Eplerenone administration opportunities in heart failure from the standpoint of evidence-based medicine
V.N. Larina
Pirogov Russian National Research Medical University, Moscow
The article discusses opportunities for edema syndrome correction in chronic heart failure (CHF) and high activity of renin-angiotensin-aldosterone system in the abstract form. The following issues are highlighted: aldosterone synthesis, its physiological action and its role in the development of hypervolemia, fluid retention, and formation of cardiac fibrosis (one of the most important elements of cardiac remodeling and CHF progression). The mineralocorticoid receptor antagonists (MRAs) effects are described, including reduction of myocardial interstitial and perivascular fibrosis and its pathological remodeling, left ventricular (LV) hypertrophy, and endothelial function improvement. The data on highly selective MRA eplerenone (EPHESUS and EMPHASIS-HF) is presented in the randomized clinical study results and their subsequent analysis. It was shown that eplerenone administration in patients with systolic LV dysfunction and heart failure contributed to a reduction in overall mortality, cardiovascular mortality, the likelihood of sudden cardiac death, and hospital admission rate. A comparison between the eplerenone clinical effects and the nonselective MRA spironolactone effects, the main adverse events of their use and correction methods, as well as the possibilities and prospects of eplerenone administration in CHF with both low and preserved LV EF are considered in this article.
Keywords: chronic heart failure, systolic dysfunction, aldosterone, mineralocorticoid receptor antagonists, eplerenone.
For citation: Larina V.N. Eplerenone administration opportunities in heart failure from the standpoint of evidence-based medicine. RMJ. Medical Review. 2019;1(II):87–92.
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37. Давыдова С.С. Петлевые диуретики и резистентная к терапии хроническая сердечная недостаточность. РМЖ. 2014;12:934. [Davydova S.S. Loop diuretics and chronic heart failure resistant to therapy. RMJ. 2014;12:934 (in Russ.)].
38. Ademi Z., Pasupathi K., Krum H., Liew D. Cost effectiveness of eplerenone in patients with chronic heart failure. Am J Cardiovasc Drugs. 2014;14:209–216. DOI: 10.1007/s40256-014-0066-3.
2. Mullens W., Damman K., Harjola V.P. et al. The use of diuretics in heart failure with congestion — a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2019;21:137–155. DOI:10.1002/ejhf.1369.
3. Thibodeau J., Turer A., Gualano S. et al. Characterization of a novel symptom of advanced heart failure: bendopnea. JACC Heart Fail. 2014;2:24–31. DOI: 10.1016/j.jchf.2013.07.009.
4. Thibodeau J., Jenny B., Maduka J. et al. Bendopnea and risk of adverse clinical outcomes in ambulatory patients with systolic heart failure. Am Heart J. 2017;183:102–107. DOI: 10.1016/j.ahj.2016.09.011.
5. Марев В.Ю., Фомин И.В., Агев Ф.Т. и др. Клинические рекомендации ОССН — РКО — РНМОТ. Сердечная недостаточность: хроническая (ХСН) и острая декомпенсированная (ОДСН). Диагностика, профилактика и лечение. Кардиология. 2018;58(6):8–164. [Mareev V.Y., Fomin I.V., Ageev F.T. et al. Russian Heart Failure Society, Russian Society of Cardiology. Russian Scientific Medical Society of Internal Medicine Guidelines for Heart failure: chronic (CHF) and acute decompensated (ADHF). Diagnosis, prevention and treatment. Cardiology. 2018;58(6):8–158 (in Russ.)]. https://doi.org/10.18087/cardio.2475.
6. Yancy C., Jessup M., Bozkurt B. et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. J of Am Coll Card. 2017;23682. DOI:10.1016/j.jacc.2017.04.025.
7. Zannad F., McMurray J., 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. DOI: 10.1056/NEJMoa1009492.
8. Weber K. Aldosterone in congestive heart failure. N Engl J Med. 2001;345:1689–1697. DOI:10.1056/NEJMra000050.
9. Kassahn K., Ragan M., Funder J. Mineralocorticoid receptors: Evolutionary and pathophysiological considerations. Endocrinology. 2011;152:1883–1890. DOI.org/10.1210/en.2010–1444.
