Eplerenone

Eplerenone is a selective Mineralocorticoid Receptor Antagonist (MRA).

It blocks aldosterone at the collecting duct and reduces cardiac remodeling.

Used in:

• Heart Failure with Reduced EF
• Post–myocardial infarction with LV dysfunction
• Resistant Hypertension

Eplerenone selectively antagonizes the mineralocorticoid (aldosterone) receptor.

Aldosterone normally:

• ↑ ENaC expression
• ↑ Sodium reabsorption
• ↑ Potassium secretion
• Promotes myocardial fibrosis and remodeling

Blocking aldosterone results in:

• ↓ Sodium reabsorption
• ↑ Potassium retention
• ↓ Ventricular remodeling
• ↓ Fibrosis

The mortality benefit is due to neurohormonal modulation — not diuresis alone.

Site:

• Collecting duct

Effects:

• Mild natriuresis
• ↑ Potassium retention

Diuretic strength:

• Weak compared to Loop Diuretics

HFrEF:

• Mortality reduction
• Added to:
  • ACE Inhibitors or ARBs
  • ARNI
  • Beta-Blockers
  • SGLT2 Inhibitors

Post-MI LV Dysfunction:

• Reduces mortality
• Reduces sudden cardiac death

Resistant Hypertension:

• Alternative to Spironolactone

EPHESUS Trial:

• Reduced mortality post-MI with LV dysfunction

EMPHASIS-HF Trial:

• Reduced mortality in mild HFrEF

Benefit driven by:

• Reduced remodeling
• Reduced arrhythmogenic fibrosis

Electrolytes:

• Hyperkalemia
• Mild hyponatremia

Compared to Spironolactone:

• Less gynecomastia
• Fewer endocrine effects
• More selective receptor profile

Avoid in:

• Severe renal impairment
• Baseline hyperkalemia
• Concomitant strong CYP3A4 inhibitors

Use caution when combined with:

• ACE Inhibitors
• ARBs
• Direct Renin Inhibitors

Monitor:

• Potassium
• Renal function

Spironolactone:

• Less selective
• Causes gynecomastia
• More commonly used

Eplerenone:

• More selective MRA
• Fewer endocrine side effects
• Preferred post-MI

• Selective MRA
• Reduces mortality in HFrEF
• Reduces mortality post-MI
• Causes hyperkalemia
• Less gynecomastia than spironolactone
• Neurohormonal benefit > diuretic effect

• Heart Failure
• Spironolactone
• Potassium-Sparing Diuretics
• ACE Inhibitors