smpСкорая медицинская помощьEMERGENCY MEDICAL CARE2072-6716Northwest State Medical University named after II Mechnikov10.24884/2072-6716-2021-22-4-4-11smp-515Research ArticleСТАТЬИARTICLESАнтитромботическая терапия при остром коронарном синдроме: новые клинические рекомендации, спорные вопросы и роль догоспитального этапаAntithrombotic therapy in acute coronary syndromes setting: new clinical guidelines, controversial issues and the role of prehospital stageШальневВ. И.ShalnevV. I.

Шальнев Владимир Ильич — доктор медицинских наук, профессор кафедры скорой медицинской помощи

191015, Санкт-Петербург, Кирочная ул., д. 41

Vladimir I. Shalnev

St. Petersburg

VISSZGMU@yandex.ruПетроваН. В.PetrovaN. V.

Петрова Нелли Владимировна — кандидат медицинских наук, доцент кафедры скорой медицинской помощи

191015, Санкт-Петербург, Кирочная ул., д. 41

Nelly V. Petrova

St. Petersburg

ЛукьяноваИ. Ю.LukianovaI. Yu.

Лукьянова Ирина Юрьевна — доктор медицинских наук, доцент кафедры скорой медицинской помощи; доцент кафедры факультетской терапии

191015, Санкт-Петербург, Кирочная ул., д. 41

199034, Санкт-Петербург, Университетская наб., д. 7–9

тел.: 8 (812) 303–50–00

Irina Yu. Lukianova

St. Petersburg

rectorat@szgmu.ruСеверо-Западный государственный медицинский университет им. И. И. МечниковаРоссияNorth-Western State Medical University named after I. I. MechnikovRussian FederationСеверо-Западный государственный медицинский университет им. И. И. Мечникова; Санкт-Петербургский государственный университетРоссияNorth-Western State Medical University named after I. I. Mechnikov; St. Petersburg State UniversityRussian Federation202119012022224411Copyright © Шальнев В.И., Петрова Н.В., Лукьянова И.Ю., 20222022Шальнев В.И., Петрова Н.В., Лукьянова И.Ю.Shalnev V.I., Petrova N.V., Lukianova I.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://smp.spb.ru/jour/article/view/515

Антитромботическая терапия (АТТ) является одним из основных компонентов в терапии острого коронарного синдрома (ОКС), предотвращая развитие тромбоза в коронарной артерии или ограничивая его прогрессирование. Этот вид терапии традиционно назначался в максимально ранние сроки от развития ОКС, обычно на догоспитальном этапе (ДГЭ). Однако доказательств, подтверждающих преимущество начала АТТ на догоспитальном этапе по сравнению с назначением в стационаре, на сегодня не существует. Проведенные в последние несколько лет клинические исследования и анализ регистров по лечению ОКС показали, что назначение одного из основных компонентов данной терапии, ингибиторов тромбоцитарных рецепторов Р2Y12 (клопидогрел, тикагрелол, праcугрел), в нагрузочных дозах на догоспитальном этапе не улучшает течение заболевания и приводит к большей частоте кровотечений по сравнению с назначением в стационаре. Последние версии рекомендаций Европейского и Российского кардиологических обществ по лечению ОКС 2020 года не рекомендуют назначение ингибиторов Р2Y12 рецепторов на догоспитальном этапе. В статье рассматривается современная тактика АТТ при ОКС, обсуждаются возможные варианты адаптации указанных рекомендаций к сложившейся практике применения антитромботических средств при ОКС.

Antithrombotic therapy is a cornerstone of acute coronary syndromes treatment, preventing coronary artery thrombosis development and progression. Early administration of P2Y12 receptor antagonists to patients with acute coronary syndromes (ACS) at the prehospital stage is a common practice and has been supported by the European and Russian Societies of Cardiology guidelines for many years despite the lack of definite evidence for its benefit. Recent clinical trials and registers on ACS treatment have shown no benefit and higher prevalence of bleeding related to the early start of P2Y12 receptor antagonists in NSTE-ACS patients. The latest European and Russian Societies of Cardiology guidelines do not recommend prehospital administration of P2Y12 receptor antagonists. The article highlights the antithrombotic therapy in acute coronary syndromes setting, recent ESC guidelines and its possible implementation in common practice.

