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Current Cardiology Reports
Erschienen in: Current Cardiology Reports 11/2020

01.11.2020 | New Therapies for Cardiovascular Disease (AA Bavry, Section Editor)

Mineralocorticoid Receptor Antagonists: a Comprehensive Review of Finerenone

verfasst von: Juan Simon Rico-Mesa, Averi White, Ashkan Ahmadian-Tehrani, Allen S. Anderson

Erschienen in: Current Cardiology Reports | Ausgabe 11/2020

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Abstract

Purpose of Review

We aim to review the mechanism of action and safety profile of mineralocorticoid receptor antagonists (MRAs) and discuss the differences between selective and non-selective MRAs. More specifically, finerenone is a new medication that is currently under investigation for its promising cardiovascular and nephrological effects.

Recent Findings

MRAs are well known for their utility in treating heart failure, refractory hypertension, and diverse nephropathies, namely, diabetic nephropathy. As their name denotes, MRAs inhibit the action of aldosterone at the mineralocorticoid receptor, preventing receptor activation. This prevents remodeling, decreases inflammation, and improves proteinuria. There are not significant differences in outcomes between selective and non-selective MRAs. A new selective MRA named finerenone (originally BAY 94-8862) has shown promising results in several trials (ARTS-HF and ARTS-DN) and smaller studies. Finerenone may have a dose-dependent benefit over older MRAs, decreasing rates of albuminuria and levels of BNP and NT-ProBNP without causing a significant increase in serum potassium levels. This medication is not yet approved as it is still in phase 3 clinical trials (FIGARO-DKD and FIDELIO-DKD trials).

