombectomy: A Meta-analysis of Individual Patient Data From 7 Randomized Clinical Trials. JAMA. Neurol. 201;76(4):405–11. Doi: 10.1001/jamaneurol.2018.4510.Jollis J.G., Granger C.B., Zegre-Hemsey J.K., et al. Treatment time and in-hospital mortality among patients with ST-segment elevation myocardial infarction, 2018–2021. JAMA. 2022;328:2033–40. Doi: 10.1001/ jama.2022.20149.Seners P., Turc G., Maier B., et al. Incidence and predictors of early recanalization after intravenous thrombolysis: a systematic review and meta-analysis. Stroke. 2016;47:2409–12. Doi: 10.1161/STROKEAHA.116. 014181.Kaesmacher J., Kleine J.F. Bridging therapy with i. v. rtPA in MCA occlusion prior to endovascular thrombectomy: a double-edged sword? Clin Neuroradiol. 2018;28:81–9. Doi: 10.1007/s00062-016-0533-0.Desilles J.P., Loyau S., Syvannarath V., et al. Alteplase reduces downstream microvascular thrombosis and improves the benefit of large artery recanalization in stroke. Stroke. 2015;46:3241–8. Doi: 10.1161/ STROKEAHA.115.010721.Fischer U., Kaesmacher J., Plattner P.S., et al. SWIFT DIRECT: Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA Versus DIRECT Solitaire Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke: methodology of a randomized, controlled, multicentre study. Int J Stroke. 2022;17:698–705. Doi: 10.1177/17474930211048768.Requena M., Ren Z., Ribo M. Direct transfer to angiosuite in acute stroke: why, when, and how? Neurology. 2021;97:S34–41. Doi: 10.1212/WNL.00000000000 12799.Palaiodimou L., Sarraj A., Safouris A., et al. Endovascular treatment for large-core ischaemic stroke: a meta-analysis of randomised controlled clinical trials. J Neurol Neurosurg Psych. 2023;94:781–5. Doi: 10.1136/jnnp-2023-331513.Scheldeman L., Wouters A, Lemmens R. Imaging selection for reperfusion therapy in acute ischemic stroke beyond the conventional time window. J Neurol. 2022;269:1715–23. Doi: 10.1007/s00415-021-10872-4.Broch K., Anstensrud A.K., Woxholt S., et al. Randomized trial of interleukin-6 receptor inhibition in patients with acute ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2021;77:1845–55. Doi: 10.1016/j.jacc.2021.02.049.Del Buono M.G., Damonte J.I., Moroni F., et al. Clinical and pharmacological implications of time to treatment with interleukin-1 blockade in ST-segment elevation myocardial infarction. J Pharmacol Exp Ther. 2023;386:156–63. Doi: 10.1124/jpet.123.001601.Hernandez-Jimenez M., Abad-Santos F., Cotgreave I., et al. Safety and efficacy of ApTOLL in patients with ischemic stroke undergoing endovascular treatment: a phase 1/2 randomized clinical trial. JAMA. Neurol. 2023;80:779–88. Doi: 10.1001/jamaneurol.2023.1660.Hill M.D., Goyal M., Menon B.K., et al. Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial. Lancet. 2020;395:878–87. Doi: 10.1016/S0140-6736(20)30258-0.