Skip to main content
Top
Published in: Cardiology and Therapy 3/2022

Open Access 23-06-2022 | Spironolactone | Review

Cardiovascular and Renal Outcomes with Finerenone, a Selective Mineralocorticoid Receptor Antagonist

Authors: Srikanth Palanisamy, Mario Funes Hernandez, Tara I. Chang, Kenneth W. Mahaffey

Published in: Cardiology and Therapy | Issue 3/2022

Login to get access

Abstract

Overactivation of the renin–angiotensin–aldosterone system (RAAS) has been shown to be pathologic in heart failure and albuminuric chronic kidney disease (CKD), triggering pro-inflammatory and pro-fibrotic cellular pathways. The standard of care in these disease states includes treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers. Mineralocorticoid receptor antagonists (MRAs) are also a mainstay in the treatment of heart failure with reduced ejection fraction; however, therapy is often limited by treatment-related hyperkalemia. In albuminuric CKD, the risk of hyperkalemia, acute kidney injury (AKI), and hypotension also remains significant. Finerenone is a novel non-steroidal MRA that may obviate some of these concerns and have therapeutic potential in additional patient populations. Finerenone was developed using the chemical structure of a dihydropyridine channel blocker but optimized to create a bulky MRA without any activity at the L-type calcium channel. It has several novel cellular mechanisms that may account for its ability to reduce cardiac hypertrophy and proteinuria more efficiently than an equinatriuretic dose of a steroidal MRA, while retaining anti-inflammatory and anti-fibrotic properties. Finerenone also has a lower rate of treatment-related hyperkalemia and AKI than steroidal MRAs with a smaller effect on systolic blood pressure, greatly expanding its therapeutic utility. The recently published FIGARO-DKD and FIDELIO-DKD trials demonstrate that treatment with finerenone in patients with type II diabetes and albuminuric CKD results in improved cardiovascular outcomes and a lower risk of CKD progression. Patients enrolled in these studies were already on maximally tolerated ACE inhibitor or angiotensin receptor blocker therapy. Trials investigating finerenone’s therapeutic effect in patients with heart failure with preserved ejection fraction (HFpEF) and non-diabetic CKD, as well sodium–glucose cotransporter 2 (SGLT2) and finerenone combination therapy in patients with diabetic nephropathy, are ongoing.
Literature
1.
go back to reference Kolkhof P, Barfacker L. 30 years of the mineralocorticoid receptor: mineralocorticoid receptor antagonists: 60 years of research and development. J Endocrinol. 2017;234(1):T125–40.PubMedPubMedCentralCrossRef Kolkhof P, Barfacker L. 30 years of the mineralocorticoid receptor: mineralocorticoid receptor antagonists: 60 years of research and development. J Endocrinol. 2017;234(1):T125–40.PubMedPubMedCentralCrossRef
3.
go back to reference Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128(16):1810–52.PubMedCrossRef Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128(16):1810–52.PubMedCrossRef
4.
go back to reference Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Card Fail. 2017;23(8):628–51.PubMedCrossRef Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Card Fail. 2017;23(8):628–51.PubMedCrossRef
5.
go back to reference Bolignano D, Palmer SC, Navaneethan SD, Strippoli GF. Aldosterone antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2014;4:CD007004. Bolignano D, Palmer SC, Navaneethan SD, Strippoli GF. Aldosterone antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2014;4:CD007004.
6.
go back to reference Currie G, Taylor AH, Fujita T, 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.PubMedPubMedCentralCrossRef Currie G, Taylor AH, Fujita T, 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.PubMedPubMedCentralCrossRef
7.
go back to reference Kidney Disease: Improving Global Outcomes Blood Pressure Work Group. KDIGO 2021 clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int. 2021;99(3S):S1–87. Kidney Disease: Improving Global Outcomes Blood Pressure Work Group. KDIGO 2021 clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int. 2021;99(3S):S1–87.
