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Основные положения двойной антиагрегантной терапии и современные тенденции к ее изменению
Эрлих А.Д. Основные положения двойной антиагрегантной терапии и современные тенденции к ее изменению. Consilium Medicum. 2019; 21 (10): 79–84. DOI: 10.26442/20751753.2019.10.190547
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Erlih A.D. Main provisions of dual antiplatelet therapy and current trends in its change. Consilium Medicum. 2019; 21 (10): 79–84. DOI: 10.26442/20751753.2019.10.190547
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Аннотация
В настоящем материале представлен небольшой экскурс в историю двойной антиагрегантной терапии (ДАТ), основные положения современных подходов к ее использованию, а также на основании завершившихся рандомизированных клинических исследований сделано предположение о том, как могут измениться подходы к ДАТ в будущем. ДАТ в виде сочетания ацетилсалициловой кислоты (АСК) и одного из ингибиторов P2Y12-рецепторов (клопидогрел, прасугрел или тикагрелор) используется в клинической практике почти 20 лет, преимущественно рекомендованная к назначению в самую раннюю стадию острого коронарного синдрома (ОКС) или при плановом коронарном стентировании. Все годы существования ДАТ с ней связаны два основных вопроса: выбор препарата для ДАТ и длительность ДАТ. Если первый вопрос в настоящее время почти решен (в большинстве случаев ОКС в сочетании с АСК предпочтительны тикагрелор или прасугрел, а при плановом стентировании – клопидогрел), то проблемы длительности ДАТ продолжают обсуждаться. Современные положения о ДАТ можно описать словом «индивидуализация», что означает принятие отдельного решения о длительности ДАТ в зависимости от особенностей пациента и от соотношения у него выраженности геморрагического и ишемического рисков. Для облегчения решения о длительности ДАТ в настоящее время рекомендовано использование стандартизированных шкал PRECISE-DAPT и DAPT, значение которых позволяет сделать вывод о безопасной и эффективной длительности ДАТ. Данные завершившихся клинических исследований STOP-DAPT-2 и SMART-CHOICE позволяют предположить, что в скором будущем важным изменением ДАТ станет ее укорочение. В обоих этих исследованиях более короткая ДАТ превосходила ДАТ стандартной длительности по критериям безопасности и была сравнима с ней по эффективности. Еще одно важное изменение, как кажется, следует ждать в основных правилах антитромботического лечения после коронарного стентирования у пациентов с фибрилляцией предсердий. В этом случае необходимость сочетать ДАТ с оральным антикоагулянтом (ОАК) связана с худшим прогнозом из-за высокой вероятности кровотечений. Несколько относительно схожих по дизайну исследований – PIONEER-AF, RE-DUAL-PCI и особенно AU-GUSTUS – показали, что сочетание любого из не-витамин-К-ассоциированных ОАК с ингибитором P2Y12 (без АСК) уже с первых дней после коронарного стентирования может быть более безопасным и не менее эффективным вариантом лечения по сравнению с «тройной» терапией (ДАТ+ОАК).
Ключевые слова: двойная антиагрегантная терапия, ацетилсалициловая кислота, ингибитор P2Y12, острый коронарный синдром, коронарное стентирование, длительность, кровотечение.
Ключевые слова: двойная антиагрегантная терапия, ацетилсалициловая кислота, ингибитор P2Y12, острый коронарный синдром, коронарное стентирование, длительность, кровотечение.
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This article provides a small excursion into the history of dual antiplatelet therapy (DAT) as well as main points of modern approaches to its use. Based on completed randomized clinical trials it also makes an assumption about how approaches to DAT can change in the future. DAT as a combination of acetylsalicylic acid (ASA) and one of the P2Y12 receptor inhibitors (clopidogrel, prasugrel or ticagrelor) has been used in clinical practice for almost 20 years, its use is mainly recommended at the earliest stage of acute coronary syndrome (ACS) or at planned coronary stenting. Two main questions have always been related to DAT: the choice of drug for DAT and the duration of DAT. If the first question is now almost resolved (ticagrelor or prasugrel combined with ASA are preferred in most cases of ACS and clopidogrel combined with ASA is preferred for planned stenting), then the problems of DAT duration continue to be discussed. Current view on DAT can be described by the word "individualization", which means making a separate decision on the duration of DAT depending on the patient's characteristics and on the ratio of hemorrhagic and ischemic risks. To facilitate the decision on the duration of DAT the use of standardized PRECISE-DAPT and DAPT scales is currently recommended. Their values allow us to conclude what DAT duration is safe and effective. The data from the completed clinical studies STOP-DAPT-2 and SMART-CHOICE suggest that in the near future DAT duration will be shortened. In both of these studies, the shorter DAT was superior to the DAT of standard duration in terms of safety criteria and was comparable to it in terms of effectiveness. Another important change, as it seems, should be expected in the basic rules of antithrombotic treatment after coronary stenting in patients with atrial fibrillation. In this case, the need to combine DAT with oral anticoagulant (OAC) is associated with a worse prognosis due to the high probability of bleeding. Several studies with relatively similar design – PIONEER-AF, RE-DUAL-PCI, and especially AUGUSTUS – showed that from the first days after coronary stenting the combination of any of non-vitamin K antagonist OACs with a P2Y12 inhibitor (without ASA) may be safer and no less effective treatment option compared to the "triple" therapy (DAT + OAK).
