Антагонисты минералокортикоидных рецепторов в лечении пациентов с постинфарктной сердечной недостаточностью: роль эплеренона
Антагонисты минералокортикоидных рецепторов в лечении пациентов с постинфарктной сердечной недостаточностью: роль эплеренона
Кашталап В.В., Седых Д.Ю., Барбараш О.Л. Антагонисты минералокортикоидных рецепторов в лечении пациентов с постинфарктной сердечной недостаточностью: роль эплеренона. Consilium Medicum. 2019; 21 (1): 51–55. DOI: 10.26442/20751753.2019.1.190260
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Kashtalap V.V., Sedykh D.Yu., Barbarash O.L. Antagonists of mineralocorticoid receptors in the treatment of patients with post-infarced heart failure: the role of eplerenone. Consilium Medicum. 2019; 21 (1): 51–55. DOI: 10.26442/20751753.2019.1.190260
Антагонисты минералокортикоидных рецепторов в лечении пациентов с постинфарктной сердечной недостаточностью: роль эплеренона
Кашталап В.В., Седых Д.Ю., Барбараш О.Л. Антагонисты минералокортикоидных рецепторов в лечении пациентов с постинфарктной сердечной недостаточностью: роль эплеренона. Consilium Medicum. 2019; 21 (1): 51–55. DOI: 10.26442/20751753.2019.1.190260
________________________________________________
Kashtalap V.V., Sedykh D.Yu., Barbarash O.L. Antagonists of mineralocorticoid receptors in the treatment of patients with post-infarced heart failure: the role of eplerenone. Consilium Medicum. 2019; 21 (1): 51–55. DOI: 10.26442/20751753.2019.1.190260
Цель. Осветить современные представления о роли антагонистов минералокортикоидных рецепторов (АМКР), в частности эплеренона, в лечении пациентов с постинфарктной сердечной недостаточностью, а также проанализировать их эффективность и безопасность. Материалы и методы. Рассмотрены данные научных источников, опубликованных в российской и зарубежной печати в 1984–2018 гг. Заключение. Перенесенный острый инфаркт миокарда с развитием клиники хронической сердечной недостаточности (ХСН) ассоциируется с гиперактивацией симпатоадреналовой системы и ренин-ангиотензин-альдостеронового каскада, что в конечном итоге приводит к формированию феномена патологического ремоделирования миокарда левого желудочка вследствие фиброза. В рамках концепции улучшения качества жизни и увеличения продолжительности жизни пациентов после инфаркта миокарда важным представляется назначение, помимо ингибиторов ренин-ангиотензин-альдостероновой системы и b-адреноблокаторов (b-АБ), АМКР, в частности, эплеренона. Накопленная информация об эффективности АМКР у пациентов с ХСН, в том числе и после перенесенного инфаркта миокарда, стала основой для включения препаратов в Национальные рекомендации по острой сердечной недостаточности Российского кардиологического общества и Российского научного медицинского общества терапевтов по диагностике и лечению ХСН. Согласно указанному документу препараты этой группы показаны (класс IA) к применению (в сочетании с ингибиторами ангиотензинпревращающего фермента – ИАПФ и b-АБ) у всех больных с умеренной и тяжелой ХСН со сниженной сократительной функцией левого желудочка для снижения риска смерти, частоты повторных госпитализаций и улучшения симптоматики. Аналогичная точка зрения отражена в рекомендациях Европейского общества кардиологов, в которых АМКР также присвоен класс доказательности IA как препарата 1-й линии (наряду с ИАПФ и b-АБ для лечения ХСН). Представленный клинический случай с опорой на доказательную базу ранее проведенных рандомизированных исследований демонстрирует ведущую роль эплеренона в улучшающей прогноз терапии у постинфарктных пациентов с ХСН и низкой фракцией выброса левого желудочка.