8.
go back to reference Kolkhof P, Delbeck M, Kretschmer A, et al. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. J Cardiovasc Pharmacol. 2014;64(1):69–78.PubMedCrossRef Kolkhof P, Delbeck M, Kretschmer A, et al. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. J Cardiovasc Pharmacol. 2014;64(1):69–78.PubMedCrossRef
9.
go back to reference Pitt B, Kober L, Ponikowski P, 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.PubMedPubMedCentralCrossRef Pitt B, Kober L, Ponikowski P, 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.PubMedPubMedCentralCrossRef
10.
go back to reference Yang J, Young MJ. Mineralocorticoid receptor antagonists-pharmacodynamics and pharmacokinetic differences. Curr Opin Pharmacol. 2016;27:78–85.PubMedCrossRef Yang J, Young MJ. Mineralocorticoid receptor antagonists-pharmacodynamics and pharmacokinetic differences. Curr Opin Pharmacol. 2016;27:78–85.PubMedCrossRef
11.
go back to reference Amazit L, Le Billan F, Kolkhof P, 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):21876–89.PubMedPubMedCentralCrossRef Amazit L, Le Billan F, Kolkhof P, 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):21876–89.PubMedPubMedCentralCrossRef
12.
go back to reference Fagart J, Hillisch A, Huyet J, et al. A new mode of mineralocorticoid receptor antagonism by a potent and selective nonsteroidal molecule. J Biol Chem. 2010;285(39):29932–40.PubMedPubMedCentralCrossRef Fagart J, Hillisch A, Huyet J, et al. A new mode of mineralocorticoid receptor antagonism by a potent and selective nonsteroidal molecule. J Biol Chem. 2010;285(39):29932–40.PubMedPubMedCentralCrossRef
13.
go back to reference Fagart J, Wurtz JM, Souque A, Hellal-Levy C, Moras D, Rafestin-Oblin ME. Antagonism in the human mineralocorticoid receptor. EMBO J. 1998;17(12):3317–25.PubMedPubMedCentralCrossRef Fagart J, Wurtz JM, Souque A, Hellal-Levy C, Moras D, Rafestin-Oblin ME. Antagonism in the human mineralocorticoid receptor. EMBO J. 1998;17(12):3317–25.PubMedPubMedCentralCrossRef
14.
go back to reference Tomaschitz A, Pilz S, Ritz E, Meinitzer A, Boehm BO, Marz W. Plasma aldosterone levels are associated with increased cardiovascular mortality: the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Eur Heart J. 2010;31(10):1237–47.PubMedCrossRef Tomaschitz A, Pilz S, Ritz E, Meinitzer A, Boehm BO, Marz W. Plasma aldosterone levels are associated with increased cardiovascular mortality: the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Eur Heart J. 2010;31(10):1237–47.PubMedCrossRef
15.
go back to reference Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005;45(8):1243–8.PubMedCrossRef Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005;45(8):1243–8.PubMedCrossRef
17.
go back to reference Keidar S, Kaplan M, Pavlotzky E, et al. Aldosterone administration to mice stimulates macrophage NADPH oxidase and increases atherosclerosis development: a possible role for angiotensin-converting enzyme and the receptors for angiotensin II and aldosterone. Circulation. 2004;109(18):2213–20.PubMedCrossRef Keidar S, Kaplan M, Pavlotzky E, et al. Aldosterone administration to mice stimulates macrophage NADPH oxidase and increases atherosclerosis development: a possible role for angiotensin-converting enzyme and the receptors for angiotensin II and aldosterone. Circulation. 2004;109(18):2213–20.PubMedCrossRef
18.
go back to reference Hirono Y, Yoshimoto T, Suzuki N, et al. Angiotensin II receptor type 1-mediated vascular oxidative stress and proinflammatory gene expression in aldosterone-induced hypertension: the possible role of local renin-angiotensin system. Endocrinology. 2007;148(4):1688–96.PubMedCrossRef Hirono Y, Yoshimoto T, Suzuki N, et al. Angiotensin II receptor type 1-mediated vascular oxidative stress and proinflammatory gene expression in aldosterone-induced hypertension: the possible role of local renin-angiotensin system. Endocrinology. 2007;148(4):1688–96.PubMedCrossRef
19.
