What is the use of Eplerenone (an aldosterone antagonist)?

From the Guidelines

Eplerenone should be used to treat patients with heart failure with reduced ejection fraction (HFrEF) and NYHA class II to IV symptoms, with a starting dose of 25 mg once daily, which may be increased to 50 mg daily after a month, as it has been shown to reduce morbidity and mortality in these patients, as demonstrated in the EMPHASIS-HF trial 1 and supported by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.

Key Considerations for Eplerenone Use

• Eplerenone is a potassium-sparing diuretic and selective aldosterone receptor antagonist that works by blocking the effects of aldosterone, a hormone that can increase blood pressure and worsen heart failure by promoting sodium retention and potassium loss.
• The medication is particularly valuable for patients with heart failure following myocardial infarction and those with resistant hypertension.
• Unlike spironolactone (another aldosterone antagonist), eplerenone causes fewer hormonal side effects such as gynecomastia in men.
• Important monitoring includes regular checks of potassium levels and kidney function, as hyperkalemia is a significant risk, especially in patients with kidney impairment.
• Eplerenone should be used cautiously with other medications that increase potassium and is contraindicated in patients with severe kidney dysfunction, type 2 diabetes with microalbuminuria, or serum potassium levels above 5.5 mEq/L.

Dosing and Administration

• The starting dose of eplerenone is 25 mg orally daily, which may be increased to 50 mg daily after a month.
• For patients with an estimated glomerular filtration rate (eGFR) of 31 to 49 mL/min/1.73 m2, the dosing should be reduced by half.
• Regular checks of serum potassium levels and renal function should be performed according to clinical status, approximately 1 week, then 4 weeks, then every 6 months after initiating or intensifying eplerenone, with more frequent testing for clinical instability.

Clinical Evidence

• The EMPHASIS-HF trial demonstrated that eplerenone reduces the risk of cardiovascular death or heart failure hospitalization by 37% in patients with systolic heart failure and mild symptoms 1.
• The 2022 AHA/ACC/HFSA guideline for the management of heart failure recommends the use of mineralocorticoid receptor antagonists (MRAs), including eplerenone, in patients with HFrEF and NYHA class II to IV symptoms, as it provides high economic value and reduces morbidity and mortality 1.
• The EPHESUS study also demonstrated the benefits of adding eplerenone to ACE inhibitors or ARBs and beta blockers in post-MI patients with heart failure, with a 15% and 17% reduction in overall and cardiovascular mortality, respectively 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Eplerenone Overview

• Eplerenone is an aldosterone receptor blocker used for the treatment of hypertension and heart failure 2, 3, 4, 5, 6.
• It is chemically derived from spironolactone and has a more selective action on the aldosterone receptor, resulting in fewer side effects such as gynecomastia and vaginal bleeding 3, 4.

Clinical Uses

• Eplerenone is indicated for the treatment of mild and moderate essential hypertension in patients who cannot be treated adequately with other agents 2.
• It is also used as adjunctive therapy to reduce mortality for heart failure patients with New York Heart Association (NYHA) class II systolic chronic heart failure and left ventricular systolic dysfunction 2.
• Additionally, eplerenone has been shown to be beneficial in reducing morbidity and mortality in individuals with left ventricular dysfunction post myocardial infarction 5, 6.

Efficacy and Safety

• Eplerenone has been shown to lower blood pressure in people with primary hypertension by 9.21 mmHg systolic and 4.18 mmHg diastolic compared to placebo 2.
• The most common side effect of eplerenone is hyperkalemia, which necessitates close monitoring in individuals with diabetes and proteinuria, heart failure, or those taking moderate CYP450 3A4 inhibitors 5.
• Eplerenone is generally well tolerated, with a similar antihypertensive efficacy to other antihypertensive agents 4.

Comparison to Spironolactone

• Eplerenone is a selective aldosterone receptor antagonist, whereas spironolactone is a non-selective antagonist, which can cause sex hormone-related adverse effects such as gynecomastia 3, 4.
• The American College of Cardiology recommends trying spironolactone first and then switching to eplerenone if patients develop gynecomastia, menstrual irregularities, or impotence 3.
• Eplerenone has been shown to have a similar efficacy to spironolactone in clinical trials, but with fewer side effects 3, 4.