Aim. To present modern view on the role of mineralocorticoid receptor antagonists (MRA), eplerenone in particular, in treatment of patients with post-infarction cardiac failure, and to analyze its effectiveness and safety. Materials and methods. Data fr om scientific sources published in Russia and abroad in 1984–2018 years were analyzed. Conclusion. Acute myocardial infarction with congestive cardiac failure (CCF) development is associated with sympathoadrenal system and renin-angiotensin-aldosterone cascade hyperactivation that results in pathologic myocardium remodeling following fibrosis. Within the concept of quality of life improvement and lifetime increase in patients after myocardial infarction it is important to prescribe MRA, eplerenone in particular, besides renin-angiotensin-aldosterone system inhibitors and b-adrenoblockers (b-AB). Accumulated data on MRA effectiveness in patients with CCF including patients after myocardial infarction is the basis for inclusion of these medications in National guidelines on CSF diagnostics and treatment of Russian Society of Cardiology and Russian Scientific Medical Society of Therapists. According to these guidelines medications of this group are recommended (level IA) to the use (combined with angiotensin-converting enzyme inhibitors – ACE inhibitors and b-AB) in all patients with medium severe and severe CHF who have decreased contractile function of left ventricle in order to decrease mortality risk and readmission frequency and to improve symptoms. A similar point of view is presented in European Society of Cardiology guidelines wh ere MRA also have IA level of evidence to the use as a first line medication (together with ACE inhibitors and b-AB for CHF treatment). The presented clinical case supported by the evidence of previously conducted studies demonstrates the leading role of eplerenon in therapy that results in prognosis improvement in patients with CHF after myocardial infarction who have low left ventricular ejection fraction.
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[Sumin A.N. Optimal'naia medikamentoznaia terapiia khronicheskoi serdechnoi nedostatochnosti: rol' antagonistov mineralokortikoidnykh retseptorov. RMZh. 2018; 11 (1): 71–5 (in Russian).]
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[Zykov M.V., Zykova D.S., Kashtlap V.V. et al. Znachimost' mul'tifokal'nogo ateroskleroza dlia modifikatsii shkaly riska otdalennoi smertnosti GRACE u bol'nykh ostrym koronarnym sindromom s pod"emom segmenta ST. Ateroskleroz. 2012; 8 (1): 14–20 (in Russian).]
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[Kosiagina D.D., Zavyrylina P.N., Sedykh D.Iu. et al. Faktory, assotsiirovannye s pozdnim obrashcheniem za meditsinskoi pomoshch'iu pri infarkte miokarda. Kompleksnye problemy serdechno-sosudistykh zabolevanii. 2017; 3: 104–12 (in Russian).]
4. Komajda M, Cowie MR, Tavazzi L et al. QUALIFY Investigators. Physicians’ guideline adherence is associated with better prognosis in outpatients with heart failure with reduced ejection fraction: the QUALIFY international registry. Eur J Heart Fail 2017; 19 (11): 1414–23. DOI: 10.1002/ejhf.887
5. Гиляревский С.Р., Голшмид М.В., Кузьмина И.М. Роль антагонистов рецепторов альдостерона в профилактике и лечении сердечно-сосудистых и почечных заболеваний: реальность и перспективы. Рус. мед. журн. 2014; 23: 1689–98.
[Giliarevskii S.R., Golshmid M.V., Kuz'mina I.M. Rol' antagonistov retseptorov al'dosterona v profilaktike i lechenii serdechno-sosudistykh i pochechnykh zabolevanii: real'nost' i perspektivy. Rus. med. zhurn. 2014; 23: 1689–98 (in Russian).]
6. Nagarajan V, Chamsi-Pasha M, Tang WH. The role of aldosterone receptor antagonists in the management of heart failure: an update. Cleve Clin J Med 2012; 79: 631–39.
7. Edelmann F, Schmidt AG, Gelbrich G et al. Rationale and design of the “aldosterone receptor blockade in diastolic heart failure” trial: a double-blind, randomized, placebo-controlled, parallel group study to determine the effects of spironolactone on exercise capacity and diastolic function in patients with symptomatic diastolic heart failure (Aldo-DHF). Eur J Heart Fail 2010; 12: 874–82.
8. MacFadyen RJ, Lee AF, Morton JJ et al. How often are angiotensin II and aldosterone concentrations raised during chronic ACE inhibitor treatment in cardiac failure? Heart 1999; 82: 57–61.