go back to reference Johar S, Cave AC, Narayanapanicker A, Grieve DJ, Shah AM. Aldosterone mediates angiotensin II-induced interstitial cardiac fibrosis via a Nox2-containing NADPH oxidase. FASEB J. 2006;20(9):1546–8.PubMedCrossRef Johar S, Cave AC, Narayanapanicker A, Grieve DJ, Shah AM. Aldosterone mediates angiotensin II-induced interstitial cardiac fibrosis via a Nox2-containing NADPH oxidase. FASEB J. 2006;20(9):1546–8.PubMedCrossRef
20.
go back to reference Stas S, Whaley-Connell A, Habibi J, et al. Mineralocorticoid receptor blockade attenuates chronic overexpression of the renin-angiotensin-aldosterone system stimulation of reduced nicotinamide adenine dinucleotide phosphate oxidase and cardiac remodeling. Endocrinology. 2007;148(8):3773–80.PubMedCrossRef Stas S, Whaley-Connell A, Habibi J, et al. Mineralocorticoid receptor blockade attenuates chronic overexpression of the renin-angiotensin-aldosterone system stimulation of reduced nicotinamide adenine dinucleotide phosphate oxidase and cardiac remodeling. Endocrinology. 2007;148(8):3773–80.PubMedCrossRef
21.
go back to reference Bauersachs J, Heck M, Fraccarollo D, et al. Addition of spironolactone to angiotensin-converting enzyme inhibition in heart failure improves endothelial vasomotor dysfunction: role of vascular superoxide anion formation and endothelial nitric oxide synthase expression. J Am Coll Cardiol. 2002;39(2):351–8.PubMedCrossRef Bauersachs J, Heck M, Fraccarollo D, et al. Addition of spironolactone to angiotensin-converting enzyme inhibition in heart failure improves endothelial vasomotor dysfunction: role of vascular superoxide anion formation and endothelial nitric oxide synthase expression. J Am Coll Cardiol. 2002;39(2):351–8.PubMedCrossRef
22.
go back to reference Nagata D, Takahashi M, Sawai K, et al. Molecular mechanism of the inhibitory effect of aldosterone on endothelial NO synthase activity. Hypertension. 2006;48(1):165–71.PubMedCrossRef Nagata D, Takahashi M, Sawai K, et al. Molecular mechanism of the inhibitory effect of aldosterone on endothelial NO synthase activity. Hypertension. 2006;48(1):165–71.PubMedCrossRef
23.
go back to reference Leopold JA, Dam A, Maron BA, et al. Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity. Nat Med. 2007;13(2):189–97.PubMedPubMedCentralCrossRef Leopold JA, Dam A, Maron BA, et al. Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity. Nat Med. 2007;13(2):189–97.PubMedPubMedCentralCrossRef
24.
go back to reference Brilla CG, Weber KT. Mineralocorticoid excess, dietary sodium, and myocardial fibrosis. J Lab Clin Med. 1992;120(6):893–901.PubMed Brilla CG, Weber KT. Mineralocorticoid excess, dietary sodium, and myocardial fibrosis. J Lab Clin Med. 1992;120(6):893–901.PubMed
25.
go back to reference Selye H. Protection by a steroid-spirolactone against certain types of cardiac necroses. Proc Soc Exp Biol Med. 1960;104:212–3.PubMedCrossRef Selye H. Protection by a steroid-spirolactone against certain types of cardiac necroses. Proc Soc Exp Biol Med. 1960;104:212–3.PubMedCrossRef
26.
go back to reference Young M, Funder JW. Eplerenone, but not steroid withdrawal, reverses cardiac fibrosis in deoxycorticosterone/salt-treated rats. Endocrinology. 2004;145(7):3153–7.PubMedCrossRef Young M, Funder JW. Eplerenone, but not steroid withdrawal, reverses cardiac fibrosis in deoxycorticosterone/salt-treated rats. Endocrinology. 2004;145(7):3153–7.PubMedCrossRef
27.
go back to reference Suzuki G, Morita H, Mishima T, et al. Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure. Circulation. 2002;106(23):2967–72.PubMedCrossRef Suzuki G, Morita H, Mishima T, et al. Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure. Circulation. 2002;106(23):2967–72.PubMedCrossRef
28.
go back to reference Rocha R, Rudolph AE, Frierdich GE, et al. Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol. 2002;283(5):H1802–10.PubMedCrossRef Rocha R, Rudolph AE, Frierdich GE, et al. Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol. 2002;283(5):H1802–10.PubMedCrossRef
29.