острый коронарный синдромантитромботическая терапияантагонисты тромбоцитарных рецепторов Р2Y12acute coronary syndromesantithrombotic therapyP2Y12 receptor antagonistsReferencesОстрый инфаркт миокарда с подъемом сегмента ST электрокардиограммы. Российские клинические рекомендации 2020. Доступно на сайте Российского кардиологического общества: www.scardio.ruAcute myocardial infarction with ST segment elevation on ECG. Clinical guidelines. Russian Society of Cardiology. 2020. Available on the website RKO, https: scardio.ru (In Russ.)Острый коронарный синдром без подъема сегмента ST электрокардиограммы. Российские клинические рекомендации 2020. Доступно на сайте Российского кардиологического общества: www.scardio.ruAcute coronary syndrome in patients presenting without persistent ST‑segment elevation. Clinical guidelines. Russian Society of Cardiology, 2020. Available on the website RKO, https: scardio.ru (In Russ.)Ibanez B., Agawall S., Antunes M. et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST‑segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST‑segment elevation of the European Society of Cardiology // Eur. Heart J. 2018. Vol. 39. P. 119–177. doi: 10.1093/eurheart/ehj393.Ibanez B., Agawall S., Antunes M. et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST‑segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST‑segment elevation of the European Society of Cardiology // Eur. Heart J. 2018. Vol. 39. P. 119–177. doi: 10.1093/eurheart/ehj393.Collet J-P., Thiele H., Barbato E. et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST‑segment elevation: The Task Force for the management of acute coronary syndromes in patients presenting without persistent ST‑segment elevation of the European Society of Cardiology (ESC) // Eur. Heart J. 2021. Vol. 42. P. 1289–1367. https://doi.org/10.1093/eurheartj/ehaa575.Collet J-P., Thiele H., Barbato E. et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST‑segment elevation: The Task Force for the management of acute coronary syndromes in patients presenting without persistent ST‑segment elevation of the European Society of Cardiology (ESC) // Eur. Heart J. 2021. Vol. 42. P. 1289–1367. https://doi.org/10.1093/eurheartj/ehaa575.Valgimigli M., Bueno H., Byrne R. et al. 2017 ESC Focused Update on Dual Antiplatelet Therapy in Coronary Artery Disease in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). The Task Force for the Management of Dual Antiplatelet Therapy in Coronary Artery Disease of the European Society of Cardiology // Eur. Heart J. 2018. Vol. 39. P. 213–260. doi: 10.1093/eurheart/ehj419.Valgimigli M., Bueno H., Byrne R. et al. 2017 ESC Focused Update on Dual Antiplatelet Therapy in Coronary Artery Disease in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). The Task Force for the Management of Dual Antiplatelet Therapy in Coronary Artery Disease of the European Society of Cardiology // Eur. Heart J. 2018. Vol. 39. P. 213–260. doi: 10.1093/eurheart/ehj419.Layne K., Ferro A. Antiplatelet Therapy in Acute Coronary Syndrome // Eur. Cardiol. 2017. Vol. 12 (1). P. 33–37. doi: 10.15420/ecr.2016:34:2.Layne K., Ferro A. Antiplatelet Therapy in Acute Coronary Syndrome // Eur. Cardiol. 2017. Vol. 12 (1). P. 33–37. doi: 10.15420/ecr.2016:34:2.Duggan S.T., Keating G. M. Prasugrel: a rewiew of its use in patients with acute coronary syndromes // Drugs. 2009. Vol. 69 (12). P. 1707–1726. doi: 10.2165/10484.190.000000000–00000.Duggan S.T., Keating G. M. Prasugrel: a rewiew of its use in patients with acute coronary syndromes // Drugs. 2009. Vol. 69 (12). P. 1707–1726. doi: 10.2165/10484.190.000000000–00000.Patti G., Colonna G., Pasceri V. et al. Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: Results from the ARMYDA‑2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study // Circulation. 2005. Vol. 111. P. 2099–2106.Patti G., Colonna G., Pasceri V. et al. Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: Results from the ARMYDA‑2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study // Circulation. 