9. Национальные рекомендации ОССН, РКО и РНМОТ. Сердечная недостаточность: хроническая и острая декомпенсированная. Диагностика, профилактика и лечение (5-й пересмотр). М., 2018. DOI: 10.18087/cardio. 2475
[Natsional'nye rekomendatsii OSSN, RKO i RNMOT. Serdechnaia nedostatochnost': khronicheskaia i ostraia dekompensirovannaia. Diagnostika, profilaktika i lechenie (5-i peresmotr). Moscow, 2018. DOI: 10.18087/cardio. 2475 (in Russian).]
10. McKelvie RS, Yusuf S, Pericak D et al. Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation 1999; 100: 1056–64.
11. Vizzardi E, Nodari S, Caretta G et al. Effects of spironolactone on long-term mortality and morbidity in patients with heart failure and mild or no symptoms. Am J Med Sci 2014; 347 (4): 271–6.
12. Pitt B, Zannad F, Remme WJ et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999; 341: 709–17.
13. Jeunemaitre X, Chatellier G., Kreft-Jais C et al. Efficacy and tolerance of spironolactone in essential hypertension. Am J Cardiol 1987; 60: 820–5.
14. Sabbadin C, Calò LA, Armanini D. The story of spironolactones from 1957 to now: from sodium balance to inflammation. G Ital Nefrol 2016; 33 (Suppl. 66): 33.
15. De Gasparo M, Joss U, Ramjoué HP et al. Three new epoxy-spirolactone derivatives: characterization in vivo and in vitro. J Pharmacol Exp Ther 1987; 240: 650–6.
16. Pitt B, Remme W, Zannad F et al. Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348: 1309–21.
17. Pitt B, White H, Nicolau J et al., EPHESUS Investigators. Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure. J Am Coll Cardiol 2005; 46: 425–31.
18. Подзолков В.И., Драгомирецкая Н.А. Антагонисты альдостерона. Современные представления о механизмах действия и эффектах спиронолактона. Рацион. фармакотерапия в кардиологии. 2017; 13 (2): 263–9. DOI: http://dx.doi.org/10.20996/1819-6446-2017-13-2-263-269 [Podzolkov V.I., Dragomiretskaia N.A. Antagonisty al'dosterona. Sovremennye predstavleniia o mekhanizmakh deistviia i effektakh spironolaktona. Ratsion. farmakoterapiia v kardiologii. 2017; 13 (2): 263–9. DOI: http://dx.doi.org/10.20996/1819-6446-2017-13-2-263-269 (in Russian).]
19. Iqbal J, Fay R, Adlam D et al. Effect of eplerenone in percutaneous coronary intervention-treated post-myocardial infarction patients with left ventricular systolic dysfunction: a subanalysis of the EPHESUS trial. Eur J Heart Fail 2014; 16: 685–91.
20. Carillo S, Zhang Y, Fay R et al. Heart failure with systolic dysfunction complicating acute myocardial infarction – differential outcomes but similar eplerenone efficacy by ST-segment or non-ST-segment elevation: a post hoc substudy of the EPHESUS trial. Arch Cardiovasc Dis 2014; 107: 149–57.
21. Tsutamoto T, Wada A, Maeda K et al. Spironolactone inhibits the transcardiac extraction of aldosterone in patients with congestive heart failure. J Am Coll Cardiol 2000; 36: 838–44.
22. Hayashi M, Tsutamoto T, Wada A et al. Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents postinfarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction. Circulation 2003; 107: 2559–65.
23. Bender SB, DeMarco VG, Padilla J et al. Mineralocorticoid receptor antagonism treats obesity-associated cardiac diastolic dysfunction. Hypertension 2015; 65 (5): 1082–8.
24. Zannad F, McMurray JJ, Krum H et al., EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011; 364: 11–21.
25. Ademi Z, Pasupathi K, Krum H, Liew D. Cost effectiveness of eplerenone in patients with chronic heart failure. Am J Cardiovasc Drugs 2014; 14: 209–16.
26. Shah KB, Rao K, Sawyer R, Gottlieb SS. The adequacy of laboratory monitoring in patients treated with spironolactone for congestive heart failure. J Am Coll Cardiol 2005; 46: 845–9.
