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Значение блокаторов минералокортикоидных рецепторов в лечении хронической сердечной недостаточности
Кириченко А.А. Значение блокаторов минералокортикоидных рецепторов в лечении хронической сердечной недостаточности. Consilium Medicum. 2017; 19 (5): 59–63.
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Kirichenko A.A. The mineralocorticoid receptor blockers in the treatment of chronic heart failure. Consilium Medicum. 2017; 19 (5): 59–63.
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Аннотация
Негативная роль вторичного альдостеронизма при хронической сердечной недостаточности (ХСН) известна давно, но высокий уровень альдостерона связывался исключительно с задержкой жидкости в организме и электролитным дисбалансом. За последние десятилетия накопились данные о влиянии гиперальдостеронизма при ХСН на развитие фиброза миокарда, периваскулярного воспаления, дисфункции эндотелия, стимуляцию апоптоза кардиомиоцитов, прогрессирующее ухудшение функции сердца, развитие жизнеугрожающих аритмий. Исследования с дополнительным назначением при ХСН антагонистов альдостерона выявили достоверное снижение риска внезапной сердечной смерти и смерти от прогрессирования ХСН, а также частоты госпитализаций по сердечно-сосудистым причинам. Согласно современным рекомендациям, начиная со II функционального класса целесообразно применение тройной нейрогормональной блокады – комбинации блокатора ренин-ангиотензиновой системы (ингибитора ангиотензипревращающего фермента или блокатора рецепторов ангиотензина) с b-адреноблокатором и антагонистом рецепторов альдостерона. Такая схема ведения больного с ХСН позволяет улучшить не только качество жизни тяжелых больных, но и прогноз.
Ключевые слова: блокаторы минералокортикоидных рецепторов, альдостерон, спиронолактон, эплеренон, хроническая сердечная недостаточность.
Ключевые слова: блокаторы минералокортикоидных рецепторов, альдостерон, спиронолактон, эплеренон, хроническая сердечная недостаточность.
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The negative role of secondary aldosteronism associated with CHF is known for a long time. But the high level of aldosterone concentration is exclusively associated with water retention and electrolyte imbalance. Over the past decade we have accumulated data concerning the impact of hyperaldosteronism associated with CHF on the development of cardiac fibrosis, perivascular inflammation, endothelial dysfunction, stimulation of apoptosis and cardiomyocytes, progressive impairment of heart function, the development of life-threatening arrhythmias. The studies concerning the additional appointment of aldosterone antagonists in patients with CHF have revealed the significant reduction in the risk of sudden cardiac death and death from the progression of CHF, as well as the frequency of cardiovascular hospitalizations. According to the current recommendations, starting from the functional class II it is advisable to use a triple neurohormonal blockade – the combination of renin-angiotensin system blockers (IAPF) and beta blockers and aldosterone receptor antagonist. Such a scheme of managing the patient with CHF can improve not only the quality of life of serious patients, but also prognosis.
Key words: mineralocorticoid receptor blockers, aldosterone, spironolactone, eplerenone, chronic heart failure.
Полный текст
Список литературы
1. Helman SI, Liu X, Baldwin K et al. Time-dependent stimulation by aldosterone of blocker-sensitive ENaCs in A6 epithelia. Am J Physiol Cell Physiol 1998; 274: C947–C957.
2. Booth E, Johnson JP, Stockand JD. Aldosterone. Adv Physiol Educ 2002; 26: 8–23.
3. Falkenstein E, Tillmann HC, Christ M et al. Multiple actions of steroid hormones – a focus on rapid, nongenomic effects. Pharmacol Rev 2000; 52: 513–56.
4. Sato A, Funder JW. High glucose stimulates aldosterone-induced hypertrophy via type I mineralocorticoid receptors in neonatal rat cardiomyocytes. Endocrinol 1996; 137: 4145–53.
5. Tsutamoto T, Wadw A, Maeda K et al. Effect of spironolactone on Plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure. J Am Col Cardiol 2001; 37: 1228–33.
6. Zannand F, Alla F, Dousset B et al. Limination of excessive extracellular matrix turnover may contribute to survaival benefit of spironolacton therapy in patients with congestive heart failure. Insifhts from the randomized aldactone evaluated study (Rales). Circulation 2000; 102: 2700–6.
7. McFaiden R, Barr C, Struthers A. Aldosterone blocade reduces vascular collagen turnover, improves heart rate variability and reduces early morning rise in heart rate in heart failure patients. Cardiovasc Res 1997; 35: 30–4.
8. Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium: fibrosis and renin-angiotensin-aldosterone system. Circulation 1991; 83: 1849–65.
9. Mano A, Tatsumi T, Shiraishi J et al. Aldosterone directly induces myocyte apoptosis through calcineurin-dependent pathways. Circulation 2004; 110: 317–23.
