Benefits of Aldactone (Spironolactone) Over Eplerenone
Spironolactone is more potent than eplerenone as a mineralocorticoid receptor antagonist and should be considered first-line when maximum efficacy is needed, particularly in advanced heart failure. 1, 2
Comparative Efficacy
- Spironolactone is currently the most potent mineralocorticoid receptor (MR) antagonist used in clinical practice 1
- The RALES mortality trial demonstrated that low-dose spironolactone (12.5-50 mg) markedly improved survival in patients with advanced heart failure (NYHA class III or IV) 1
- Spironolactone has been proven to reduce both death from progressive heart failure and sudden cardiac death 1
Pharmacological Differences
- Spironolactone has active metabolites with longer half-lives, potentially providing more sustained therapeutic effects 3
- Eplerenone was designed with the addition of a 9,11-epoxide group to be more selective for the mineralocorticoid receptor 2
- Eplerenone has a shorter half-life and no active metabolites, potentially requiring more frequent dosing 3
Clinical Applications
Heart Failure
- Aldosterone antagonism with spironolactone is specifically recommended in advanced heart failure (NYHA III-IV) to improve survival and morbidity (level of evidence B) 1
- Spironolactone at low doses (12.5-50 mg) on top of an ACE inhibitor and loop diuretic has demonstrated mortality benefit 1
- Eplerenone has shown benefit in post-myocardial infarction patients with systolic heart failure 2
Hypertension
- Both drugs are effective in treating hypertension 4
- Spironolactone is recommended at doses of 25-100 mg daily for hypertension 1
- Eplerenone is dosed at 50-100 mg daily, sometimes requiring twice-daily dosing for adequate BP lowering 1
Side Effect Profiles
Spironolactone Disadvantages
- Higher incidence of endocrine side effects (>10% of patients) including:
Eplerenone Advantages
- More selective for mineralocorticoid receptors with minimal effect on other steroid receptors 2
- Significantly lower incidence of hormone-related side effects 4
- Recommended as an alternative to spironolactone when gynecomastia is a concern 5
Cost Considerations
- After patent expiration of eplerenone, the price difference between the two medications has become negligible 1
- Cost should no longer be a major factor in decision-making between these agents
Monitoring Requirements
- Both medications require monitoring of serum potassium and renal function 1
- Risk of hyperkalemia exists with both agents, particularly in at-risk patients:
- Diabetes mellitus
- Kidney/liver disorders
- Elderly patients
- Concomitant use of potassium supplements or other potassium-sparing medications 1
Clinical Decision Algorithm
For maximum efficacy in advanced heart failure (NYHA III-IV):
- Choose spironolactone (12.5-50 mg daily) 1
For patients at risk of hormone-related side effects:
For patients with bilateral idiopathic hyperaldosteronism:
- Both agents show similar efficacy in BP control (76.5% with spironolactone vs 82.4% with eplerenone) 6
- Consider starting with eplerenone to avoid endocrine side effects
Common Pitfalls and Caveats
- Hyperkalemia is a risk with both medications and can be life-threatening 7
- Always check baseline potassium and renal function before initiating either medication
- Avoid concomitant use with other potassium-sparing diuretics, potassium supplements, or CYP3A4 inhibitors (particularly with eplerenone) 1
- Switching from spironolactone to eplerenone can resolve gynecomastia while maintaining blood pressure control 6
- Neither drug should be used in patients with severe renal impairment or baseline hyperkalemia (>5.5 mEq/L) 5