What is the place for Mineralocorticoid Receptor Antagonists (MRAs) in patient management?

From the Guidelines

Mineralocorticoid Receptor Antagonists (MRAs) have a well-established place in the management of patients with heart failure with reduced ejection fraction (HFrEF), and their use is recommended to reduce morbidity and mortality in these patients, as supported by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. The primary indications for MRAs include HFrEF, resistant hypertension, and primary hyperaldosteronism.

• The main MRAs used clinically are spironolactone and eplerenone, with starting doses of 25 mg daily and maximum doses of 50 mg daily for both medications.
• For heart failure patients, MRAs should be added to standard therapy including ACE inhibitors/ARBs and beta-blockers when patients remain symptomatic despite these medications.
• In resistant hypertension, MRAs are typically added as a fourth-line agent when blood pressure remains uncontrolled on three different antihypertensive medications.
• When prescribing MRAs, regular monitoring of serum potassium and renal function is essential, particularly within 1-2 weeks of initiation and after dose adjustments, as emphasized in the 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure 1.
• These medications should be used cautiously or avoided in patients with significant renal impairment (eGFR <30 ml/min) or hyperkalemia (K+ >5.0 mEq/L), as highlighted in the European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 1.
• MRAs work by blocking aldosterone receptors, reducing sodium reabsorption and potassium excretion in the distal tubule, which helps manage fluid retention and counteracts the harmful cardiovascular effects of excess aldosterone, including myocardial fibrosis and vascular inflammation. The use of MRAs in patients with heart failure with preserved ejection fraction (HFpEF) may be considered in appropriately selected patients, as suggested by the 2017 ACC/AHA/HFSA focused update 1, but their effectiveness in this population is less clear and requires further study. Overall, the use of MRAs in clinical practice should be guided by the most recent and highest-quality evidence, with careful consideration of the potential benefits and risks in individual patients, as recommended by the European Journal of Heart Failure 1.

From the FDA Drug Label

Eplerenone binds to the mineralocorticoid receptor and blocks the binding of aldosterone, a component of the renin-angiotensin-aldosterone-system (RAAS). Spironolactone and its active metabolites are specific pharmacologic antagonists of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule.

The place for Mineralocorticoid Receptor Antagonists (MRAs) in patient management is in the treatment of conditions such as:

• Heart Failure: MRAs like eplerenone have been shown to reduce mortality and morbidity in patients with heart failure post-myocardial infarction.
• Hypertension: MRAs like spironolactone and eplerenone can be used to treat resistant hypertension.
• Edematous states: MRAs like spironolactone can be used to treat edema and ascites in conditions such as congestive heart failure, hepatic cirrhosis, and nephrotic syndrome. MRAs work by blocking the effects of aldosterone, a hormone that promotes sodium retention and potassium excretion, leading to increased blood pressure and fluid retention. By blocking aldosterone, MRAs can help to reduce blood pressure, decrease fluid retention, and improve outcomes in patients with heart failure and other conditions. 2 2 3

From the Research

Place for Mineralocorticoid Receptor Antagonists (MRAs) in Patient Management

The place for MRAs in patient management can be summarized as follows:

• MRAs are recommended for patients with heart failure (HF) and reduced ejection fraction (HFrEF), as they improve survival and reduce morbidity 4, 5.
• MRAs are also beneficial for patients with mild HF symptoms, as they reduce the risk of cardiovascular death or HF hospitalization 4.
• The efficacy of MRAs in patients with HFmrEF or HFpEF is less clear, but they may still reduce the risk of hospitalization for HF or cardiovascular death 6.
• MRAs can be used in patients with chronic kidney disease (CKD) to reduce cardiovascular morbidity and mortality, but their use in advanced CKD is not recommended due to the risk of acute kidney injury or hyperkalemia 7.
• Initiation of MRAs during hospital admission for acute HF is associated with improved outcomes, regardless of ejection fraction 8.

Key Patient Populations for MRAs

Key patient populations for MRAs include:

• Patients with HF and reduced ejection fraction (HFrEF) 4, 5.
• Patients with mild HF symptoms 4.
• Patients with CKD, although caution is needed in advanced CKD 7.
• Patients hospitalized for acute HF, regardless of ejection fraction 8.

Important Considerations for MRA Use

Important considerations for MRA use include:

• Close monitoring of renal function and serum potassium 4, 5.
• Dose selection based on renal function, baseline potassium, and concomitant drug interactions 4.
• Risk of hyperkalemia, although this can be mitigated with appropriate patient selection and monitoring 5, 6.