10. 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.
11. 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.
12. Tang WH, Vagelos RH, Yee YG et al. Neurohormonal and clinical responses to high-versus low-dose enalapril therapy in chronic heart failure. J Am Coll Cardiol 2002; 39: 70–8.
13. Weber KT. Aldosterone in congestive heart failure. N Engl J Med 2001; 345: 1689–97.
14. 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.
15. 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.
16. Сытник Н.В., Кокорин В.А., Люсов В.А. и др. Активность РААС и САС у больных в отдаленные сроки после первичного инфаркта миокарда. Рос. кардиол. журн. 2009; 4: 17–22.
17. Palmer BR, Pilbrow AP, Frampton CM et al. Plasma aldosterone levels during hospitalization are predictive of survival post-myocardial infarction. Eur Heart J 2008; 29: 2489–96.
18. 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.
19. Adamopoulos Ch, Ahmed A, Fay R et al; the EPHESUS Investigators. Timing of eplerenone initiation and outcomes in patients with heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction: insights from the EPHESUS trial. Eur J Heart Fail 2009; 11: 1099–105.
20. 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.
21. 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.
22. Zannad F, McMurray JJ, Krum Н et al; EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011; 364: 11–21.
23. Edelmann F, Wachter R, Schmidt AG et al. Aldo-DHF Investigators. Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial. JAMA 2013; 309: 781–91.
24. Pfeffer МА, McKinlay S, Pitt В et al; ТОРСАТ Investigators. Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone anTagonist (ТОРСАТ). Abstracts of the American Heart Association Scientific Sessions 2013; November 16–20, 2013; Dallas, Texas.
25. Sica DA. The risks and benefits of therapy with aldosterone receptor antagonist therapy. Curr Drug Saf 2007; 2: 71–7.
26. Jeunemaitre X, Chatellier G, Kreft-Jais C et al. Efficacy and tolerance of spironolactone in essential hypertension. Am J Cardiol 1987; 60: 820–5.
2. Booth E, Johnson JP, Stockand JD. Aldosterone. Adv Physiol Educ 2002; 26: 8–23.
3. Falkenstein E, Tillmann HC, Christ M et al. Multiple actions of steroid hormones – a focus on rapid, nongenomic effects. Pharmacol Rev 2000; 52: 513–56.
4. Sato A, Funder JW. High glucose stimulates aldosterone-induced hypertrophy via type I mineralocorticoid receptors in neonatal rat cardiomyocytes. Endocrinol 1996; 137: 4145–53.
5. Tsutamoto T, Wadw A, Maeda K et al. Effect of spironolactone on Plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure. J Am Col Cardiol 2001; 37: 1228–33.
6. Zannand F, Alla F, Dousset B et al. Limination of excessive extracellular matrix turnover may contribute to survaival benefit of spironolacton therapy in patients with congestive heart failure. Insifhts from the randomized aldactone evaluated study (Rales). Circulation 2000; 102: 2700–6.
7. McFaiden R, Barr C, Struthers A. Aldosterone blocade reduces vascular collagen turnover, improves heart rate variability and reduces early morning rise in heart rate in heart failure patients. Cardiovasc Res 1997; 35: 30–4.
8. Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium: fibrosis and renin-angiotensin-aldosterone system. Circulation 1991; 83: 1849–65.
9. Mano A, Tatsumi T, Shiraishi J et al. Aldosterone directly induces myocyte apoptosis through calcineurin-dependent pathways. Circulation 2004; 110: 317–23.
10. 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.
11. 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.
12. Tang WH, Vagelos RH, Yee YG et al. Neurohormonal and clinical responses to high-versus low-dose enalapril therapy in chronic heart failure. J Am Coll Cardiol 2002; 39: 70–8.
13. Weber KT. Aldosterone in congestive heart failure. N Engl J Med 2001; 345: 1689–97.
14. 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.
15. 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.
16. Сытник Н.В., Кокорин В.А., Люсов В.А. и др. Активность РААС и САС у больных в отдаленные сроки после первичного инфаркта миокарда. Рос. кардиол. журн. 2009; 4: 17–22.
17. Palmer BR, Pilbrow AP, Frampton CM et al. Plasma aldosterone levels during hospitalization are predictive of survival post-myocardial infarction. Eur Heart J 2008; 29: 2489–96.
18. 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.
19. Adamopoulos Ch, Ahmed A, Fay R et al; the EPHESUS Investigators. Timing of eplerenone initiation and outcomes in patients with heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction: insights from the EPHESUS trial. Eur J Heart Fail 2009; 11: 1099–105.
20. 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.
21. 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.
22. Zannad F, McMurray JJ, Krum Н et al; EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011; 364: 11–21.
23. Edelmann F, Wachter R, Schmidt AG et al. Aldo-DHF Investigators. Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial. JAMA 2013; 309: 781–91.