Key words: double antiplatelet therapy, acetylsalicylic acid, P2Y12 inhibitor, acute coronary syndrome, coronary stenting, duration, bleeding.
Key words: double antiplatelet therapy, acetylsalicylic acid, P2Y12 inhibitor, acute coronary syndrome, coronary stenting, duration, bleeding.
Полный текст
Список литературы
1. The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes without ST-Segment Elevation. N Engl J Med 2001; 345: 494–502.
2. Wiviott SD, Braunwald E, McCabe CH et al.; for the TRITON–TIMI 38 Investigators. Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes. N Engl J Med 2007; 357: 2001–15.
3. Wallentin L, Becker RC, Budaj A et al.; PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361 (11): 1045–57.
4. Mauri L Kereiakes DJ, Yeh RW et al. for the DAPT Study Investigators. Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents. N Engl J Med 2014; 371: 2155–66.
5. Bonaca MP, Bhatt DL, Cohen M et al.; for the PEGASUS-TIMI-54 Steering Committee and Investigators. Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction. N Engl J Med 2015; 372: 1791–800.
6. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur Heart J 2018; 39: 213–54.
7. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 2019; 40: 87–165.
8. Costa F, van Klaveren D, James S et al.; PRECISE-DAPT Study Investigators. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet 2017; 389: 1025–34.
9. Yeh RW, Secemsky EA, Kereiakes DJ et al.; DAPT Study Investigators. Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention. JAMA 2016; 315 (16): 1735–49.
10. Urban P, Mehran R, Colleran R et al. Defining high bleeding risk in patients undergoing percutaneous coronary intervention. A consensus document from the academic research consortium for high bleeding risk. Circulation 2019; 140: 240–61.
11. Kikkert WJ, Damman P. Optimal duration of dual antiplatelet therapy for coronary artery disease. Neth Heart J 2018; 26 (8): 321–33.
12. Vranckx P, Valgimigli M, Juni P et al. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicenter, open-label, randomized superiority trial. Lancet 2018; 392 (10151): 940–9.
13. Watanabe H, Domei T, Morimoto T et al. Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCI. The STOPDAPT-2 Randomized Clinical Trial. JAMA 2019; 321 (24): 2414–27.
14. Hahn JY, Song YB, Oh J-H et al. Effect of P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy on Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention. The SMART-CHOICE Randomized Clinical Trial. JAMA 2019; 321 (24): 2428–37.
15. Dewilde WJ, Oirbans T, Verheugt FW et al.; WOEST study investigators. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 2013; 381 (9872): 1107–15.
16. Gibson CM, Mehran R, Bode C et al. Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med 2016; 375: 2423–34.
17. Cannon CP, Bhatt DL, Oldgren J et al.; for the RE-DUAL PCI Steering Committee and Investigators. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med 2017; 377: 1513–24.
18. Lopes RD, Heizer G, Aronson R et al.; for the AUGUSTUS Investigators. Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. N Engl J Med 2019; 380: 1509–24.
2. Wiviott SD, Braunwald E, McCabe CH et al.; for the TRITON–TIMI 38 Investigators. Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes. N Engl J Med 2007; 357: 2001–15.
3. Wallentin L, Becker RC, Budaj A et al.; PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361 (11): 1045–57.
4. Mauri L Kereiakes DJ, Yeh RW et al. for the DAPT Study Investigators. Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents. N Engl J Med 2014; 371: 2155–66.
5. Bonaca MP, Bhatt DL, Cohen M et al.; for the PEGASUS-TIMI-54 Steering Committee and Investigators. Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction. N Engl J Med 2015; 372: 1791–800.
6. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur Heart J 2018; 39: 213–54.
7. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 2019; 40: 87–165.
8. Costa F, van Klaveren D, James S et al.; PRECISE-DAPT Study Investigators. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet 2017; 389: 1025–34.
9. Yeh RW, Secemsky EA, Kereiakes DJ et al.; DAPT Study Investigators. Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention. JAMA 2016; 315 (16): 1735–49.