27. Juurlink DN, Mamdani MM, Lee DS et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 2004; 351: 543–51.
28. 2016 ESC Guidelines: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology. Eur Heart J 2016; 37: 2129–200. DOI: 10.1093/eurheartj/ehw128
29. Карпов Ю.А. Эплеренон: улучшение прогноза у больных с хронической сердечной недостаточностью ишемической этиологии. Атмосфера. Новости кардиологии. 2014; 2: 28–36.
[Karpov Iu.A. Eplerenon: uluchshenie prognoza u bol'nykh s khronicheskoi serdechnoi nedostatochnost'iu ishemicheskoi etiologii. Atmosfera. Novosti kardiologii. 2014; 2: 28–36 (in Russian).]
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1. Sumin A.N. Optimal'naia medikamentoznaia terapiia khronicheskoi serdechnoi nedostatochnosti: rol' antagonistov mineralokortikoidnykh retseptorov. RMZh. 2018; 11 (1): 71–5 (in Russian).
2. Zykov M.V., Zykova D.S., Kashtlap V.V. et al. Znachimost' mul'tifokal'nogo ateroskleroza dlia modifikatsii shkaly riska otdalennoi smertnosti GRACE u bol'nykh ostrym koronarnym sindromom s pod"emom segmenta ST. Ateroskleroz. 2012; 8 (1): 14–20 (in Russian).
3. Kosiagina D.D., Zavyrylina P.N., Sedykh D.Iu. et al. Faktory, assotsiirovannye s pozdnim obrashcheniem za meditsinskoi pomoshch'iu pri infarkte miokarda. Kompleksnye problemy serdechno-sosudistykh zabolevanii. 2017; 3: 104–12 (in Russian).
4. Komajda M, Cowie MR, Tavazzi L et al. QUALIFY Investigators. Physicians’ guideline adherence is associated with better prognosis in outpatients with heart failure with reduced ejection fraction: the QUALIFY international registry. Eur J Heart Fail 2017; 19 (11): 1414–23. DOI: 10.1002/ejhf.887
5. Giliarevskii S.R., Golshmid M.V., Kuz'mina I.M. Rol' antagonistov retseptorov al'dosterona v profilaktike i lechenii serdechno-sosudistykh i pochechnykh zabolevanii: real'nost' i perspektivy. Rus. med. zhurn. 2014; 23: 1689–98 (in Russian).
6. Nagarajan V, Chamsi-Pasha M, Tang WH. The role of aldosterone receptor antagonists in the management of heart failure: an update. Cleve Clin J Med 2012; 79: 631–39.
7. Edelmann F, Schmidt AG, Gelbrich G et al. Rationale and design of the “aldosterone receptor blockade in diastolic heart failure” trial: a double-blind, randomized, placebo-controlled, parallel group study to determine the effects of spironolactone on exercise capacity and diastolic function in patients with symptomatic diastolic heart failure (Aldo-DHF). Eur J Heart Fail 2010; 12: 874–82.
8. MacFadyen RJ, Lee AF, Morton JJ et al. How often are angiotensin II and aldosterone concentrations raised during chronic ACE inhibitor treatment in cardiac failure? Heart 1999; 82: 57–61.
9. Natsional'nye rekomendatsii OSSN, RKO i RNMOT. Serdechnaia nedostatochnost': khronicheskaia i ostraia dekompensirovannaia. Diagnostika, profilaktika i lechenie (5-i peresmotr). Moscow, 2018. DOI: 10.18087/cardio. 2475 (in Russian).
10. McKelvie RS, Yusuf S, Pericak D et al. Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation 1999; 100: 1056–64.
11. Vizzardi E, Nodari S, Caretta G et al. Effects of spironolactone on long-term mortality and morbidity in patients with heart failure and mild or no symptoms. Am J Med Sci 2014; 347 (4): 271–6.
12. Pitt B, Zannad F, Remme WJ et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999; 341: 709–17.
13. Jeunemaitre X, Chatellier G., Kreft-Jais C et al. Efficacy and tolerance of spironolactone in essential hypertension. Am J Cardiol 1987; 60: 820–5.
14. Sabbadin C, Calò LA, Armanini D. The story of spironolactones from 1957 to now: from sodium balance to inflammation. G Ital Nefrol 2016; 33 (Suppl. 66): 33.
