What is the role of mineralocorticoid receptor agonists in the management of heart failure?

From the Guidelines

Mineralocorticoid receptor antagonists (MRAs), not agonists, are recommended for treating heart failure, as they have been shown to reduce morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF) 1. The primary MRAs used in HFrEF are spironolactone (25-50 mg daily) and eplerenone (25-50 mg daily), which should be added to standard therapy including ACE inhibitors/ARBs and beta-blockers. These medications block aldosterone's harmful effects, reducing cardiac fibrosis, sodium retention, and potassium excretion. When starting an MRA, it is essential to monitor potassium and renal function at baseline, 1 week, 1 month, and then quarterly, as recommended by the 2020 ACC/AHA clinical performance and quality measures for adults with heart failure 1. Patients with severe renal dysfunction (eGFR <30 mL/min) or hyperkalemia (K+ >5.0 mEq/L) should avoid these medications. Additionally, patients should be counseled about potential side effects, including gynecomastia (more common with spironolactone), hyperkalemia, and worsening renal function. MRAs have demonstrated significant mortality benefits in multiple large clinical trials, reducing death and hospitalizations in patients with symptomatic heart failure, as noted in the 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure 1. True mineralocorticoid receptor agonists would actually worsen heart failure by promoting fluid retention and cardiac remodeling. Key considerations for the use of MRAs in heart failure with preserved ejection fraction (HFpEF) include careful selection of patients, monitoring of potassium and renal function, and consideration of regional variation in treatment response, as highlighted in the TOPCAT trial 1. In summary, the use of MRAs is a crucial component of heart failure management, and their benefits in reducing morbidity and mortality make them a recommended treatment option for patients with HFrEF.

Some key points to consider when using MRAs in clinical practice include:

• Monitoring of potassium and renal function is essential to minimize the risk of hyperkalemia and worsening renal function 1.
• Patients with severe renal dysfunction or hyperkalemia should avoid MRAs 1.
• MRAs have been shown to reduce hospitalizations and improve outcomes in patients with HFrEF, but their use in HFpEF is more nuanced and requires careful patient selection and monitoring 1.
• The benefits of MRAs in reducing morbidity and mortality make them a recommended treatment option for patients with HFrEF, as noted in the 2020 ACC/AHA clinical performance and quality measures for adults with heart failure 1.

Overall, the use of MRAs is a critical component of heart failure management, and their benefits in reducing morbidity and mortality make them a recommended treatment option for patients with HFrEF.

From the Research

Mineralocorticoid Receptor Agonists in Heart Failure

• Mineralocorticoid receptor antagonists (MRAs) have been shown to improve survival and reduce morbidity in patients with heart failure, particularly those with reduced ejection fraction (HFrEF) 2, 3.
• The use of MRAs has been expanded to patients with heart failure and mildly reduced ejection fraction (HFmrEF) or heart failure and preserved ejection fraction (HFpEF), with some studies showing benefits in these populations 4, 5.
• MRAs have been found to reduce hospitalizations and death in patients with HFrEF, and to a lesser extent, in patients with HFmrEF or HFpEF 4.
• The benefits of MRAs are thought to be mediated by their antifibrotic mechanisms, which slow heart failure progression, prevent or reverse cardiac remodelling, and reduce arrhythmogenesis 3.

Mechanisms of Action

• MRAs work by blocking the effects of aldosterone, a hormone that promotes sodium retention and potassium vasopetamine, leading to increased blood pressure and cardiac workload 2.
• MRAs have been shown to attenuate the appearance of secondary hyperparathyroidism, which accompanies excretory Ca2+ losses induced by aldosteronism, and to reduce the risk of adverse cardiovascular events and atraumatic bone fracture 2.

Safety and Efficacy

• The use of MRAs has been limited due to concerns about hyperkalemia, but 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 these agents 5.
• MRAs have been found to be safe and effective in patients with heart failure, with a low incidence of serious hyperkalemia and a reduced risk of hypokalemia 4.

Future Directions

• Ongoing trials are testing steroidal and nonsteroidal MRAs in heart failure populations, and further research is needed to fully understand the benefits and risks of these agents 5, 6.
• The development of new nonsteroidal MRAs, such as esaxerenone and finerenone, may provide additional treatment options for patients with heart failure 6.