Is spironolactone effective for systolic heart failure?

From the Guidelines

Spironolactone is effective for systolic heart failure, particularly in patients with severe heart failure and reduced ejection fraction, as it has been shown to reduce mortality and hospitalizations. The use of spironolactone in systolic heart failure is supported by the results of the RALES trial, which demonstrated a 30% relative risk reduction in death and a 35% relative risk reduction in hospital admission for worsening heart failure in patients with severe heart failure and reduced ejection fraction 1.

Key Considerations

• The medication should be used with caution in patients with kidney dysfunction or elevated potassium levels, as it can cause hyperkalemia and worsening renal function.
• Patients should be carefully monitored for potassium levels and kidney function, especially when initiating or titrating the medication.
• The starting dose of spironolactone is typically 12.5 to 25 mg once daily, with potential titration up to 50 mg daily if needed.

Benefits and Risks

• The benefits of spironolactone in systolic heart failure include reduced mortality and hospitalizations, as well as improved symptoms and quality of life.
• The risks of spironolactone include hyperkalemia, worsening renal function, and common side effects such as gynecomastia and menstrual irregularities.

Recent Guidelines

• The 2022 AHA/ACC/HFSA guideline for the management of heart failure recommends the use of mineralocorticoid receptor antagonists (MRAs) such as spironolactone in patients with heart failure with reduced ejection fraction (HFrEF) 1.
• The guideline also notes that the use of MRAs in patients with heart failure with preserved ejection fraction (HFpEF) may be beneficial in selected patients, but the evidence is less clear.

From the FDA Drug Label

The Randomized Spironolactone Evaluation Study was a placebo controlled, double-blind study of the effect of spironolactone on mortality in patients with highly symptomatic heart failure and reduced ejection fraction Compared to placebo, spironolactone reduced the risk of death by 30% (p<0. 001; 95% confidence interval 18% to 40%). Spironolactone also reduced the risk of hospitalization for cardiac causes (defined as worsening heart failure, angina, ventricular arrhythmias, or myocardial infarction) by 30% (p <0. 001; 95% confidence interval 18% to 41%). Spironolactone tablets are indicated for treatment of NYHA Class III-IV heart failure and reduced ejection fraction to increase survival, manage edema, and reduce the need for hospitalization for heart failure.

Spironolactone is effective for systolic heart failure with reduced ejection fraction, as it reduces the risk of death and hospitalization for cardiac causes 2. The primary benefit of spironolactone is to increase survival and reduce the need for hospitalization in patients with NYHA Class III-IV heart failure and reduced ejection fraction 2. Key points include:

• Reduced risk of death by 30%
• Reduced risk of hospitalization for cardiac causes by 30%
• Indicated for treatment of NYHA Class III-IV heart failure and reduced ejection fraction

From the Research

Effectiveness of Spironolactone for Systolic Heart Failure

• Spironolactone has been shown to be beneficial in patients with heart failure with reduced ejection fraction, reducing morbidity and mortality 3, 4, 5.
• The RALES trial demonstrated that spironolactone, in addition to standard therapy, is very beneficial in heart failure with a reduced ejection fraction 3.
• A study published in The American Journal of Cardiology found that spironolactone was not associated with a risk of hospitalization or death in patients with newly diagnosed systolic heart failure 5.
• However, another study found that spironolactone was associated with a 3.5-fold increased risk of hyperkalemia, but not with acute kidney injury 5.

Safety and Tolerability of Spironolactone

• A retrospective cohort study evaluated the safety and tolerability of spironolactone in patients with heart failure and chronic kidney disease, and found that spironolactone may be safe to initiate in hospitalized patients with heart failure and chronic kidney disease 4.
• The study also found that patients who experienced inpatient hyperkalemia had a numerically lower eGFR, but this was not statistically significant 4.
• Another study found that the administration of spironolactone was associated with an increase in readmissions in patients with heart failure and preserved ejection fraction, possibly due to a higher rate of hyperpotassemia 6.

Patient Selection and Perspectives

• Spironolactone has been shown to be effective in patients with heart failure with reduced ejection fraction, and may also offer symptomatic relief in patients with heart failure and preserved ejection fraction 7.
• Patient selection is important, as spironolactone may not be suitable for all patients, particularly those with chronic kidney disease or hyperkalemia 4, 5, 6.
• A liquid suspension formulation of spironolactone has been approved by the FDA, which may enable more patients to benefit from this therapy, particularly those who have difficulty swallowing tablets 7.