15. De Gasparo M, Joss U, Ramjoué HP et al. Three new epoxy-spirolactone derivatives: characterization in vivo and in vitro. J Pharmacol Exp Ther 1987; 240: 650–6.
16. Pitt B, Remme W, Zannad F et al. Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348: 1309–21.
17. Pitt B, White H, Nicolau J et al., EPHESUS Investigators. Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure. J Am Coll Cardiol 2005; 46: 425–31.
18. Podzolkov V.I., Dragomiretskaia N.A. Antagonisty al'dosterona. Sovremennye predstavleniia o mekhanizmakh deistviia i effektakh spironolaktona. Ratsion. farmakoterapiia v kardiologii. 2017; 13 (2): 263–9. DOI: http://dx.doi.org/10.20996/1819-6446-2017-13-2-263-269 (in Russian).
19. Iqbal J, Fay R, Adlam D et al. Effect of eplerenone in percutaneous coronary intervention-treated post-myocardial infarction patients with left ventricular systolic dysfunction: a subanalysis of the EPHESUS trial. Eur J Heart Fail 2014; 16: 685–91.
20. Carillo S, Zhang Y, Fay R et al. Heart failure with systolic dysfunction complicating acute myocardial infarction – differential outcomes but similar eplerenone efficacy by ST-segment or non-ST-segment elevation: a post hoc substudy of the EPHESUS trial. Arch Cardiovasc Dis 2014; 107: 149–57.
21. Tsutamoto T, Wada A, Maeda K et al. Spironolactone inhibits the transcardiac extraction of aldosterone in patients with congestive heart failure. J Am Coll Cardiol 2000; 36: 838–44.
22. Hayashi M, Tsutamoto T, Wada A et al. Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents postinfarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction. Circulation 2003; 107: 2559–65.
23. Bender SB, DeMarco VG, Padilla J et al. Mineralocorticoid receptor antagonism treats obesity-associated cardiac diastolic dysfunction. Hypertension 2015; 65 (5): 1082–8.
24. Zannad F, McMurray JJ, Krum H et al., EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011; 364: 11–21.
25. Ademi Z, Pasupathi K, Krum H, Liew D. Cost effectiveness of eplerenone in patients with chronic heart failure. Am J Cardiovasc Drugs 2014; 14: 209–16.
26. Shah KB, Rao K, Sawyer R, Gottlieb SS. The adequacy of laboratory monitoring in patients treated with spironolactone for congestive heart failure. J Am Coll Cardiol 2005; 46: 845–9.
27. Juurlink DN, Mamdani MM, Lee DS et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 2004; 351: 543–51.
28. 2016 ESC Guidelines: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology. Eur Heart J 2016; 37: 2129–200. DOI: 10.1093/eurheartj/ehw128
29. Karpov Iu.A. Eplerenon: uluchshenie prognoza u bol'nykh s khronicheskoi serdechnoi nedostatochnost'iu ishemicheskoi etiologii. Atmosfera. Novosti kardiologii. 2014; 2: 28–36 (in Russian).
Авторы
В.В.Кашталап*1,2, Д.Ю.Седых1,3, О.Л.Барбараш1,2
1 ФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний». 650002, Россия, Кемерово, Сосновый б-р, д. 6;
2 ФГБОУ ВО «Кемеровский государственный медицинский университет» Минздрава России. 650029, Россия, Кемерово, ул. Ворошилова, д. 22а;
3 ГБУЗ «Кемеровский областной клинический кардиологический диспансер им. акад. Л.С.Барбараша». 650002, Россия, Кемерово, Сосновый б-р, д. 6
*v_kash@mail.ru
________________________________________________
Vasily V. Kashtalap*1,2, Darya Yu. Sedykh1,3, Olga L. Barbarash1,2
1 Research Institute for Complex Issues of Cardiovascular Diseases. 6, Sosnovyi bvd, Kemerovo, 650002, Russian Federation
2 Kemerovo State Medical University of the Ministry of Health of the Russian Federation. 22a, Voroshilova st., Kemerovo, 650056, Russian Federation;
3 L.S.Barbarash Kemerovo Regional Clinical Cardiology Dispensary. 6, Sosnovyi blvd, Kemerovo, 650002, Russian Federation
*v_kash@mail.ru