go back to reference Lavall D, Jacobs N, Mahfoud F, Kolkhof P, Bohm M, Laufs U. The non-steroidal mineralocorticoid receptor antagonist finerenone prevents cardiac fibrotic remodeling. Biochem Pharmacol. 2019;168:173–83.PubMedCrossRef Lavall D, Jacobs N, Mahfoud F, Kolkhof P, Bohm M, Laufs U. The non-steroidal mineralocorticoid receptor antagonist finerenone prevents cardiac fibrotic remodeling. Biochem Pharmacol. 2019;168:173–83.PubMedCrossRef
30.
go back to reference Grune J, Benz V, Brix S, et al. Steroidal and nonsteroidal mineralocorticoid receptor antagonists cause differential cardiac gene expression in pressure overload-induced cardiac hypertrophy. J Cardiovasc Pharmacol. 2016;67(5):402–11.PubMedCrossRef Grune J, Benz V, Brix S, et al. Steroidal and nonsteroidal mineralocorticoid receptor antagonists cause differential cardiac gene expression in pressure overload-induced cardiac hypertrophy. J Cardiovasc Pharmacol. 2016;67(5):402–11.PubMedCrossRef
31.
go back to reference Grune J, Beyhoff N, Smeir E, et al. Selective mineralocorticoid receptor cofactor modulation as molecular basis for finerenone’s antifibrotic activity. Hypertension. 2018;71(4):599–608.PubMedCrossRef Grune J, Beyhoff N, Smeir E, et al. Selective mineralocorticoid receptor cofactor modulation as molecular basis for finerenone’s antifibrotic activity. Hypertension. 2018;71(4):599–608.PubMedCrossRef
32.
go back to reference Rossi GP, Bernini G, Desideri G, et al. Renal damage in primary aldosteronism: results of the PAPY Study. Hypertension. 2006;48(2):232–8.PubMedCrossRef Rossi GP, Bernini G, Desideri G, et al. Renal damage in primary aldosteronism: results of the PAPY Study. Hypertension. 2006;48(2):232–8.PubMedCrossRef
33.
go back to reference Sechi LA, Novello M, Lapenna R, et al. Long-term renal outcomes in patients with primary aldosteronism. JAMA. 2006;295(22):2638–45.PubMedCrossRef Sechi LA, Novello M, Lapenna R, et al. Long-term renal outcomes in patients with primary aldosteronism. JAMA. 2006;295(22):2638–45.PubMedCrossRef
34.
go back to reference Shibata S, Nagase M, Yoshida S, Kawachi H, Fujita T. Podocyte as the target for aldosterone: roles of oxidative stress and Sgk1. Hypertension. 2007;49(2):355–64.PubMedCrossRef Shibata S, Nagase M, Yoshida S, Kawachi H, Fujita T. Podocyte as the target for aldosterone: roles of oxidative stress and Sgk1. Hypertension. 2007;49(2):355–64.PubMedCrossRef
35.
go back to reference Nishiyama A, Yao L, Fan Y, et al. Involvement of aldosterone and mineralocorticoid receptors in rat mesangial cell proliferation and deformability. Hypertension. 2005;45(4):710–6.PubMedCrossRef Nishiyama A, Yao L, Fan Y, et al. Involvement of aldosterone and mineralocorticoid receptors in rat mesangial cell proliferation and deformability. Hypertension. 2005;45(4):710–6.PubMedCrossRef
36.
go back to reference Nishiyama A, Yao L, Nagai Y, et al. Possible contributions of reactive oxygen species and mitogen-activated protein kinase to renal injury in aldosterone/salt-induced hypertensive rats. Hypertension. 2004;43(4):841–8.PubMedCrossRef Nishiyama A, Yao L, Nagai Y, et al. Possible contributions of reactive oxygen species and mitogen-activated protein kinase to renal injury in aldosterone/salt-induced hypertensive rats. Hypertension. 2004;43(4):841–8.PubMedCrossRef
37.
