What is the benefit of Aldactone (spironolactone) in heart failure?

Aldactone (Spironolactone) in Heart Failure

Aldactone significantly reduces mortality by 30% and heart failure hospitalizations by 30-42% in patients with symptomatic systolic heart failure (NYHA class III-IV) with reduced ejection fraction (≤35%), and should be added to standard therapy with ACE inhibitors and diuretics in these patients. 1, 2

Mortality and Hospitalization Benefits

For severe heart failure (NYHA III-IV):

• The landmark RALES trial demonstrated a 30% relative risk reduction in all-cause mortality in patients with EF ≤35% and NYHA class III-IV symptoms 1, 2
• The absolute risk reduction in mortality was 11.4% after 2 years, translating to a number needed to treat of 9 to prevent one death 1
• Heart failure hospitalizations were reduced by 35% 1
• These benefits were additional to those achieved with ACE inhibitors and diuretics 1, 2

For mild heart failure (NYHA II):

• The EMPHASIS-HF trial extended benefits to patients with milder symptoms (NYHA class II) and EF ≤30-35% 1
• Eplerenone (a selective aldosterone antagonist) reduced cardiovascular death or heart failure hospitalization by 37% 1
• All-cause mortality was reduced by 24%, and heart failure hospitalizations by 42% 1

Recommended Patient Population

Initiate spironolactone in patients meeting ALL of the following criteria: 1, 2

• Left ventricular ejection fraction ≤35%
• NYHA functional class III-IV symptoms (or class II with elevated risk features)
• Already receiving optimal doses of ACE inhibitor (or ARB) and beta-blocker
• Serum potassium ≤5.0 mEq/L
• Serum creatinine ≤2.5 mg/dL (or creatinine clearance adequate)

Dosing Algorithm

Starting dose: 25 mg once daily 1, 2

Titration schedule: 1

• Check renal function and potassium at 1 week and 4 weeks after initiation
• If tolerated at 8 weeks, may increase to 50 mg once daily (target dose)
• If intolerant, reduce to 25 mg every other day
• The mean effective dose in RALES was 26 mg daily 2

Monitoring Requirements

Critical safety monitoring to prevent hyperkalemia and renal dysfunction: 1, 3

• Check serum potassium and creatinine before initiation
• Recheck at 1 week, 4 weeks, then every 3 months for the first year 1, 2
• Subsequently monitor every 6 months 1, 2

Stop spironolactone immediately if: 1

• Serum potassium rises above 5.5 mEq/L
• Serum creatinine increases by >100% or exceeds 4 mg/dL (354 μmol/L)

Common Pitfalls and Caveats

Risk of hyperkalemia in real-world practice:

• While clinical trials showed manageable hyperkalemia rates, post-RALES observational data revealed a striking increase in hyperkalemia-related hospitalizations and mortality when used in unselected populations 1
• This occurred particularly in elderly patients (mean age 78 years) who received less rigorous monitoring than trial participants 1
• Spironolactone carries a 3.5-fold increased risk of severe hyperkalemia compared to non-use 4

Patient selection is critical:

• Exclude patients with baseline creatinine >2.5 mg/dL or potassium >5.0 mEq/L 1, 2
• Use extreme caution in elderly patients, who were underrepresented in trials 1
• Avoid concomitant potassium supplements and potassium-sparing diuretics 1
• Avoid NSAIDs, which increase hyperkalemia risk 1

Adverse effects:

• Gynecomastia occurs in approximately 10% of men taking spironolactone 1
• If painful gynecomastia develops, consider switching to eplerenone, which has lower affinity for androgen receptors 1, 3

Evidence Quality Considerations

The 2012 ESC guidelines represent the most recent comprehensive guideline evidence, incorporating both RALES (severe HF) and EMPHASIS-HF (mild HF) data 1. The FDA label confirms these benefits and provides specific dosing guidance 2. However, real-world effectiveness studies suggest benefits may be attenuated compared to clinical trials, with one community-based cohort showing no independent association with reduced hospitalization or mortality 4. This divergence emphasizes the critical importance of careful patient selection and rigorous monitoring to replicate trial benefits while avoiding the hyperkalemia complications observed in broader clinical practice 1, 4.