The changing landscape of mineralocorticoid receptor antagonists – finerenone in cardiovascular and renal health

Adam Piasecki; Magdalena Sitnik; Jakub Olszewski; Maciej Bara; Katarzyna Herjan; Piotr Armański

doi:10.56782/pps.181

Data publikacji : 2024-02-13

Tom 22 Nr 1 (2024)

The changing landscape of mineralocorticoid receptor antagonists – finerenone in cardiovascular and renal health

Adam Piasecki

Magdalena Sitnik

Jakub Olszewski

Maciej Bara

Katarzyna Herjan

Piotr Armański

DOI: https://doi.org/10.56782/pps.181

Abstrakt

Finerenone is a novel non-steroidal mineralocorticoid receptor antagonist (MRA) with high selectivity and affinity to mineralocorticoid receptor (MR). Steroidal MRAs, like spironolactone and eplerenone, have been in use for decades. They have an established position in the management of hypertension and heart failure with reduced ejection fraction (HFrEF). There are studies showing that MR antagonism has anti-inflammatory and anti-fibrotic effects resulting in cardiovascular and renal protection. However, broader use of steroidal MRAs is seriously limited by antiandrogenic side effects and the risk of hyperkalemia. The differences in structure as well as pharmacokinetic and pharmacodynamic properties between steroidal and non-steroidal MRAs result in reduced risk of side effects while offering the benefit of cardiorenal protection. Finerenone is currently the only non-steroidal MRA approved by European Medicines Agency (EMA). It is indicated for patients with chronic kidney disease (CKD) with albuminuria and type 2 diabetes mellitus (DM2). Several studies showed a reduction of the risk of cardiovascular and renal events in this group of patients compared to placebo. The risk of hyperkalemia was increased resulting in discontinuation of treatment in more patients than placebo, but the risk of serious adverse events did not differ significantly. The other indications for finerenone, including heart failure (HF) management, are currently being researched.

Inne teksty tego samego autora

Katarzyna Kozon, Małgorzata Krzyżanowska, Jakub Olszewski, Andrzej Patyra, Spinal muscular atrophy – the effectiveness of treatment and new therapeutic possibilities for selected groups of patients in Poland , Prospects in Pharmaceutical Sciences: Tom 21 Nr 2 (2023)
Jakub Olszewski, Katarzyn Kozon, Andrzej Patyra, Flozins in heart failure – a new reimbursement indication , Prospects in Pharmaceutical Sciences: Tom 20 Nr 1 (2022)
Adam Piasecki, Non-vitamin K antagonist oral anticoagulants (NOAC) in nonvalvular atrial fibrillation – in-group comparison , Prospects in Pharmaceutical Sciences: Tom 20 Nr 1 (2022)
Maciej Bara, Agata Janczak, Toxicity of anesthetic gases: exposure in operating rooms and influence on the environment. , Prospects in Pharmaceutical Sciences: Tom 21 Nr 3 (2023)
Małgorzata Krzyżanowska, Katarzyna Kozon, Jakub Olszewski, Andrzej Patyra, Efficacy of satralizumab therapy in the treatment of NMOSD , Prospects in Pharmaceutical Sciences: Tom 21 Nr 3 (2023)

Szczegóły

Bibliografia

Statystyki

Autorzy

Pobierz pliki

PDF (English)

Zasady cytowania

Piasecki, A., Sitnik, M., Olszewski, J., Bara, M., Herjan, K., & Armański, P. (2024). The changing landscape of mineralocorticoid receptor antagonists – finerenone in cardiovascular and renal health. Prospects in Pharmaceutical Sciences, 22(1), 11–15. https://doi.org/10.56782/pps.181

Wskaźniki altmetryczne

Cited by / Share

Licencja

Utwór dostępny jest na licencji Creative Commons Uznanie autorstwa 4.0 Międzynarodowe.

Bibliografia

Kolkhof, P.; Barfacker, L. 30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor antagonists: 60 years of research and development. J. Endocrinol. 2017, 234 (1), T125-T140. DOI: 10.1530/JOE-16-0600 DOI: https://doi.org/10.1530/JOE-16-0600

Funder, J. W. Mineralocorticoid receptor antagonists: emerging roles in cardiovascular medicine. Integr. Blood Press. Control 2013, 6, 129-138. DOI: 10.2147/IBPC.S13783 DOI: https://doi.org/10.2147/IBPC.S13783

Williams, B.; Mancia, G.; et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur. Heart J. 2018, 39 (33), 3021-3104. DOI: 10.1093/eurheartj/ehy339 DOI: https://doi.org/10.1093/eurheartj/ehy439

PubChem Compound Summary for CID 5833, Spironolactone. National Center for Biotechnology Information. https://pubchem.ncbi.nlm.nih.gov/compound/Spironolactone (accessed 2023 December 5th).

