Do aldosterone inhibitors work in patients with hyperreninemia (elevated Renin (a hormone))?

From the Guidelines

Aldosterone inhibitors can be effective in patients with high renin levels, as they block the effects of aldosterone at the receptor level regardless of the cause of elevated aldosterone. These medications, including spironolactone and eplerenone, have been shown to reduce mortality and hospital admissions in patients with heart failure, as demonstrated in the RALES trial, where spironolactone led to a 30% relative risk reduction in death and a 35% relative risk reduction in hospital admission for worsening heart failure 1. The benefits of aldosterone inhibitors are thought to be due to their ability to counteract the harmful effects of aldosterone on the heart and kidneys, which are activated in high-renin states.

When using aldosterone inhibitors in patients with high renin levels, it is essential to monitor potassium levels and kidney function regularly, as hyperkalemia is a potential side effect, particularly in patients with impaired renal function or those taking other medications that affect potassium levels 1. The typical dosing for spironolactone ranges from 25-50 mg daily, as used in the RALES trial, while eplerenone is usually given at 25-50 mg daily, as used in the EPHESUS trial.

Key considerations when prescribing aldosterone inhibitors include:

• Monitoring potassium levels and kidney function regularly
• Avoiding high-potassium foods and potassium supplements
• Using these medications only in patients with adequate renal function and a normal serum potassium
• Being aware of the potential for hyperkalemia and worsening renal function, particularly in the elderly or those with pre-existing kidney disease 1.

Overall, aldosterone inhibitors can be a valuable addition to the treatment regimen for patients with high renin levels, particularly those with heart failure or resistant hypertension, as long as they are used judiciously and with careful monitoring of potential side effects.

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). Eplerenone has been shown to produce sustained increases in plasma renin and serum aldosterone, consistent with inhibition of the negative regulatory feedback of aldosterone on renin secretion The resulting increased plasma renin activity and aldosterone circulating levels do not overcome the effects of eplerenone.

Aldosterone inhibitors like eplerenone work by blocking the binding of aldosterone to mineralocorticoid receptors. In patients with high renin levels, the use of aldosterone inhibitors can lead to an increase in plasma renin activity. However, according to the drug label, this increase in plasma renin activity does not overcome the effects of eplerenone 2.

• The mechanism of action of eplerenone suggests that it can still be effective in patients with high renin levels.
• The pharmacodynamics of eplerenone indicate that it can produce sustained increases in plasma renin and serum aldosterone, but these increases do not affect its efficacy. Therefore, aldosterone inhibitors like eplerenone can work in patients with high renin levels 2.

From the Research

Effectiveness of Aldosterone Inhibitors on High Renin Patients

• The effectiveness of aldosterone inhibitors on high renin patients is not directly addressed in the provided studies 3, 4, 5, 6, 7.
• However, the studies suggest that aldosterone inhibitors, such as eplerenone and spironolactone, can be beneficial in treating hypertension and heart failure, regardless of renin levels 4, 6.
• The aldosterone-to-renin ratio (ARR) is a common screening test for primary aldosteronism, but medications can confound the ARR and reduce its interpretability 5.
• Eplerenone and spironolactone have been shown to be effective in reducing blood pressure and cardiovascular morbidity in patients with resistant hypertension, which may be related to high renin levels 6.
• The pharmacological treatment of aldosterone excess, including primary aldosteronism, relies on mineralocorticoid receptor antagonists, such as spironolactone and eplerenone, which can be effective in reducing aldosterone levels and blood pressure 7.

Considerations for High Renin Patients

• High renin patients may require careful monitoring of potassium levels and renal function when using aldosterone inhibitors, as these medications can increase the risk of hyperkalemia and worsening renal function 3, 6.
• The choice of aldosterone inhibitor may depend on the patient's individual characteristics, such as the presence of anti-androgenic side effects with spironolactone, and the potential benefits of eplerenone in reducing cardiovascular morbidity 4, 6.
• Further research is needed to determine the optimal treatment strategy for high renin patients with hypertension or heart failure, including the use of aldosterone inhibitors and other medications that target the renin-angiotensin-aldosterone system (RAAS) 3, 5, 7.