2005. Vol. 111. P. 2099–2106.Cuisset T., Frere C., Quilici J. et al. Benefit of a 600 mg loading dose of clopidogrel on platelet reactivity and clinical outcomes in patients with non-ST‑segment elevation acute coronary syndrome undergoing coronary stenting // J. Am. Coll. Cardiol. 2006. Vol. 48. P. 1339–1345.Cuisset T., Frere C., Quilici J. et al. Benefit of a 600 mg loading dose of clopidogrel on platelet reactivity and clinical outcomes in patients with non-ST‑segment elevation acute coronary syndrome undergoing coronary stenting // J. Am. Coll. Cardiol. 2006. Vol. 48. P. 1339–1345.von Beckerath N., Taubert D., Pogatsa-Murray G. et al. Absorption, metabolization, and antiplatelet effects of 300-, 600-, and 900-mg loading doses of clopidogrel: Results of the ISAR-CHOICE (Intracoronary stenting and Antithrombotic Regimen: Choose Between 3 High Oral Doses for Immediate Clopidogrel Effect) trial // Circulation. 2005. Vol. 112. P. 2946–2950.von Beckerath N., Taubert D., Pogatsa-Murray G. et al. Absorption, metabolization, and antiplatelet effects of 300-, 600-, and 900-mg loading doses of clopidogrel: Results of the ISAR-CHOICE (Intracoronary stenting and Antithrombotic Regimen: Choose Between 3 High Oral Doses for Immediate Clopidogrel Effect) trial // Circulation. 2005. Vol. 112. P. 2946–2950.James S.K., Roe M. T., Cannon C. P. et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management: substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial // Brit. Med. J. 2011. Vol. 342. P. d3527.James S.K., Roe M. T., Cannon C. P. et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management: substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial // Brit. Med. J. 2011. Vol. 342. P. d3527.Wiviott S.D., Braunwald E., McCabe C.H. et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes // New Engl. J. Med. 2007. Vol. 357. P. 2001–2015.Wiviott S.D., Braunwald E., McCabe C.H. et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes // New Engl. J. Med. 2007. Vol. 357. P. 2001–2015.Wallentin L., Becker R. C., Budaj A. et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes // New Engl. J. Med. 2009. Vol. 361. P. 1045–1057.Wallentin L., Becker R. C., Budaj A. et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes // New Engl. J. Med. 2009. Vol. 361. P. 1045–1057.Mega J.L., Braunwald E., Wiviott D. et al. Rivaroxaban in Patients with a Recent Acute Coronary Syndrome // New Engl. J. Med. 2012. Vol. 366. P. 9–19. doi: 0.1056/NEJMoa1112277.Mega J.L., Braunwald E., Wiviott D. et al. Rivaroxaban in Patients with a Recent Acute Coronary Syndrome // New Engl. J. Med. 2012. Vol. 366. P. 9–19. doi: 0.1056/NEJMoa1112277.Шальнев В. И. Современная тактика лечения и профилактики венозных тромбозов и тромбоэмболий. Роль новых пероральных антикоагулянтов (Часть I) // Скорая медицинская помощь. 2017. № 2. С. 37–44.Shalnev V.I. А Modern Approach to the treatment and prophilaxis of venous tromboembolism. The role of new oral anticoagulants. Part I. Emergency Medical Care, 2017, No. 2, pp. 37–44 (In Russ.). https://doi.org/10.24884/2072–6716–2017–18–2–37–44.Шальнев В. И. Современная тактика лечения и профилактики венозных тромбозов и тромбоэмболий. Роль новых пероральных антикоагулянтов (Часть II) // Скорая медицинская помощь. 2017. № 4. С. 60–65.Shalnev V.I. А Modern Approach to the treatment and prophilaxis of venous tromboembolism. The role of new oral anticoagulants. Part II. Emergency Medical Care, 2017, No. 4, pp. 60–65 (In Russ.) https://doi.org/10.24884/2072–6716–2017–18–4–60–65.Montalescot G., Bolognese L., Dudek D. et al. ACCOAST Investigators. Pretreatment with prasugrel in non-ST segment elevation acute coronary syndromes // New Engl. J. Med. 2013. Vol. 369 (11). P. 999–1010. doi: 10.1056/NEJMoa1308075.Montalescot G., Bolognese L., Dudek D. et al. ACCOAST Investigators. Pretreatment with prasugrel in non-ST segment elevation acute coronary syndromes // New Engl. J. Med. 2013. Vol. 369 (11). P. 999–1010. doi: 10.1056/NEJMoa1308075.Schupke S., Neumann F.-J., Menichelli M. et al. ISAR-REACT 5 Trial Investigators. Ticagrelor or prasugrel in patients with acute coronary syndromes // New Engl. J. Med. 2019. Vol. 381 (16). P. 1524–1534. doi: 10.1056/NEJMoa1908973Schupke S., Neumann F.