go back to reference Whaley-Connell AT, Habibi J, Nistala R, et al. Mineralocorticoid receptor-dependent proximal tubule injury is mediated by a redox-sensitive mTOR/S6K1 pathway. Am J Nephrol. 2012;35(1):90–100.PubMedCrossRef Whaley-Connell AT, Habibi J, Nistala R, et al. Mineralocorticoid receptor-dependent proximal tubule injury is mediated by a redox-sensitive mTOR/S6K1 pathway. Am J Nephrol. 2012;35(1):90–100.PubMedCrossRef
38.
go back to reference Blasi ER, Rocha R, Rudolph AE, Blomme EA, Polly ML, McMahon EG. Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats. Kidney Int. 2003;63(5):1791–800.PubMedCrossRef Blasi ER, Rocha R, Rudolph AE, Blomme EA, Polly ML, McMahon EG. Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats. Kidney Int. 2003;63(5):1791–800.PubMedCrossRef
39.
go back to reference Dutzmann J, Musmann RJ, Haertle M, et al. The novel mineralocorticoid receptor antagonist finerenone attenuates neointima formation after vascular injury. PLoS ONE. 2017;12(9): e0184888.PubMedPubMedCentralCrossRef Dutzmann J, Musmann RJ, Haertle M, et al. The novel mineralocorticoid receptor antagonist finerenone attenuates neointima formation after vascular injury. PLoS ONE. 2017;12(9): e0184888.PubMedPubMedCentralCrossRef
40.
go back to reference Gonzalez-Blazquez R, Somoza B, Gil-Ortega M, 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.PubMedPubMedCentralCrossRef Gonzalez-Blazquez R, Somoza B, Gil-Ortega M, 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.PubMedPubMedCentralCrossRef
41.
go back to reference 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(10):709–17.PubMedCrossRef 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(10):709–17.PubMedCrossRef
42.
go back to reference Pitt B, Remme W, Zannad F, 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.PubMedCrossRef Pitt B, Remme W, Zannad F, 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.PubMedCrossRef
43.
go back to reference Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11–21.PubMedCrossRef Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11–21.PubMedCrossRef
44.
go back to reference Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383–92.PubMedCrossRef Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383–92.PubMedCrossRef
45.
go back to reference Elguindy AM. TOPCAT misses its primary endpoint: should spironolactone be abandoned in HFpEF? Glob Cardiol Sci Pract. 2013;2013(4):357–60.PubMedPubMedCentral Elguindy AM. TOPCAT misses its primary endpoint: should spironolactone be abandoned in HFpEF? Glob Cardiol Sci Pract. 2013;2013(4):357–60.PubMedPubMedCentral
46.
go back to reference Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345(12):851–60.PubMedCrossRef Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345(12):851–60.PubMedCrossRef
47.
go back to reference Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–9.PubMedCrossRef Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–9.PubMedCrossRef
48.
go back to reference Sato A, Hayashi K, Naruse M, Saruta T. Effectiveness of aldosterone blockade in patients with diabetic nephropathy. Hypertension. 2003;41(1):64–8.PubMedCrossRef Sato A, Hayashi K, Naruse M, Saruta T. Effectiveness of aldosterone blockade in patients with diabetic nephropathy. Hypertension. 2003;41(1):64–8.PubMedCrossRef
49.
go back to reference Schjoedt KJ, Andersen S, Rossing P, Tarnow L, Parving HH. Aldosterone escape during blockade of the renin-angiotensin-aldosterone system in diabetic nephropathy is associated with enhanced decline in glomerular filtration rate. Diabetologia. 2004;47(11):1936–9.PubMedCrossRef Schjoedt KJ, Andersen S, Rossing P, Tarnow L, Parving HH. Aldosterone escape during blockade of the renin-angiotensin-aldosterone system in diabetic nephropathy is associated with enhanced decline in glomerular filtration rate. Diabetologia. 2004;47(11):1936–9.PubMedCrossRef
50.
go back to reference Schjoedt KJ, Rossing K, Juhl TR, et al. Beneficial impact of spironolactone in diabetic nephropathy. Kidney Int. 2005;68(6):2829–36.PubMedCrossRef Schjoedt KJ, Rossing K, Juhl TR, et al. Beneficial impact of spironolactone in diabetic nephropathy. Kidney Int. 2005;68(6):2829–36.PubMedCrossRef
51.