Summary

MRAs are beneficial in several disease states. Newer medications, such as finerenone, should be considered in patients with heart failure and diabetic nephropathy who may benefit from a reduction in albuminuria and BNP/NT-ProBNP. Data surrounding finerenone are limited to date. However, results from ongoing clinical trials, as well as new trials to evaluate use in other pathologies, could validate the implementation of this medication in daily practice.
Literatur
1.
Santos RAS, Oudit GY, Verano-Braga T, Canta G, Steckelings UM, Bader M. The renin-angiotensin system: going beyond the classical paradigms. Am J Physiol Heart Circ Physiol. 2019;316(5):H958–H70.CrossRef
2.
Robert M, Carey SHP. Physiology and regulation of the renin–angiotensin–aldosterone system. In: Textbook of nephro-endocrinology. Second ed; 2018.
3.
Patel S, Rauf A, Khan H, Abu-Izneid T. Renin-angiotensin-aldosterone (RAAS): the ubiquitous system for homeostasis and pathologies. Biomed Pharmacother. 2017;94:317–25.CrossRef
4.
Tsuda K. Renin-angiotensin system and sympathetic neurotransmitter release in the central nervous system of hypertension. Int J Hypertens. 2012;2012:474870.PubMedPubMedCentral
5.
Te Riet L, van Esch JH, Roks AJ, van den Meiracker AH, Danser AH. Hypertension: renin-angiotensin-aldosterone system alterations. Circ Res. 2015;116(6):960–75.CrossRef
6.
Butterworth MB. Regulation of the epithelial sodium channel (ENaC) by membrane trafficking. Biochim Biophys Acta. 2010;1802(12):1166–77.CrossRef
7.
Delcayre C, Swynghedauw B. Molecular mechanisms of myocardial remodeling. The role of aldosterone. J Mol Cell Cardiol. 2002;34(12):1577–84.CrossRef
8.
White PC. Aldosterone: direct effects on and production by the heart. J Clin Endocrinol Metab. 2003;88(6):2376–83.CrossRef
9.
Stockand JD, Meszaros JG. Aldosterone stimulates proliferation of cardiac fibroblasts by activating Ki-RasA and MAPK1/2 signaling. Am J Physiol Heart Circ Physiol. 2003;284(1):H176–84.CrossRef
10.
Cicoira M, Zanolla L, Rossi A, Golia G, Franceschini L, Cabrini G, et al. Failure of aldosterone suppression despite angiotensin-converting enzyme (ACE) inhibitor administration in chronic heart failure is associated with ACE DD genotype. J Am Coll Cardiol. 2001;37(7):1808–12.
11.
Shaw JC. Spironolactone in dermatologic therapy. J Am Acad Dermatol. 1991;24(2 Pt 1):236–43.CrossRef
12.
Sica DA. Mineralocorticoid receptor antagonists for treatment of hypertension and heart failure. Methodist Debakey Cardiovasc J. 2015;11(4):235–9.CrossRef
13.
Zulian E, Sartorato P, Benedini S, Baro G, Armanini D, Mantero F, et al. Spironolactone in the treatment of polycystic ovary syndrome: effects on clinical features, insulin sensitivity and lipid profile. J Endocrinol Investig. 2005;28(1):49–53.
14.
Hauk L. Acne vulgaris: treatment guidelines from the AAD. Am Fam Physician. 2017;95(11):740–1.PubMed
15.
Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, 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(10):709–17.
16.
Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383–92.
17.
Bristow MR, Enciso JS, Gersh BJ, Grady C, Rice MM, Singh S, et al. Detection and management of geographic disparities in the TOPCAT trial: lessons learned and derivative recommendations. JACC Basic Transl Sci. 2016;1(3):180–9.CrossRef
18.
Butler J, Anstrom KJ, Felker GM, Givertz MM, Kalogeropoulos AP, Konstam MA, et al. Efficacy and safety of spironolactone in acute heart failure: the ATHENA-HF randomized clinical trial. JAMA Cardiol. 2017;2(9):950–8.
19.
Chrysostomou A, Becker G. Spironolactone in addition to ACE inhibition to reduce proteinuria in patients with chronic renal disease. N Engl J Med. 2001;345(12):925–6.CrossRef
20.
Sato A, Hayashi K, Saruta T. Antiproteinuric effects of mineralocorticoid receptor blockade in patients with chronic renal disease. Am J Hypertens. 2005;18(1):44–9.CrossRef
21.
Sato A, Hayashi K, Naruse M, Saruta T. Effectiveness of aldosterone blockade in patients with diabetic nephropathy. Hypertension. 2003;41(1):64–8.CrossRef
22.
Rossing K, Schjoedt KJ, Smidt UM, Boomsma F, Parving HH. Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy: a randomized, double-masked, cross-over study. Diabetes Care. 2005;28(9):2106–12.CrossRef
23.
Shufelt CL, Bairey Merz CN. Contraceptive hormone use and cardiovascular disease. J Am Coll Cardiol. 2009;53(3):221–31.CrossRef
24.
Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348(14):1309–21.
25.
Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11–21.
26.
Derosa G, Maffioli P, Scelsi L, Bestetti A, Vanasia M, Cicero AFG, et al. Canrenone on cardiovascular mortality in congestive heart failure: CanrenOne eFFects on cardiovascular mortality in patiEnts with congEstIve hearT failure: the COFFEE-IT study. Pharmacol Res. 2019;141:46–52.
27.
Bianchi S, Bigazzi R, Campese VM. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int. 2006;70(12):2116–23.CrossRef
28.
Alexandrou ME, Papagianni A, Tsapas A, Loutradis C, Boutou A, Piperidou A, et al. Effects of mineralocorticoid receptor antagonists in proteinuric kidney disease: a systematic review and meta-analysis of randomized controlled trials. J Hypertens. 2019;37(12):2307–24.
29.
Navaneethan SD, Nigwekar SU, Sehgal AR, Strippoli GF. Aldosterone antagonists for preventing the progression of chronic kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2009;4(3):542–51.CrossRef
30.
Hou FF, Xie D, Zhang X, Chen PY, Zhang WR, Liang M, et al. Renoprotection of optimal antiproteinuric doses (ROAD) study: a randomized controlled study of benazepril and losartan in chronic renal insufficiency. J Am Soc Nephrol. 2007;18(6):1889–98.
