When to add Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure (HF)?

From the Guidelines

Mineralocorticoid Receptor Antagonists (MRAs) such as spironolactone or eplerenone should be added to heart failure treatment in patients with symptomatic heart failure with reduced ejection fraction (HFrEF) and NYHA class II to IV symptoms, if eGFR is >30 mL/min/1.73 m2 and serum potassium is <5.0 mEq/L, as recommended by the 2022 AHA/ACC/HFSA guideline 1.

Key Considerations

• The patient should have symptomatic HFrEF with NYHA class II to IV symptoms.
• The patient's eGFR should be greater than 30 mL/min/1.73 m2.
• The patient's serum potassium level should be less than 5.0 mEq/L.
• Close monitoring of potassium, renal function, and diuretic dosing should be performed at initiation and closely monitored thereafter to minimize risk of hyperkalemia and renal insufficiency.

Initiation and Monitoring

• The starting dose of spironolactone and eplerenone is 25 mg orally daily, increased to 50 mg daily orally after a month.
• For eGFR 31 to 49 mL/min/1.73 m2, dosing should be reduced by half.
• Regular checks of serum potassium levels and renal function should be performed according to clinical status, approximately 1 week, then 4 weeks, then every 6 months after initiating or intensifying MRA, with more frequent testing for clinical instability.

Benefits and Risks

• MRAs have been shown to decrease mortality, hospitalizations, and disease progression in heart failure patients 1.
• MRAs should be used cautiously in patients with kidney dysfunction and are contraindicated when potassium levels exceed 5.5 mEq/L or eGFR falls below 30 mL/min.

From the FDA Drug Label

2.1 Heart Failure Post-Myocardial Infarction Initiate treatment at 25 mg once daily and titrate to the recommended dose of 50 mg once daily, preferably within 4 weeks as tolerated by the patient.

The decision to add a Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure (HF) should be based on the patient's specific clinical condition.

• MRA therapy, such as eplerenone, is recommended for patients with HF with reduced ejection fraction (HFrEF) who have experienced a myocardial infarction, as it has been shown to reduce morbidity and mortality 2.
• The treatment should be initiated at a dose of 25 mg once daily and titrated to the recommended dose of 50 mg once daily, preferably within 4 weeks, as tolerated by the patient.
• It is essential to monitor serum potassium levels and adjust the dose accordingly to minimize the risk of hyperkalemia.
• The use of MRA in HF patients with other clinical profiles, such as those with preserved ejection fraction, is not directly addressed in the provided drug label and should be guided by other clinical guidelines and recommendations.

From the Research

When to Add MRA in HF

• Mineralocorticoid Receptor Antagonists (MRAs) are recommended for patients with moderate to severe heart failure (HF) symptoms and reduced left ventricular ejection fraction (LVEF), and in postmyocardial infarction patients with HF 3.
• MRAs are also recommended for patients with New York Heart Association (NYHA) Class II-IV symptoms and reduced LVEF (<35%) on standard therapy, with a strength of evidence A 3.
• For patients with NYHA Class II symptoms, another high-risk feature is required to be consistent with the EMPHASIS-HF population, such as age >55 years, QRS duration >130 msec, HF hospitalization within 6 months, or elevated B-type natriuretic peptide level 3.
• The efficacy of MRAs in patients with mild HF symptoms translates into a unique opportunity to reduce morbidity and mortality earlier in the course of the disease 3, 4.
• MRAs reduce the risk of cardiovascular death or heart failure hospitalization in patients with HFrEF, with a hazard ratio of 0.77 (95% CI 0.72-0.83) 5.
• The use of MRAs should be considered in patients with HF and impaired renal function, as they can reduce the risk of cardiovascular death or HF hospitalization, even in those with a decline in eGFR to <30 mL/min/1.73 m2 6.
• Education about the limited true risk associated with hyperkalemia and how to predict, prevent, and manage it may lead to wider acceptability and use of MRAs 7.

Key Patient Populations

• Patients with HFrEF: MRAs reduce the risk of cardiovascular death or heart failure hospitalization, with a hazard ratio of 0.66 (95% CI 0.59-0.73) 5.
• Patients with HFmrEF or HFpEF: MRAs may reduce the risk of heart failure hospitalization, but the evidence is less clear 5.
• Patients with impaired renal function: MRAs can reduce the risk of cardiovascular death or HF hospitalization, even in those with a decline in eGFR to <30 mL/min/1.73 m2 6.

Safety Considerations

• Hyperkalemia: MRAs can increase the risk of hyperkalemia, but the incidence of serious hyperkalemia is low 5, 6.
• Renal function: MRAs should be used with caution in patients with impaired renal function, and renal function should be closely monitored 3, 6.