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Aldosterone receptor antagonists: biology and novel therapeutic applications
1Istituto di Endocrinologia, University of Milan, via G. Balzaretti, 9, 20133 Milano, Italy. paolo.magni@unimi.it
Insights
Aldosterone antagonists (ARAs) combat cardiovascular diseases by preventing heart remodeling and fibrosis. Clinical trials demonstrate ARAs improve survival and reduce cardiac issues when added to standard treatments.
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Pharmacology
Background:
- Aldosterone system dysregulation contributes to cardiovascular diseases like heart failure and hypertension.
- Aldosterone promotes myocardial remodeling and fibrosis in humans and animal models.
- Aldosterone antagonists (ARAs) are established treatments for aldosterone excess syndromes.
Purpose of the Study:
- To evaluate the efficacy of aldosterone antagonists (ARAs) in managing cardiovascular diseases.
- To highlight the benefits of selective mineralocorticoid receptor antagonists like eplerenone.
- To support the use of ARAs as adjunct therapy for heart failure and hypertension.
Main Methods:
- Review of clinical trials, including the Randomized Aldactone Evaluation Study (RALES) and Eplerenone Neurohormonal Efficacy and Survival Study (EPHESUS).
- Analysis of aldosterone's role in cardiovascular pathophysiology.
- Assessment of spironolactone-class and selective ARAs.
Main Results:
- Aldosterone antagonists (ARAs) demonstrate significant benefits in treating myocardial failure and selected hypertension cases.
- Trials like RALES and EPHESUS provide strong evidence for ARA efficacy.
- Selective ARAs, such as eplerenone, offer potential for reduced endocrine side effects.
Conclusions:
- Adding aldosterone antagonists (ARAs) to conventional therapy improves survival rates in cardiovascular patients.
- ARAs reduce the incidence of cardiac complications in conditions like heart failure.
- Targeting the aldosterone system with ARAs is a valuable therapeutic strategy for cardiovascular disease management.
Abstract:
A dysregulation of the aldosterone system has been involved in the pathophysiology of cardiovascular diseases, including myocardial failure and, partially, essential hypertension. In humans and in rat models, aldosterone action induces heart remodeling and interstitial and perivascular myocardial fibrosis. Therefore, a rationale for using aldosterone antagonists (ARAs) of the spironolactone family, which have been available for decades for the treatment of aldosterone excess syndromes, has now emerged. The development of compounds such as eplerenone, with a greater selectivity for mineralocorticoid receptors, is promising also in terms of reduction of endocrine side effects. The use of ARAs for the treatment of myocardial failure and selected cases of hypertension, in combination with the current therapy, has been strongly supported by trials such as the Randomized Aldactone Evaluation Study (RALES) and the Eplerenone Neurohormonal Efficacy and Survival Study (EPHESUS). Thus, the addition of ARAs to the conventional therapy appears beneficial, leading to an improved survival rate and a reduced incidence of cardiac complications.
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