10. Chou C., Hung C., Liao C. et al. The TAIPAI Study Group; IL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis. Cardiovascular Research. 2018;114(5):690–702. DOI: 10.1093/cvr/cvy013.
11. Vizzardi E., Regazzoni V., Caretta G. et al. Mineralocorticoid receptor antagonist in heart failure: Past, present and future perspectives. IJC Heart and Vessels. 2014;3:6–14. DOI: 10.1016/j.ijchv.2014.03.005.
12. Hannich M., Wallaschofski H., Nauck M. et al. Physiological Aldosterone Concentrations Are Associated with Alterations of Lipid Metabolism: Observations from the General Population. Int J Endocrinol. 2018;2018:4128174. DOI:10.1155/2018/4128174.
13. Vaziri N.D. Disorders of lipid metabolism in nephrotic syndrome: mechanisms and consequences. Kidney International. 2016;90(1):41–52. DOI: 10.1016/j.kint.2016.02.026.
14. Danjuma M., Mukherjee I., Makaronidis J., Osula S. Converging indications of aldosterone antagonists (spironolactone and eplerenone): a narrative review of safety profiles. Curr Hypertens Rep. 2014;16:414. DOI: 10.1007/s11906-013-0414-8.
15. Pandey A., Garg S., Matulevicius S. Effect of Mineralocorticoid Receptor Antagonists on Cardiac Structure and Function in Patients With Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction: A Meta-Analysis and Systematic Review. J Am Heart Assoc. 2015;4:e002137. DOI: 10.1161/JAHA.115.002137.
16. Chen Y., Wang H., Lu Y. et al. Effects of mineralocorticoid receptor antagonists in patients with preserved ejection fraction: a meta-analysis of randomized clinical trials. BMC Medicine. 2015;13:10. DOI: 10.1186/s12916-014-0261-8.
17. Gilpin T., Laird A. Cardiorenal medicine: challenges for the decade ahead. Br J Cardiol. 2016;23:1. DOI:10.5837/bjc.2016.005.
18. Pei H., Wang W., Zhao D. et al. The use of a novel non-steroidal mineralocorticoid receptor antagonist finerenone for the treatment of chronic heart failure: A systematic review and meta-analysis. Medicine (Baltimore). 2018;97(16):e0254. DOI: 10.1097/MD.0000000000010254.
19. Pitt B., Remme W., Zannad F. et al. for the 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;348:1309–1321. DOI:10.1056/NEJMoa030207.
20. Collier T., Pocock S., McMurray J. et al. The impact of eplerenone at different levels of risk in patients with systolic heart failure and mild symptoms: insight from a novel risk score for prognosis derived from the EMPHASIS-HF trial. Eur. Heart. J. 2013;34:2823–2829. DOI: 10.1093/eurheartj/eht247.
21. Lainscak M., Pelliccia F., Rozano G. et al. Safety profile of mineralocorticoid receptor antagonists: Spironolactone and eplerenone. International Journal of Cardiology. 2015;200:25–29. DOI: 10.1016/j.ijcard.2015.05.127.
22. Lazich I., Bakris G.L. Prediction and management of hyperkalemia across the spectrum of chronic kidney disease. Semin Nephrol. 2014;34:333–339. DOI: 10.1016/j.semnephrol.2014.04.008.
23. McMurray J. Improving outcomes in heart failure: a personal perspective. Eur Heart J. 2015;36:3467–3470. DOI: 10.1093/eurheartj/ehv565.
24. Burnett H., Earley A., Voors A. et al. Thirty years of evidence on the efficacy of drug treatments for chronic heart failure with reduced ejection fraction: a network meta-analysis. Circ Heart Fail. 2017;10:e003529. DOI: 10.1161/CIRCHEARTFAILURE.116.003529.
25. Ko B., Bakris G. The renin-angiotensin-aldosterone system and the kidney. A.K. Singh, G.H. Williams, eds. Textbook of Nephro-Endocrinology. 2nd ed. New York: Elsevier Press. 2018. DOI: 10.1038/jhh.2014.125.
