Eplerenone is a selective mineralocorticoid receptor antagonist with significantly less anti-androgenic activity than spironolactone. The EPHESUS trial showed mortality reduction in post-MI patients with heart failure, and EMPHASIS-HF demonstrated benefit in mild heart failure (NYHA II). It is preferred over spironolactone when gynecomastia or sexual side effects are a concern.
Reduces mortality post-MI with HF (EPHESUS trial)6,8
Reduces CV death and HF hospitalization in mild HF (EMPHASIS-HF)7
Selective MR antagonism, much lower gynecomastia risk than spironolactone6
Potassium-sparing diuresis
What to watch for
Hyperkalemia (most important adverse effect)
Dizziness
Diarrhea
Serum potassium >5.0 mEq/L at initiation
CrCl <30 mL/min (or <50 mL/min when used for hypertension)4
The bottom line
Evidence rating strong. Most-documented uses: reduces mortality post-mi with hf (ephesus trial), reduces cv death and hf hospitalization in mild hf (emphasis-hf), selective mr antagonism, much lower gynecomastia risk than spironolactone. 10 sources indexed (2022–2026), with 1 interaction record on file.
The science
How it works, mechanistically.
Core mechanism
Selectively blocks the mineralocorticoid (aldosterone) receptor with ~500-fold lower affinity for androgen and progesterone receptors compared to spironolactone. Blocks aldosterone-mediated sodium reabsorption and potassium excretion in the collecting duct. In heart failure, prevents aldosterone-driven cardiac fibrosis, inflammation, and vascular remodeling. The selectivity accounts for the markedly lower rate of gynecomastia and sexual side effects.8,6
Class
Selective Mineralocorticoid Receptor Antagonist
Dosing
Dosing & protocol.
Common range
25–50 mg once daily (as prescribed by your physician)
Recommended form
Oral tablet
Can be taken with or without food; food does not significantly affect absorption
Safety
Full safety detail.
Side effects
Hyperkalemia (most important adverse effect)
Dizziness
Diarrhea
Cough
Fatigue
Hyponatremia
Contraindications
Serum potassium >5.0 mEq/L at initiation
CrCl <30 mL/min (or <50 mL/min when used for hypertension)4
Type 2 diabetes with microalbuminuria and serum creatinine >2.0 mg/dL (males) or >1.8 mg/dL (females)10
Eplerenone is a mineralocorticoid receptor antagonist that can raise serum potassium. Adding potassium supplements can push potassium into a dangerous range, especially in kidney disease, diabetes, heart failure, older age, or when ACE inhibitors, ARBs, NSAIDs, or trimethoprim are also used. Severe hyperkalemia can cause weakness, paralysis, dangerous arrhythmias, or cardiac arrest.
Recommendation: Do not take potassium supplements with eplerenone unless your prescriber specifically orders them and monitors potassium. Avoid potassium-based salt substitutes, and check potassium and kidney function shortly after starting or changing eplerenone.
Bagattoli V, Dos Santos HS, Giorgi J et al.. Finerenone, Eplerenone, and Spironolactone in HFpEF: A Bayesian Network Meta-Analysis of Efficacy and Safety. European journal of heart failure. 2026
Huang RS, Mihalache A, Benour A et al.. Eplerenone and Spironolactone for Chronic Central Serous Chorioretinopathy: A Systematic Review and Meta-Analysis. American journal of ophthalmology. 2025
Elshahat A, Mansour A, Ellabban M et al.. Comparative effectiveness and safety of eplerenone and spironolactone in patients with heart failure: a systematic review and meta-analysis. BMC cardiovascular disorders. 2024
Hu H, Cao M, Sun Y et al.. Efficacy and Safety of Eplerenone for Treating Chronic Kidney Disease: A Meta-Analysis. International journal of hypertension. 2023
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