31.
Hou FF, Zhou QG. Optimal dose of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker for renoprotection. Nephrology (Carlton). 2010;15(Suppl 2):57–60.CrossRef
32.
Currie G, Taylor AH, Fujita T, Ohtsu H, Lindhardt M, Rossing P, et al. Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: a systematic review and meta-analysis. BMC Nephrol. 2016;17(1):127.CrossRef
33.
Epstein M, Williams GH, Weinberger M, Lewin A, Krause S, Mukherjee R, et al. Selective aldosterone blockade with eplerenone reduces albuminuria in patients with type 2 diabetes. Clin J Am Soc Nephrol. 2006;1(5):940–51.
34.
Tsuboi N, Kawamura T, Okonogi H, Ishii T, Hosoya T. The long-term antiproteinuric effect of eplerenone, a selective aldosterone blocker, in patients with non-diabetic chronic kidney disease. J Renin-Angiotensin-Aldosterone Syst. 2012;13(1):113–7.
35.
Ando K, Ohtsu H, Uchida S, Kaname S, Arakawa Y, Fujita T, et al. Anti-albuminuric effect of the aldosterone blocker eplerenone in non-diabetic hypertensive patients with albuminuria: a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2014;2(12):944–53.CrossRef
36.
Tylicki L, Rutkowski P, Renke M, Larczynski W, Aleksandrowicz E, Lysiak-Szydlowska W, et al. Triple pharmacological blockade of the renin-angiotensin-aldosterone system in nondiabetic CKD: an open-label crossover randomized controlled trial. Am J Kidney Dis. 2008;52(3):486–93.CrossRef
37.
38.
Hellal-Levy C, Fagart J, Souque A, Wurtz JM, Moras D, Rafestin-Oblin ME. Crucial role of the H11-H12 loop in stabilizing the active conformation of the human mineralocorticoid receptor. Mol Endocrinol. 2000;14(8):1210–21.CrossRef
39.
• Ruilope LM, Agarwal R, Anker SD, Bakris GL, Filippatos G, Nowack C, et al. Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial. Am J Nephrol. 2019;50(5):345–56. This trial is currently on-going, and it intends to assess the efficacy and safety of finerenone in patients with diabetes mellitus and diabetic nephropathy in terms of decreasing cardiovascular death and non-cardiovascular fatal events.CrossRef
40.
•• Filippatos G, Anker SD, Bohm M, Gheorghiade M, Kober L, Krum H, et al. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease. Eur Heart J. 2016;37(27):2105–14. Findings from this trial suggest a possible benefit in worsening heart failure determined by NT-proBNP reduction with eplerenone 10–20 mg orally once daily over eplerenone in patients with diabetes and CKD.CrossRef
41.
•• Bakris GL, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA. 2015;314(9):884–94. This study found that among patients with diabetic nephropathy receiving ACEi/ARB, the addition of finerenone showed a decrease in the UACR.
42.
Pitt B, Kober L, Ponikowski P, Gheorghiade M, Filippatos G, Krum H, et al. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J. 2013;34(31):2453–63.
43.
•• Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Nowack C, et al. Design and baseline characteristics of the finerenone in reducing kidney failure and disease progression in diabetic kidney disease trial. Am J Nephrol. 2019;50(5):333–44. This study is a phase 3 clinical trial with a similar study design to the FIGARO-DKD trial, which aims to assess the efficacy and safety of finerenone, which assessed the progression of kidney failure in diabetic patients with diabetic nephropathy.CrossRef
44.
Heinig R, Kimmeskamp-Kirschbaum N, Halabi A, Lentini S. Pharmacokinetics of the novel nonsteroidal mineralocorticoid receptor antagonist Finerenone (BAY 94-8862) in individuals with renal impairment. Clin Pharmacol Drug Dev. 2016;5(6):488–501.CrossRef
45.
Kolkhof P, Nowack C, Eitner F. Nonsteroidal antagonists of the mineralocorticoid receptor. Curr Opin Nephrol Hypertens. 2015;24(5):417–24.CrossRef
46.
Lentini S, Heinig R, Kimmeskamp-Kirschbaum N, Wensing G. Pharmacokinetics, safety and tolerability of the novel, selective mineralocorticoid receptor antagonist finerenone—results from first-in-man and relative bioavailability studies. Fundam Clin Pharmacol. 2016;30(2):172–84.CrossRef
47.
Sato N, Ajioka M, Yamada T, Kato M, Myoishi M, Yamada T, et al. A randomized controlled study of finerenone vs. eplerenone in Japanese patients with worsening chronic heart failure and diabetes and/or chronic kidney disease. Circ J. 2016;80(5):1113–22.
48.
Pei H, Wang W, Zhao D, Wang L, Su GH, Zhao Z. 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.CrossRef
49.
Dutzmann J, Musmann RJ, Haertle M, Daniel JM, Sonnenschein K, Schafer A, et al. The novel mineralocorticoid receptor antagonist finerenone attenuates neointima formation after vascular injury. PLoS One. 2017;12(9):e0184888.CrossRef
50.
Gonzalez-Blazquez R, Somoza B, Gil-Ortega M, Martin Ramos M, Ramiro-Cortijo D, Vega-Martin E, et al. Finerenone attenuates endothelial dysfunction and albuminuria in a chronic kidney disease model by a reduction in oxidative stress. Front Pharmacol. 2018;9:1131.CrossRef
51.
Kolkhof PKA, Baerfacker L, Hartmann E, Schaefer S. Improved survival and nephroprotection in hypertensive rats by BAY 94-8862, a novel non-steroidal mineralocorticoid receptor antagonist. Eur Heart J. 2020;33:978–9.
52.
53.
Metadaten
Titel
Mineralocorticoid Receptor Antagonists: a Comprehensive Review of Finerenone
verfasst von
Juan Simon Rico-Mesa
Averi White
Ashkan Ahmadian-Tehrani
Allen S. Anderson
Publikationsdatum
01.11.2020
Verlag
Springer US
Erschienen in
Current Cardiology Reports / Ausgabe 11/2020
Print ISSN: 1523-3782
Elektronische ISSN: 1534-3170
DOI
https://doi.org/10.1007/s11886-020-01399-7

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