====== Eplerenone ======

Eplerenone is a selective [[cardio:diuretics:mra|Mineralocorticoid Receptor Antagonist (MRA)]].

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

Used in:

  * [[cardio:heart_failure:start|Heart Failure with Reduced EF]]
  * Post–myocardial infarction with LV dysfunction
  * Resistant [[cardio:hypertension:start|Hypertension]]

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===== Mechanism of Action =====

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.

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===== Renal Effects =====

Site:
  * Collecting duct

Effects:

  * Mild natriuresis
  * ↑ Potassium retention

Diuretic strength:
  * Weak compared to [[cardio:diuretics:loop:start|Loop Diuretics]]

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===== Clinical Use =====

HFrEF:

  * Mortality reduction
  * Added to:
      * [[cardio:raas:acei|ACE Inhibitors]] or [[cardio:raas:arb|ARBs]]
      * [[cardio:raas:arni|ARNI]]
      * [[cardio:beta_blockers:start|Beta-Blockers]]
      * [[endocrine:sglt2:start|SGLT2 Inhibitors]]

Post-MI LV Dysfunction:

  * Reduces mortality
  * Reduces sudden cardiac death

Resistant Hypertension:

  * Alternative to [[cardio:hf:spironolactone|Spironolactone]]

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===== Mortality Data =====

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

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===== Adverse Effects =====

Electrolytes:

  * Hyperkalemia
  * Mild hyponatremia

Compared to [[cardio:hf:spironolactone|Spironolactone]]:

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

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===== Contraindications =====

Avoid in:

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

Use caution when combined with:

  * [[cardio:raas:acei|ACE Inhibitors]]
  * [[cardio:raas:arb|ARBs]]
  * [[cardio:raas:direct_renin_inhibitor|Direct Renin Inhibitors]]

Monitor:

  * Potassium
  * Renal function

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===== Eplerenone vs Spironolactone =====

[[cardio:hf:spironolactone|Spironolactone]]:

  * Less selective
  * Causes gynecomastia
  * More commonly used

Eplerenone:

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

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===== Clinical Pearls =====

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

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===== Related =====

  * [[cardio:heart_failure:start|Heart Failure]]
  * [[cardio:hf:spironolactone|Spironolactone]]
  * [[cardio:diuretics:mra|Potassium-Sparing Diuretics]]
  * [[cardio:raas:acei|ACE Inhibitors]]