Related Experiment Videos
"Escape" of aldosterone production in patients with left ventricular dysfunction treated with an angiotensin
1Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, USA.
Insights
Blocking aldosterone may improve outcomes for patients with heart failure. Aldosterone "escape" despite ACE inhibitors causes harm, but aldosterone antagonists like spironolactone show promise in improving symptoms and reducing mortality.
Area of Science:
- Cardiology
- Pharmacology
- Internal Medicine
Background:
- Angiotensin-converting enzyme (ACE) inhibitors reduce morbidity and mortality in patients with left ventricular dysfunction but do not fully suppress aldosterone.
- Aldosterone "escape" during ACE inhibitor therapy contributes to sodium retention, potassium loss, myocardial collagen production, and ventricular hypertrophy.
- Elevated aldosterone levels correlate significantly with mortality in heart failure patients.
Purpose of the Study:
- To evaluate the safety of blocking aldosterone effects in heart failure patients already treated with an ACE inhibitor.
- To investigate the role of aldosterone blockade in improving outcomes for patients with symptomatic left ventricular dysfunction.
Main Methods:
- The Randomized Aldactone Evaluation Study (RALES Pilot Study) is an international, prospective, multicenter trial.
- The study assesses the safety of spironolactone, an aldosterone antagonist, in heart failure patients on conventional therapy including an ACE inhibitor.
Main Results:
- Spironolactone administration resulted in increased diuresis and symptomatic improvement in heart failure patients.
- Preliminary findings suggest potential benefits of aldosterone blockade in this patient population.
Conclusions:
- Aldosterone blockade is a potential strategy to further improve outcomes in heart failure patients treated with ACE inhibitors.
- The RALES Pilot Study aims to confirm the safety and efficacy of aldosterone antagonists in managing heart failure.
Abstract:
Despite the findings in randomized trials of a significant effect of angiotensin-converting enzyme (ACE) inhibitors in reducing morbidity and mortality of patients with symptomatic left ventricular dysfunction, the morbidity and mortality of these patients remains relatively high. One potential strategy to further improve morbidity and mortality in these patients is blockade of a aldosterone. Many clinicians have assumed that ACE inhibitors would block both angiotensin II and aldosterone. However, there are data to suggest that aldosterone production may "escape" despite the use of an ACE inhibitor. An escape of aldosterone production has several important consequences, including: sodium retention, potassium and magnesium loss, myocardial collagen production, ventricular hypertrophy, myocardial norepinephrine release, endothelial dysfunction, and a decrease in serum high density lipoprotein cholesterol. Due to the potential importance of these mechanisms, the finding that there is a significant correlation between aldosterone production and mortality in patients with heart failure, as well as evidence that an aldosterone antagonist, spironolactone, when administered to patients with heart failure treated with conventional therapy including an ACE inhibitor results in increased diuresis and symptomatic improvement, an international prospective multicenter study has been organized, the Randomized Aldactone Evaluation Study (RALES Pilot Study), to evaluate the safety of blocking the effects of aldosterone in patients with heart failure treated with an ACE inhibitor.