Is spironolactone indicated in patients with an ejection fraction (EF) of 50-55%?

Spironolactone Use in Patients with EF 50-55%

Spironolactone may be considered in selected patients with an ejection fraction of 50-55%, particularly those with elevated BNP levels or recent heart failure hospitalization, but it is not routinely recommended for all patients in this EF range. 1

Evidence-Based Recommendation

The 2017 ACC/AHA/HFSA guidelines provide the most recent and relevant guidance on this topic. For patients with heart failure with preserved ejection fraction (HFpEF, which includes EF 50-55%):

• Spironolactone might be considered in appropriately selected symptomatic patients with:
  • EF ≥45%
  • Elevated BNP level or heart failure admission within 1 year
  • eGFR >30 mL/min
  • Creatinine <2.5 mg/dL
  • Potassium <5.0 mEq/L 1

Clinical Decision Algorithm

1. Determine if patient meets criteria for spironolactone consideration:

   • Confirmed heart failure symptoms
   • EF 50-55% (falls within HFpEF range)
   • At least one of:
     • Elevated BNP/NT-proBNP
     • Heart failure hospitalization within past year

2. Check for contraindications:

   • eGFR ≤30 mL/min
   • Creatinine ≥2.5 mg/dL in men or ≥2.0 mg/dL in women
   • Potassium ≥5.0 mEq/L

3. If eligible, initiate at low dose:

   • Start at 25 mg daily (or 15 mg if concerns about tolerability) 2
   • Monitor potassium and renal function after 5-7 days 1
   • Titrate dose based on laboratory results

Evidence Analysis

The TOPCAT trial is the key study evaluating spironolactone in HFpEF. While the overall trial did not show a statistically significant reduction in the primary composite endpoint, post-hoc analyses revealed:

• Hospitalization for heart failure was reduced (HR=0.83) 1, 3
• Patients in the Americas showed benefit (HR=0.83) while those in Russia/Georgia did not 1
• Patients with lower EF (closer to 45%) appeared to benefit more 1

The 2022 AHA/ACC/HFSA guidelines note that post-hoc analyses of TOPCAT suggest potential benefit in the lower EF range of HFpEF, particularly for patients with EF 44-49% 1.

Practical Implementation

• Dosing: The median dose in TOPCAT was approximately 22.5 mg/day, with high-risk patients (elderly, renal dysfunction, higher baseline potassium) typically receiving lower doses around 20 mg/day 2

• Monitoring:

  • Check potassium and renal function 5-7 days after initiation
  • Recheck every 5-7 days until values stabilize
  • Then monitor every 3-6 months 1

• Side effects to monitor:

  • Hyperkalemia (occurred in 18.7% vs 9.1% with placebo in TOPCAT) 3
  • Worsening renal function
  • Gynecomastia (in men)

Important Caveats

• Discontinuation rates in high-risk subgroups reached 30% during the first year in TOPCAT 2
• If patients cannot tolerate target doses, a low-dose strategy is preferable to discontinuation 2
• Spironolactone improved diastolic function in some studies but did not consistently improve exercise capacity or quality of life 4
• Careful monitoring of potassium, renal function, and diuretic dosing is essential to minimize risks 1

The decision to use spironolactone in patients with EF 50-55% should be guided by the presence of heart failure symptoms, recent hospitalization or elevated natriuretic peptides, and absence of contraindications, with close monitoring of renal function and electrolytes.