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

From the Guidelines

Eplerenone should be used at a starting dose of 25 mg once daily, which may be increased to 50 mg daily after a month, in patients with heart failure with reduced ejection fraction (HFrEF) and NYHA class II to IV symptoms, if eGFR is >30 mL/min/1.73 m2 and serum potassium is <5.0 mEq/L, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. The use of eplerenone in patients with HFrEF has been shown to reduce morbidity and mortality, with a high economic value, as demonstrated by the RALES, EPHESUS, and EMPHASIS-HF trials 1.

• The medication works by blocking aldosterone receptors in the kidneys, preventing sodium reabsorption and water retention while preserving potassium levels.
• Common side effects include elevated potassium levels (hyperkalemia), dizziness, and fatigue.
• Regular monitoring of potassium levels and kidney function is essential during treatment, with checks performed approximately 1 week, then 4 weeks, then every 6 months after initiating or intensifying eplerenone therapy.
• Eplerenone should be taken at the same time each day with or without food, and patients should maintain consistent potassium intake while using this medication.
• It's contraindicated in patients with severe kidney impairment, high potassium levels, or those taking strong CYP3A4 inhibitors like ketoconazole.
• The 2022 AHA/ACC/HFSA guideline recommends careful monitoring of potassium, renal function, and diuretic dosing at initiation and closely monitored thereafter to minimize risk of hyperkalemia and renal insufficiency 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 indicated for use 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

Clinical Use

• Eplerenone is used as adjunctive therapy for patients with heart failure following myocardial infarction 2
• It is also indicated for the treatment of mild and moderate essential hypertension for patients who cannot be treated adequately with other agents 2
• The daily doses of eplerenone ranged from 25 mg to 400 mg daily 2

Efficacy

• Meta-analysis of studies showed a reduction in systolic blood pressure of 9.21 mmHg (95% CI -11.08 to -7.34; I2 = 58%) and a reduction of diastolic pressure of 4.18 mmHg (95% CI -5.03 to -3.33; I2 = 0%) 2
• Eplerenone 50 to 200 mg/day lowers blood pressure in people with primary hypertension by 9.21 mmHg systolic and 4.18 mmHg diastolic compared to placebo, with no difference of effect between doses of 50 mg/day to 200 mg/day 2
• Treatment with eplerenone has been associated with reductions in blood pressure and improved survival (15% reduction in total mortality) for patients with heart failure who are in stable condition after a myocardial infarction 3

Safety and Side Effects

• The most severe side effect of spironolactone, hyperkalemia, was also observed with eplerenone 3, 4, 5
• Eplerenone is generally well tolerated, although hyperkalemia with this agent is of some concern 4, 5, 6
• The risk of hyperkalemia can be managed through careful selection and monitoring of patients 6