24. Pfeffer МА, McKinlay S, Pitt В et al; ТОРСАТ Investigators. Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone anTagonist (ТОРСАТ). Abstracts of the American Heart Association Scientific Sessions 2013; November 16–20, 2013; Dallas, Texas.
25. Sica DA. The risks and benefits of therapy with aldosterone receptor antagonist therapy. Curr Drug Saf 2007; 2: 71–7.
26. Jeunemaitre X, Chatellier G, Kreft-Jais C et al. Efficacy and tolerance of spironolactone in essential hypertension. Am J Cardiol 1987; 60: 820–5.
________________________________________________
1. Helman SI, Liu X, Baldwin K et al. Time-dependent stimulation by aldosterone of blocker-sensitive ENaCs in A6 epithelia. Am J Physiol Cell Physiol 1998; 274: C947–C957.
2. Booth E, Johnson JP, Stockand JD. Aldosterone. Adv Physiol Educ 2002; 26: 8–23.
3. Falkenstein E, Tillmann HC, Christ M et al. Multiple actions of steroid hormones – a focus on rapid, nongenomic effects. Pharmacol Rev 2000; 52: 513–56.
4. Sato A, Funder JW. High glucose stimulates aldosterone-induced hypertrophy via type I mineralocorticoid receptors in neonatal rat cardiomyocytes. Endocrinol 1996; 137: 4145–53.
5. Tsutamoto T, Wadw A, Maeda K et al. Effect of spironolactone on Plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure. J Am Col Cardiol 2001; 37: 1228–33.
6. Zannand F, Alla F, Dousset B et al. Limination of excessive extracellular matrix turnover may contribute to survaival benefit of spironolacton therapy in patients with congestive heart failure. Insifhts from the randomized aldactone evaluated study (Rales). Circulation 2000; 102: 2700–6.
7. McFaiden R, Barr C, Struthers A. Aldosterone blocade reduces vascular collagen turnover, improves heart rate variability and reduces early morning rise in heart rate in heart failure patients. Cardiovasc Res 1997; 35: 30–4.
8. Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium: fibrosis and renin-angiotensin-aldosterone system. Circulation 1991; 83: 1849–65.
9. Mano A, Tatsumi T, Shiraishi J et al. Aldosterone directly induces myocyte apoptosis through calcineurin-dependent pathways. Circulation 2004; 110: 317–23.
10. 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.
11. 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.
12. Tang WH, Vagelos RH, Yee YG et al. Neurohormonal and clinical responses to high-versus low-dose enalapril therapy in chronic heart failure. J Am Coll Cardiol 2002; 39: 70–8.
13. Weber KT. Aldosterone in congestive heart failure. N Engl J Med 2001; 345: 1689–97.
14. 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.
15. 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.
16. Сытник Н.В., Кокорин В.А., Люсов В.А. и др. Активность РААС и САС у больных в отдаленные сроки после первичного инфаркта миокарда. Рос. кардиол. журн. 2009; 4: 17–22.
17. Palmer BR, Pilbrow AP, Frampton CM et al. Plasma aldosterone levels during hospitalization are predictive of survival post-myocardial infarction. Eur Heart J 2008; 29: 2489–96.
18. 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.
19. Adamopoulos Ch, Ahmed A, Fay R et al; the EPHESUS Investigators. Timing of eplerenone initiation and outcomes in patients with heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction: insights from the EPHESUS trial. Eur J Heart Fail 2009; 11: 1099–105.
20. 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.
21. 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.
22. Zannad F, McMurray JJ, Krum Н et al; EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011; 364: 11–21.
23. Edelmann F, Wachter R, Schmidt AG et al. Aldo-DHF Investigators. Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial. JAMA 2013; 309: 781–91.
24. Pfeffer МА, McKinlay S, Pitt В et al; ТОРСАТ Investigators. Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone anTagonist (ТОРСАТ). Abstracts of the American Heart Association Scientific Sessions 2013; November 16–20, 2013; Dallas, Texas.
25. Sica DA. The risks and benefits of therapy with aldosterone receptor antagonist therapy. Curr Drug Saf 2007; 2: 71–7.
26. Jeunemaitre X, Chatellier G, Kreft-Jais C et al. Efficacy and tolerance of spironolactone in essential hypertension. Am J Cardiol 1987; 60: 820–5.
Авторы
А.А.Кириченко
ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России. 125993, Россия, Москва, ул. Баррикадная, д. 2/1
andrey.apollonovich@yandex.ru
ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России. 125993, Россия, Москва, ул. Баррикадная, д. 2/1
andrey.apollonovich@yandex.ru
________________________________________________
A.A.Kirichenko
Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation. 125993, Russian Federation, Moscow, ul. Barrikadnaia, d. 2/1
andrey.apollonovich@yandex.ru
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