-J., Menichelli M. et al. ISAR-REACT 5 Trial Investigators. Ticagrelor or prasugrel in patients with acute coronary syndromes // New Engl. J. Med. 2019. Vol. 381 (16). P. 1524–1534. doi: 10.1056/NEJMoa1908973Sahlen A., Varenhorst C., Lagerqvist B. et al. Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registry // Eur. Heart J. 2016. Vol. 37 (44). P. 3335–3342. doi: 10.1093/eurheartj/ehw284.Sahlen A., Varenhorst C., Lagerqvist B. et al. Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registry // Eur. Heart J. 2016. Vol. 37 (44). P. 3335–3342. doi: 10.1093/eurheartj/ehw284.Mehta S.R., Yusuf S., Peters R. J. et al. Clopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI–CURE study // Lancet. 2001. Vol. 358. P. 527–533. doi: 10. 1016/S0140–6736(01)05701–4.Mehta S.R., Yusuf S., Peters R. J. et al. Clopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI–CURE study // Lancet. 2001. Vol. 358. P. 527–533. doi: 10. 1016/S0140–6736(01)05701–4.Steinhubl S.R., Berger P. B., Mann J.T III et al. CREDO Investigators; Clopidogrel for the Reduction of Events During Observation. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial // JAMA. 2002. Vol. 288 (19). P. 2411–2420. doi: 10.1001/jama.288.19.2411.Steinhubl S.R., Berger P. B., Mann J.T III et al. CREDO Investigators; Clopidogrel for the Reduction of Events During Observation. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial // JAMA. 2002. Vol. 288 (19). P. 2411–2420. doi: 10.1001/jama.288.19.2411.Sabatine M.S., Cannon C. P., Gibson C. M. et al. Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY) — Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators. Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST‑elevation myocardial infarction treated with fibrinolytics: the PCI–CLARITY study // JAMA. 2005. Vol. 294 (10). P. 1224–1232. doi: 10.1001/jama.294.10.1224.Sabatine M.S., Cannon C. P., Gibson C. M. et al. Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY) — Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators. Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST‑elevation myocardial infarction treated with fibrinolytics: the PCI–CLARITY study // JAMA. 2005. Vol. 294 (10). P. 1224–1232. doi: 10.1001/jama.294.10.1224.Bellemain-Appaix A., Kerneis M., O’Connor S.A. et al. ACTION study Group. Reappraisal of thienopyridine pretreatment in patients with non-ST elevation acute coronary syndrome: a systematic review and meta-analysis // Brit. Med. J. 2014. Vol. 349. P. g6269. doi: 10.1136/bmj.g6269.Bellemain-Appaix A., Kerneis M., O’Connor S.A. et al. ACTION study Group. Reappraisal of thienopyridine pretreatment in patients with non-ST elevation acute coronary syndrome: a systematic review and meta-analysis // Brit. Med. J. 2014. Vol. 349. P. g6269. doi: 10.1136/bmj.g6269.Bellemain-Appaix A., Begue C., Bhatt D. L. et al. The efficacy of early versus delayed P2Y12 inhibition in percutaneous coronary intervention for ST‑elevation myocardial infarction: a systematic review and metaanalysis. // Euro Intervention. 2018. Vol. 14 (1). P. 78–85. doi: 10.4244/EIJ-D‑17–00852.Bellemain-Appaix A., Begue C., Bhatt D. L. et al. The efficacy of early versus delayed P2Y12 inhibition in percutaneous coronary intervention for ST‑elevation myocardial infarction: a systematic review and metaanalysis. // Euro Intervention. 2018. Vol. 14 (1). P. 78–85. doi: 10.4244/EIJ-D‑17–00852.Stone G.W., McLaurin B.T., Cox D. A. et al. ACUITY Investigators. Bivalirudin for patients with acute coronary syndromes // New Engl. J. Med. 2006. Vol. 355 (21). P. 2203–2216. doi: 10.1056/NEJMoa062437.Stone G.W., McLaurin B.T., Cox D. A. et al. ACUITY Investigators. Bivalirudin for patients with acute coronary syndromes // New Engl. J. Med. 2006. Vol. 355 (21). P. 2203–2216. doi: 10.1056/NEJMoa062437.Roe M.T., Armstrong P. W., Fox K. A. et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization // New Engl. J. Med. 2012. Vol. 367. P. 1297–1309.Roe M.T., Armstrong P. W., Fox K. A. et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization // New Engl. J. Med. 2012. Vol. 367. P. 1297–1309.

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