26. Thorvaldsen T., Benson L., Dahlstrom U. et al. Use of evidence-based therapy and survival in heart failure in Sweden 2003–2012. Eur J Heart Fail 2016;18:503–511. DOI: 10.1002/ejhf.496.
27. Rossignol P., Dobre D., McMurray J. et al. Incidence, determinants, and prognostic significance of hyperkalemia and worsening renal function in patients with heart failure receiving the mineralocorticoid receptor antagonist eplerenone or placebo in addition to optimal medical therapy: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). Circ Heart Fail. 2014;7:51–58. DOI: 10.1161/CIRCHEARTFAILURE.113.000792.
28. Eschalier R., McMurray J., Swedberg K. et al. Safety and efficacy of eplerenone in patients at high risk for hyperkalemia and/or worsening renal function: analyses of the EMPHASIS-HF Study Subgroups (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure). J Am Coll Cardiol. 2013;62:1585–1593. DOI: 10.1016/j.jacc.2013.04.086.
29. Mamas M., Sperrin M., Watson M. et al. Do patients have worse outcomes in heart failure than in cancer? A primary care-based cоhort study with 10-year follow-up in Scotland. Eur J Heart Fail. 2017;19:1095–1104.
30. Borlaug B., Paulus W. Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J. 2011;32:670–679. DOI: 10.1093/eurheartj/ehq426.
31. Mach G., Ledwidge M., Watson C. et al. Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone. J Am Coll Cardiol. 2009;54:1674–1682. DOI: 10.1016/j.jacc.2009.08.021.
32. Kampourides N., Tziakas D., Chalikias G. et al. Usefulness of matrix metalloproteinase-9 plasma levels to identify patients with preserved left ventricular systolic function after acute myocardial infarction who could benefit from eplerenone. Am J Cardiol. 2012;110:1085–1091. DOI: 10.1016/j.amjcard.2012.05.049.
33. Скворцов А.А. Антагонисты минералокортикоидных рецепторов в лечении больных с хронической сердечной недостаточностью и инфарктом миокарда: современный взгляд на старую проблему. РМЖ. 2017;4:257–264. [Skvortsov A.A. Mineralocorticoid receptor antagonists in the treatment of patients with chronic heart failure and myocardial infarction: a modern view on the old problem. RMJ. 2017;4:257–264 (in Russ.)].
34. Овчинников А.Г. Роль блокаторов ангиотензиновых рецепторов в лечении хронической сердечной недостаточности. РМЖ. 2017;20:1444–1451. [Ovchinnikov A.G. The role of angiotensin receptor blockers in the treatment of chronic heart failure. RMJ. 2017;20:1444–1451 (in Russ.)].
35. Галявич А.С. Диагностика и лечение хронической сердечной недостаточности сегодня. РМЖ. 2014;12:867. [Galyavich A.S. Diagnosis and treatment of chronic heart failure today. RMJ. 2014;12:867 (in Russ.)].
36. Ахметзянова Э.Х., Гайнитдинова В.В., Шарафутдинова Л.А. Ведение пациентов с хронической сердечной недостаточностью с сохранной систолической функцией на фоне тяжелого течения ХОБЛ в фазе обострения. РМЖ. 2014;2:138. [Akhmetzyanova E.Kh., Gainitdinova V.V., Sharafutdinova L.A. Maintaining patients with chronic heart failure with intact systolic function on the background of severe COPD in the acute phase. RMJ. 2014;2:138 (in Russ.)].
37. Давыдова С.С. Петлевые диуретики и резистентная к терапии хроническая сердечная недостаточность. РМЖ. 2014;12:934. [Davydova S.S. Loop diuretics and chronic heart failure resistant to therapy. RMJ. 2014;12:934 (in Russ.)].
38. Ademi Z., Pasupathi K., Krum H., Liew D. Cost effectiveness of eplerenone in patients with chronic heart failure. Am J Cardiovasc Drugs. 2014;14:209–216. DOI: 10.1007/s40256-014-0066-3.
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