go back to reference van den Meiracker AH, Baggen RG, Pauli S, et al. Spironolactone in type 2 diabetic nephropathy: effects on proteinuria, blood pressure and renal function. J Hypertens. 2006;24(11):2285–92.PubMedCrossRef van den Meiracker AH, Baggen RG, Pauli S, et al. Spironolactone in type 2 diabetic nephropathy: effects on proteinuria, blood pressure and renal function. J Hypertens. 2006;24(11):2285–92.PubMedCrossRef
52.
go back to reference Epstein M, Williams GH, Weinberger M, 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.PubMedCrossRef Epstein M, Williams GH, Weinberger M, 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.PubMedCrossRef
53.
go back to reference Brandt-Jacobsen NH, Johansen ML, Rasmussen J, et al. Effect of high-dose mineralocorticoid receptor antagonist eplerenone on urinary albumin excretion in patients with type 2 diabetes and high cardiovascular risk: data from the MIRAD trial. Diabetes Metab. 2021;47(4): 101190.PubMedCrossRef Brandt-Jacobsen NH, Johansen ML, Rasmussen J, et al. Effect of high-dose mineralocorticoid receptor antagonist eplerenone on urinary albumin excretion in patients with type 2 diabetes and high cardiovascular risk: data from the MIRAD trial. Diabetes Metab. 2021;47(4): 101190.PubMedCrossRef
54.
go back to reference Bakris GL, Agarwal R, Chan JC, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA. 2015;314(9):884–94.PubMedCrossRef Bakris GL, Agarwal R, Chan JC, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA. 2015;314(9):884–94.PubMedCrossRef
55.
go back to reference Filippatos G, Anker SD, Bohm M, 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.PubMedPubMedCentralCrossRef Filippatos G, Anker SD, Bohm M, 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.PubMedPubMedCentralCrossRef
56.
go back to reference Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;385(24):2252–63.PubMedCrossRef Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;385(24):2252–63.PubMedCrossRef
57.
go back to reference Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383(23):2219–29.PubMedCrossRef Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383(23):2219–29.PubMedCrossRef
58.
go back to reference Agarwal R, Filippatos G, Pitt B, 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):474–84.PubMedCrossRef Agarwal R, Filippatos G, Pitt B, 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):474–84.PubMedCrossRef
59.
go back to reference Food and Drug Administration. FDA approves drug to reduce risk of serious kidney and heart complications in adults with chronic kidney disease associated with type 2 diabetes [press release]. Food and Drug Adminstration, 2021. Food and Drug Administration. FDA approves drug to reduce risk of serious kidney and heart complications in adults with chronic kidney disease associated with type 2 diabetes [press release]. Food and Drug Adminstration, 2021.
61.
go back to reference Gay A. Letter to the Editor relative to Clin Chem Lab Med 2018;56(3):360–372. Clin Chem Lab Med. 2018;56(11):251–2.PubMedCrossRef Gay A. Letter to the Editor relative to Clin Chem Lab Med 2018;56(3):360–372. Clin Chem Lab Med. 2018;56(11):251–2.PubMedCrossRef
62.
go back to reference Solomon SD, McMurray JJV, PARAGON-HF Steering Committee and Investigators. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. Reply. N Engl J Med. 2020;382(12):1182–3.PubMed Solomon SD, McMurray JJV, PARAGON-HF Steering Committee and Investigators. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. Reply. N Engl J Med. 2020;382(12):1182–3.PubMed
63.
go back to reference Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451–61.PubMedCrossRef Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451–61.PubMedCrossRef
Metadata
Title
Cardiovascular and Renal Outcomes with Finerenone, a Selective Mineralocorticoid Receptor Antagonist
Authors
Srikanth Palanisamy
Mario Funes Hernandez
Tara I. Chang
Kenneth W. Mahaffey
Publication date
23-06-2022
Publisher
Springer Healthcare
Published in
Cardiology and Therapy / Issue 3/2022
Print ISSN: 2193-8261
Electronic ISSN: 2193-6544
DOI
https://doi.org/10.1007/s40119-022-00269-3

Other articles of this Issue 3/2022

Cardiology and Therapy 3/2022 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine