Evidence for Aldosterone Antagonism in Heart Failure

Activation of the renin–angiotensin–aldosterone system is the ultimate pathophysiological hallmark in heart failure. Though aldosterone primarily appears to regulate electrolyte homeostasis by acting on distal nephrons in the kidneys, its effects are far-reaching across the cardiovascular system as...

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Main Authors: Rishi Sethi, Pravesh Vishwakarma, Akshyaya Pradhan
Format: Article
Language:English
Published: Radcliffe Medical Media 2024-11-01
Series:Cardiac Failure Review
Online Access:https://www.cfrjournal.com/articleindex/cfr.2024.10
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author Rishi Sethi
Pravesh Vishwakarma
Akshyaya Pradhan
author_facet Rishi Sethi
Pravesh Vishwakarma
Akshyaya Pradhan
author_sort Rishi Sethi
collection DOAJ
description Activation of the renin–angiotensin–aldosterone system is the ultimate pathophysiological hallmark in heart failure. Though aldosterone primarily appears to regulate electrolyte homeostasis by acting on distal nephrons in the kidneys, its effects are far-reaching across the cardiovascular system as its receptors are also expressed in vascular smooth muscle cells, endothelial cells, macrophages and cardiomyocytes. Aldosterone excess leads to vascular stiffness, vasoconstriction, endothelial dysfunction, inflammation, oxidative stress, cardiac fibrosis and hypertrophy, atherogenesis and thrombosis. Hence, aldosterone antagonism is an attractive proposition for heart failure management. The first-generation non-selective mineralocorticoid receptor antagonist spironolactone produced a spectacular reduction of cardiovascular outcomes in the seminal RALES study, while the selective second-generation congener eplerenone boasts two positive studies: EPHESUS and EMPHASIS-HF. The TOPCAT trial indicated that a specific subgroup of patients with heart failure with preserved ejection fraction may benefit from targeted therapy of mineralocorticoid receptor antagonists. Newer-generation non-steroidal mineralocorticoid antagonists and aldosterone synthase inhibitors are being evaluated in randomised trials.
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series Cardiac Failure Review
spelling doaj-art-a2e2f59516ff48a880b8cb083e6214a42024-12-14T16:05:24ZengRadcliffe Medical MediaCardiac Failure Review2057-75402057-75592024-11-011010.15420/cfr.2024.10Evidence for Aldosterone Antagonism in Heart FailureRishi Sethi0Pravesh Vishwakarma1Akshyaya Pradhan2Department of Cardiology, King George’s Medical University, Uttar Pradesh, IndiaDepartment of Cardiology, King George’s Medical University, Uttar Pradesh, IndiaDepartment of Cardiology, King George’s Medical University, Uttar Pradesh, IndiaActivation of the renin–angiotensin–aldosterone system is the ultimate pathophysiological hallmark in heart failure. Though aldosterone primarily appears to regulate electrolyte homeostasis by acting on distal nephrons in the kidneys, its effects are far-reaching across the cardiovascular system as its receptors are also expressed in vascular smooth muscle cells, endothelial cells, macrophages and cardiomyocytes. Aldosterone excess leads to vascular stiffness, vasoconstriction, endothelial dysfunction, inflammation, oxidative stress, cardiac fibrosis and hypertrophy, atherogenesis and thrombosis. Hence, aldosterone antagonism is an attractive proposition for heart failure management. The first-generation non-selective mineralocorticoid receptor antagonist spironolactone produced a spectacular reduction of cardiovascular outcomes in the seminal RALES study, while the selective second-generation congener eplerenone boasts two positive studies: EPHESUS and EMPHASIS-HF. The TOPCAT trial indicated that a specific subgroup of patients with heart failure with preserved ejection fraction may benefit from targeted therapy of mineralocorticoid receptor antagonists. Newer-generation non-steroidal mineralocorticoid antagonists and aldosterone synthase inhibitors are being evaluated in randomised trials.https://www.cfrjournal.com/articleindex/cfr.2024.10
spellingShingle Rishi Sethi
Pravesh Vishwakarma
Akshyaya Pradhan
Evidence for Aldosterone Antagonism in Heart Failure
Cardiac Failure Review
title Evidence for Aldosterone Antagonism in Heart Failure
title_full Evidence for Aldosterone Antagonism in Heart Failure
title_fullStr Evidence for Aldosterone Antagonism in Heart Failure
title_full_unstemmed Evidence for Aldosterone Antagonism in Heart Failure
title_short Evidence for Aldosterone Antagonism in Heart Failure
title_sort evidence for aldosterone antagonism in heart failure
url https://www.cfrjournal.com/articleindex/cfr.2024.10
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