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

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 angiot...

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Autores principales: Palanisamy, Srikanth, Funes Hernandez, Mario, Chang, Tara I., Mahaffey, Kenneth W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381668/
https://www.ncbi.nlm.nih.gov/pubmed/35737275
http://dx.doi.org/10.1007/s40119-022-00269-3
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author Palanisamy, Srikanth
Funes Hernandez, Mario
Chang, Tara I.
Mahaffey, Kenneth W.
author_facet Palanisamy, Srikanth
Funes Hernandez, Mario
Chang, Tara I.
Mahaffey, Kenneth W.
author_sort Palanisamy, Srikanth
collection PubMed
description 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.
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spelling pubmed-93816682022-08-18 Cardiovascular and Renal Outcomes with Finerenone, a Selective Mineralocorticoid Receptor Antagonist Palanisamy, Srikanth Funes Hernandez, Mario Chang, Tara I. Mahaffey, Kenneth W. Cardiol Ther Review 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. Springer Healthcare 2022-06-23 2022-09 /pmc/articles/PMC9381668/ /pubmed/35737275 http://dx.doi.org/10.1007/s40119-022-00269-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Review
Palanisamy, Srikanth
Funes Hernandez, Mario
Chang, Tara I.
Mahaffey, Kenneth W.
Cardiovascular and Renal Outcomes with Finerenone, a Selective Mineralocorticoid Receptor Antagonist
title Cardiovascular and Renal Outcomes with Finerenone, a Selective Mineralocorticoid Receptor Antagonist
title_full Cardiovascular and Renal Outcomes with Finerenone, a Selective Mineralocorticoid Receptor Antagonist
title_fullStr Cardiovascular and Renal Outcomes with Finerenone, a Selective Mineralocorticoid Receptor Antagonist
title_full_unstemmed Cardiovascular and Renal Outcomes with Finerenone, a Selective Mineralocorticoid Receptor Antagonist
title_short Cardiovascular and Renal Outcomes with Finerenone, a Selective Mineralocorticoid Receptor Antagonist
title_sort cardiovascular and renal outcomes with finerenone, a selective mineralocorticoid receptor antagonist
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381668/
https://www.ncbi.nlm.nih.gov/pubmed/35737275
http://dx.doi.org/10.1007/s40119-022-00269-3
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