Delyani, J. A. Mineralocorticoid receptor antagonists: the evolution of utility and pharmacology. Kidney Int. 2000, 57 (4), 1408-1411. DOI: 10.1046/j.1523-1755.2000.00983.x DOI: https://doi.org/10.1046/j.1523-1755.2000.00983.x

Craft, J. Eplerenone (Inspra), a new aldosterone antagonist for the treatment of systemic hypertension and heart failure. Proc. (Bayl. Univ. Med. Cent.) 2004, 17 (2), 217-220. DOI: 10.1080/08998280.2004.11927973 DOI: https://doi.org/10.1080/08998280.2004.11927973

McDonagh, T. A.; Metra, M.; et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. 2021, 42 (36), 3599-3726. DOI: 10.1093/eurheartj/ehab368 DOI: https://doi.org/10.1093/eurheartj/ehab368

Delyani, J. A.; Rocha, R.; et al. Eplerenone: a selective aldosterone receptor antagonist (SARA). Cardiovasc. Drug Rev. 2001, 19 (3), 185-200. DOI: 10.1111/j.1527-3466.2001.tb00064.x DOI: https://doi.org/10.1111/j.1527-3466.2001.tb00064.x

Kolkhof, P.; Joseph, A.; et al. Nonsteroidal mineralocorticoid receptor antagonism for cardiovascular and renal disorders - New perspectives for combination therapy. Pharmacol. Res. 2021, 172, 105859. DOI: 10.1016/j.phrs.2021.105859 DOI: https://doi.org/10.1016/j.phrs.2021.105859

Georgianos, P. I.; Agarwal, R. Mineralocorticoid Receptor Antagonism in Chronic Kidney Disease. Kidney Int. Rep. 2021, 6 (9), 2281-2291. DOI: 10.1016/j.ekir.2021.05.027 DOI: https://doi.org/10.1016/j.ekir.2021.05.027

Agarwal, R.; Anker, S. D.; et al. Investigating new treatment opportunities for patients with chronic kidney disease in type 2 diabetes: the role of finerenone. Nephrol. Dial. Transplant. 2022, 37 (6), 1014-1023. DOI: 10.1093/ndt/gfaa294 DOI: https://doi.org/10.1093/ndt/gfaa294

Buonafine, M.; Bonnard, B.; et al. Mineralocorticoid Receptor and Cardiovascular Disease. Am. J. Hypertens. 2018, 31 (11), 1165-1174. DOI: 10.1093/ajh/hpy120 DOI: https://doi.org/10.1093/ajh/hpy120

Currie, G.; Taylor, A. H.; 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), Art. No: 127. DOI: 10.1186/s12882-016-0337-0 DOI: https://doi.org/10.1186/s12882-016-0337-0

Kerendia: EPAR - Product Information. https://www.ema.europa.eu/en/documents/product-information/kerendia-epar-product-information_en.pdf (accessed 2023 December 7th).

Kintscher, U.; Bakris, G. L.; et al. Novel non-steroidal mineralocorticoid receptor antagonists in cardiorenal disease. Br. J. Pharmacol. 2022, 179 (13), 3220-3234. DOI: 10.1111/bph.15747 DOI: https://doi.org/10.1111/bph.15747

Kolkhof, P.; Lawatscheck, R.; et al. Nonsteroidal Mineralocorticoid Receptor Antagonism by Finerenone-Translational Aspects and Clinical Perspectives across Multiple Organ Systems. Int. J. Mol. Sci. 2022, 23 (16), Art. No: 9243, DOI: 10.3390/ijms23169243 DOI: https://doi.org/10.3390/ijms23169243

Bauersachs, J.; Jaisser, F.; et al. Mineralocorticoid receptor activation and mineralocorticoid receptor antagonist treatment in cardiac and renal diseases. Hypertension 2015, 65 (2), 257-263. DOI: 10.1161/HYPERTENSIONAHA.114.04488 DOI: https://doi.org/10.1161/HYPERTENSIONAHA.114.04488

Berger, S.; Bleich, M.; et al. Mineralocorticoid receptor knockout mice: lessons on Na+ metabolism. Kidney Int. 2000, 57 (4), 1295-1298. DOI: 10.1046/j.1523-1755.2000.00965.x DOI: https://doi.org/10.1046/j.1523-1755.2000.00965.x

Barrera-Chimal, J.; Jaisser, F. Pathophysiologic mechanisms in diabetic kidney disease: A focus on current and future therapeutic targets. Diabetes Obes. Metab. 2020, 22 Suppl 1, 16-31. DOI: 10.1111/dom.13969 DOI: https://doi.org/10.1111/dom.13969

Barrera-Chimal, J.; Girerd, S.; et al. Mineralocorticoid receptor antagonists and kidney diseases: pathophysiological basis. Kidney Int. 2019, 96 (2), 302-319. DOI: 10.1016/j.kint.2019.02.030 DOI: https://doi.org/10.1016/j.kint.2019.02.030

Barrera-Chimal, J.; Estrela, G. R.; et al. The myeloid mineralocorticoid receptor controls inflammatory and fibrotic responses after renal injury via macrophage interleukin-4 receptor signaling. Kidney Int. 2018, 93 (6), 1344-1355. DOI: 10.1016/j.kint.2017.12.016 DOI: https://doi.org/10.1016/j.kint.2017.12.016

Bauersachs, J.; Lopez-Andres, N. Mineralocorticoid receptor in cardiovascular diseases-Clinical trials and mechanistic insights. Br. J. Pharmacol. 2022, 179 (13), 3119-3134. DOI: 10.1111/bph.15708 DOI: https://doi.org/10.1111/bph.15708

Lother, A.; Berger, S.; et al. Ablation of mineralocorticoid receptors in myocytes but not in fibroblasts preserves cardiac function. Hypertension 2011, 57 (4), 746-754. DOI: 10.1161/HYPERTENSIONAHA.110.163287 DOI: https://doi.org/10.1161/HYPERTENSIONAHA.110.163287

Rickard, A. J.; Morgan, J.; et al. Endothelial cell mineralocorticoid receptors regulate deoxycorticosterone/salt-mediated cardiac remodeling and vascular reactivity but not blood pressure. Hypertension 2014, 63 (5), 1033-1040. DOI: 10.1161/HYPERTENSIONAHA.113.01803 DOI: https://doi.org/10.1161/HYPERTENSIONAHA.113.01803

Rickard, A. J.; Morgan, J.; et al. Cardiomyocyte mineralocorticoid receptors are essential for deoxycorticosterone/salt-mediated inflammation and cardiac fibrosis. Hypertension 2012, 60 (6), 1443-1450. DOI: 10.1161/HYPERTENSIONAHA.112.203158 DOI: https://doi.org/10.1161/HYPERTENSIONAHA.112.203158

Pitt, B.; Zannad, F.; 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), 709-717. DOI: 10.1056/NEJM199909023411001 DOI: https://doi.org/10.1056/NEJM199909023411001

Zannad, F.; McMurray, J. J.; et al. Eplerenone in patients with systolic heart failure and mild symptoms. N. Engl. J. Med. 2011, 364 (1), 11-21. DOI: 10.1056/NEJMoa1009492 DOI: https://doi.org/10.1056/NEJMoa1009492

Pitt, B.; Remme, W.; et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N. Engl. J. Med. 2003, 348 (14), 1309-1321. DOI: 10.1056/NEJMoa030207 DOI: https://doi.org/10.1056/NEJMoa030207

Pitt, B.; Pfeffer, M. A.; et al. Spironolactone for heart failure with preserved ejection fraction. N. Engl. J. Med. 2014, 370 (15), 1383-1392. DOI: 10.1056/NEJMoa1313731 DOI: https://doi.org/10.1056/NEJMoa1313731

Bianchi, S.; Bigazzi, R.; et al. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int, 2006, 70 (12), 2116-2123. DOI: 10.1038/sj.ki.5001854 DOI: https://doi.org/10.1038/sj.ki.5001854

Tsuboi, N.; Kawamura, T.; et al. 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), 113-117. DOI: 10.1177/1470320311412811 DOI: https://doi.org/10.1177/1470320311412811

Epstein, M.; Williams, G. H.; et al. Selective aldosterone blockade with eplerenone reduces albuminuria in patients with type 2 diabetes. Clin. J. Am. Soc. Nephrol. 2006, 1 (5), 940-951. DOI: 10.2215/CJN.00240106 DOI: https://doi.org/10.2215/CJN.00240106

Amazit, L.; Le Billan, F.; et al. Finerenone Impedes Aldosterone-dependent Nuclear Import of the Mineralocorticoid Receptor and Prevents Genomic Recruitment of Steroid Receptor Coactivator-1. J. Biol. Chem. 2015, 290 (36), 21876-21889. DOI: 10.1074/jbc.M115.657957 DOI: https://doi.org/10.1074/jbc.M115.657957

