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Aldosterone blockade in heart failure
1Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK. a.d.struthers@dundee.ac.uk
Insights
Aldosterone blockade, using drugs like spironolactone and eplerenone, significantly reduces mortality risk in heart failure patients. These aldosterone antagonists are crucial for managing severe heart failure and post-myocardial infarction complications.
Area of Science:
- Cardiology
- Pharmacology
- Internal Medicine
Background:
- Aldosterone significantly contributes to heart failure pathophysiology.
- Standard treatments like ACE inhibitors may not fully suppress aldosterone.
- Unchecked aldosterone promotes adverse cardiac remodeling and dysfunction.
Purpose of the Study:
- To evaluate the efficacy of aldosterone blockade in heart failure.
- To assess the impact of spironolactone and eplerenone on patient outcomes.
Main Methods:
- The Randomized Aldactone Evaluation Study (RALES) compared spironolactone to placebo in severe heart failure.
- The Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) compared eplerenone to placebo in post-MI patients with LV dysfunction.
Main Results:
- Spironolactone reduced all-cause mortality by 30% and cardiac mortality by 31% in RALES.
- Eplerenone reduced all-cause mortality by 15% and cardiovascular events by 13% in EPHESUS.
- Both studies showed significant reductions in cardiac and sudden death risks.
Conclusions:
- Aldosterone blockade is a vital component of optimal heart failure therapy.
- Spironolactone and eplerenone offer significant survival benefits.
- Targeting aldosterone pathways improves outcomes in heart failure and post-MI patients.
Abstract:
Aldosterone plays a key role in the pathophysiology of heart failure. Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers may not suppress aldosterone production in the long term. This allows aldosterone to exert its effects on myocardial fibrosis and cardiac remodelling, endothelial function, electrolytes and baroreceptor response. The Randomized Aldactone Evaluation Study (RALES) tested spironolactone against placebo in patients with severe heart failure. The study found a 30% reduction in the risk of death among patients treated with spironolactone and a 31% reduction in the risk of death from cardiac causes. Patients in the spironolactone group had significantly lower risks of death from progression of heart failure and sudden cardiac death. The Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) investigated the effects of eplerenone against placebo in patients with myocardial infarction complicated by left ventricular dysfunction. Compared to placebo, the relative risk of death from any cause was 0.85 in eplerenone-treated patients, and the relative risk of death or hospitalisation for cardiovascular events was 0.87. The reduction in the risk of sudden death from cardiac causes was statistically significant. In conclusion, aldosterone blockade should form part of optimal therapy for patients with heart failure.
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