Which is better, eplerenone or spironolactone, for treating heart failure or resistant hypertension?

Eplerenone vs. Spironolactone: Which is Better for Heart Failure and Resistant Hypertension

Eplerenone is better than spironolactone for treating heart failure and resistant hypertension due to its more favorable side effect profile and recent evidence showing lower mortality rates, despite requiring twice-daily dosing in some cases. 1

Efficacy Comparison

• Both eplerenone and spironolactone are mineralocorticoid receptor antagonists (MRAs) that effectively treat heart failure and resistant hypertension 2
• The most recent meta-analysis (2024) demonstrated that eplerenone is associated with lower all-cause mortality (HR = 0.78) and cardiovascular mortality (HR = 0.54) compared to spironolactone in heart failure patients 1
• Both medications are considered preferred agents for treating primary aldosteronism and resistant hypertension 2
• Eplerenone often requires twice-daily dosing (50-100 mg/day) for adequate blood pressure control, while spironolactone typically requires only once-daily dosing (25-100 mg/day) 2

Side Effect Profile

• Spironolactone is associated with significantly higher risk of gynecomastia and impotence compared to eplerenone due to its non-selective binding to progesterone and androgen receptors 2
• Eplerenone was specifically designed with a 9,11-epoxide group to avoid the hormone-associated side effects of spironolactone 2
• The risk of gynecomastia with eplerenone is dramatically lower (RR = 0.07) compared to spironolactone 1
• Both medications carry similar risks of hyperkalemia, requiring monitoring of potassium levels and renal function 3, 4
• Treatment withdrawal is significantly less common with eplerenone (RR = 0.69) compared to spironolactone 1

Clinical Decision Algorithm

1. First-line choice: Eplerenone (50-100 mg/day) due to:

   • Lower all-cause and cardiovascular mortality 1
   • Significantly fewer endocrine side effects 3, 1
   • Lower treatment discontinuation rates 1

2. Dosing considerations:

   • Start eplerenone at 25mg once daily and titrate to target dose of 50mg daily within 4 weeks 3
   • May require twice-daily dosing in some patients for adequate BP control 2
   • Monitor serum potassium and renal function before and during therapy 3

3. Special populations:

   • Male patients particularly benefit from eplerenone due to minimal risk of gynecomastia and sexual dysfunction 2, 5
   • Avoid both medications in patients with significant renal dysfunction or those taking potassium supplements 2

Common Pitfalls and Caveats

• Despite eplerenone's advantages, some clinicians still prescribe spironolactone first due to:

  • Historical familiarity with spironolactone 6
  • Once-daily dosing convenience of spironolactone 2
  • Potentially lower cost of spironolactone in some regions 5

• Both medications require:

  • Monitoring of serum potassium levels and renal function 3, 4
  • Caution in patients with CKD or those taking other potassium-sparing medications 2
  • Avoidance in pregnancy 2

• If cost is a major concern, spironolactone remains a reasonable alternative, with the understanding that side effects may lead to discontinuation 6, 5