Kintscher, U.; Edelmann, F. The non-steroidal mineralocorticoid receptor antagonist finerenone and heart failure with preserved ejection fraction. Cardiovasc. Diabetol. 2023, 22 (1), Art. No: 162. DOI: 10.1186/s12933-023-01899-0 DOI: https://doi.org/10.1186/s12933-023-01899-0

Agarwal, R.; Kolkhof, P.; et al. Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine. Eur. Heart J. 2021, 42 (2), 152-161. DOI: 10.1093/eurheartj/ehaa736 DOI: https://doi.org/10.1093/eurheartj/ehaa736

Heinig, R.; Kimmeskamp-Kirschbaum, N.; et al. 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. DOI: 10.1002/cpdd.263 DOI: https://doi.org/10.1002/cpdd.263

Kolkhof, P.; Delbeck, M.; et al. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. J. Cardiovasc. Pharmacol. 2014, 64 (1), 69-78. DOI: 10.1097/FJC.0000000000000091 DOI: https://doi.org/10.1097/FJC.0000000000000091

Rico-Mesa, J. S.; White, A.; et al. Mineralocorticoid Receptor Antagonists: a Comprehensive Review of Finerenone. Curr. Cardiol. Rep. 2020, 22 (11), Art. No: 140. DOI: 10.1007/s11886-020-01399-7 DOI: https://doi.org/10.1007/s11886-020-01399-7

Pitt, B.; Kober, L.; 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), 2453-2463. DOI: 10.1093/eurheartj/eht187 DOI: https://doi.org/10.1093/eurheartj/eht187

Filippatos, G.; Anker, S. D.; 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), 2105-2114. DOI: 10.1093/eurheartj/ehw132 DOI: https://doi.org/10.1093/eurheartj/ehw132

Bakris, G. L.; Agarwal, R.; et al. Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial. JAMA 2015, 314 (9), 884-894. DOI: 10.1001/jama.2015.10081 DOI: https://doi.org/10.1001/jama.2015.10081

Bakris, G. L.; Agarwal, R.; et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N. Engl. J. Med. 2020, 383 (23), 2219-2229. DOI: 10.1056/NEJMoa2025845 DOI: https://doi.org/10.1056/NEJMoa2025845

Filippatos, G.; Anker, S. D.; et al. Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes. Circulation 2021, 143 (6), 540-552. DOI: 10.1161/CIRCULATIONAHA.120.051898 DOI: https://doi.org/10.1161/CIRCULATIONAHA.120.051898

Pitt, B.; Filippatos, G.; et al. Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes. N. Engl. J. Med. 2021, 385 (24), 2252-2263. DOI: 10.1056/NEJMoa2110956 DOI: https://doi.org/10.1056/NEJMoa2110956

Filippatos, G.; Anker, S. D.; et al. Finerenone Reduces Risk of Incident Heart Failure in Patients With Chronic Kidney Disease and Type 2 Diabetes: Analyses From the FIGARO-DKD Trial. Circulation 2022, 145 (6), 437-447. DOI: 10.1161/CIRCULATIONAHA.121.057983 DOI: https://doi.org/10.1161/CIRCULATIONAHA.121.057983

Filippatos, G.; Pitt, B.; et al. Finerenone in patients with chronic kidney disease and type 2 diabetes with and without heart failure: a prespecified subgroup analysis of the FIDELIO-DKD trial. Eur. J. Heart. Fail. 2022, 24 (6), 996-1005. DOI: 10.1002/ejhf.2469 DOI: https://doi.org/10.1002/ejhf.2469

Agarwal, R.; Filippatos, G.; et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur. Heart J. 2022, 43 (6), 474-484. DOI: 10.1093/eurheartj/ehab777 DOI: https://doi.org/10.1093/eurheartj/ehab886

Adam Piasecki

adam.piasecki1@wum.edu.pl
https://orcid.org/0009-0002-5614-6415

Afiliacja:

a:1:{s:5:"en_US";s:45:"Doctoral School, Medical University of Warsaw";} Poland

Magdalena Sitnik

Afiliacja:

Masovian Brodnowski Hospital, 03-242 Warsaw, Poland Poland

Jakub Olszewski

Afiliacja:

Masovian Brodnowski Hospital, 03-242 Warsaw, Poland Poland

Maciej Bara

Afiliacja:

Infant Jesus Clinical Hospital, Medical University of Warsaw, 02-005 Warsaw, Poland Poland

Katarzyna Herjan

Afiliacja:

Center of Postgraduate Medical Education, Prof. W. Orłowski Memorial Hospital, 00-401 Warsaw, Poland Poland

Piotr Armański

Afiliacja:

District Hospital in Sochaczew, 96-500 Sochaczew, Poland Poland