10. Urban P, Mehran R, Colleran R et al. Defining high bleeding risk in patients undergoing percutaneous coronary intervention. A consensus document from the academic research consortium for high bleeding risk. Circulation 2019; 140: 240–61.
11. Kikkert WJ, Damman P. Optimal duration of dual antiplatelet therapy for coronary artery disease. Neth Heart J 2018; 26 (8): 321–33.
12. Vranckx P, Valgimigli M, Juni P et al. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicenter, open-label, randomized superiority trial. Lancet 2018; 392 (10151): 940–9.
13. Watanabe H, Domei T, Morimoto T et al. Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCI. The STOPDAPT-2 Randomized Clinical Trial. JAMA 2019; 321 (24): 2414–27.
14. Hahn JY, Song YB, Oh J-H et al. Effect of P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy on Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention. The SMART-CHOICE Randomized Clinical Trial. JAMA 2019; 321 (24): 2428–37.
15. Dewilde WJ, Oirbans T, Verheugt FW et al.; WOEST study investigators. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 2013; 381 (9872): 1107–15.
16. Gibson CM, Mehran R, Bode C et al. Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med 2016; 375: 2423–34.
17. Cannon CP, Bhatt DL, Oldgren J et al.; for the RE-DUAL PCI Steering Committee and Investigators. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med 2017; 377: 1513–24.
18. Lopes RD, Heizer G, Aronson R et al.; for the AUGUSTUS Investigators. Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. N Engl J Med 2019; 380: 1509–24.
________________________________________________
1. The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes without ST-Segment Elevation. N Engl J Med 2001; 345: 494–502.
2. Wiviott SD, Braunwald E, McCabe CH et al.; for the TRITON–TIMI 38 Investigators. Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes. N Engl J Med 2007; 357: 2001–15.
3. Wallentin L, Becker RC, Budaj A et al.; PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361 (11): 1045–57.
4. Mauri L Kereiakes DJ, Yeh RW et al. for the DAPT Study Investigators. Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents. N Engl J Med 2014; 371: 2155–66.
5. Bonaca MP, Bhatt DL, Cohen M et al.; for the PEGASUS-TIMI-54 Steering Committee and Investigators. Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction. N Engl J Med 2015; 372: 1791–800.
6. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur Heart J 2018; 39: 213–54.
7. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 2019; 40: 87–165.
8. Costa F, van Klaveren D, James S et al.; PRECISE-DAPT Study Investigators. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet 2017; 389: 1025–34.
9. Yeh RW, Secemsky EA, Kereiakes DJ et al.; DAPT Study Investigators. Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention. JAMA 2016; 315 (16): 1735–49.
10. Urban P, Mehran R, Colleran R et al. Defining high bleeding risk in patients undergoing percutaneous coronary intervention. A consensus document from the academic research consortium for high bleeding risk. Circulation 2019; 140: 240–61.
11. Kikkert WJ, Damman P. Optimal duration of dual antiplatelet therapy for coronary artery disease. Neth Heart J 2018; 26 (8): 321–33.
12. Vranckx P, Valgimigli M, Juni P et al. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicenter, open-label, randomized superiority trial. Lancet 2018; 392 (10151): 940–9.
13. Watanabe H, Domei T, Morimoto T et al. Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCI. The STOPDAPT-2 Randomized Clinical Trial. JAMA 2019; 321 (24): 2414–27.
14. Hahn JY, Song YB, Oh J-H et al. Effect of P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy on Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention. The SMART-CHOICE Randomized Clinical Trial. JAMA 2019; 321 (24): 2428–37.
15. Dewilde WJ, Oirbans T, Verheugt FW et al.; WOEST study investigators. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 2013; 381 (9872): 1107–15.
16. Gibson CM, Mehran R, Bode C et al. Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med 2016; 375: 2423–34.
17. Cannon CP, Bhatt DL, Oldgren J et al.; for the RE-DUAL PCI Steering Committee and Investigators. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med 2017; 377: 1513–24.
18. Lopes RD, Heizer G, Aronson R et al.; for the AUGUSTUS Investigators. Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. N Engl J Med 2019; 380: 1509–24.
Авторы
А.Д. Эрлих
ГБУЗ «Городская клиническая больница №29 им. Н.Э. Баумана» Департамента здравоохранения г. Москвы, Москва, Россия
alexeyerlikh@gmail.com
ГБУЗ «Городская клиническая больница №29 им. Н.Э. Баумана» Департамента здравоохранения г. Москвы, Москва, Россия
alexeyerlikh@gmail.com
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Aleksei D. Erlih
Bauman City Clinical Hospital №29, Moscow, Russia
alexeyerlikh@gmail.com
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