What are the effects of eplerenone on blood pressure?

From the Guidelines

Eplerenone is effective in lowering blood pressure, particularly in patients with resistant hypertension, and is recommended as a fourth-line treatment option, with a potential dosing range of 50-200 mg, and may need to be administered twice daily due to its shorter time of action compared to spironolactone. The effects of eplerenone on blood pressure are mediated through its mechanism as a selective mineralocorticoid receptor antagonist, which prevents aldosterone from promoting sodium and water retention while increasing potassium levels, leading to decreased blood volume and reduced vascular resistance, resulting in lower blood pressure 1. According to the 2024 ESC guidelines for the management of elevated blood pressure and hypertension, eplerenone may be considered as an alternative to spironolactone in patients who do not tolerate spironolactone, and its use is supported by evidence from studies such as the EPHESUS trial, which demonstrated a 15% reduction in overall mortality and a 17% reduction in cardiovascular mortality in patients with heart failure after myocardial infarction 1. Key points to consider when using eplerenone for blood pressure management include:

• Regular monitoring of potassium levels and kidney function to prevent hyperkalemia
• Potential dosing range of 50-200 mg, with twice-daily administration due to its shorter time of action
• Eplerenone is particularly beneficial for patients with resistant hypertension, primary aldosteronism, or heart failure, where aldosterone blockade provides additional cardiovascular protection beyond blood pressure reduction
• Eplerenone causes fewer hormonal side effects such as gynecomastia compared to spironolactone due to its greater selectivity for aldosterone receptors 1.

From the FDA Drug Label

The mean placebo-subtracted reductions in trough cuff blood pressure achieved by eplerenone in these studies at doses up to 200 mg are shown in Figures 3 and 4 Patients treated with eplerenone 50 mg to 200 mg daily experienced significant decreases in sitting systolic and diastolic blood pressure at trough with differences from placebo of 6 to 13 mm Hg (systolic) and 3 to 7 mm Hg (diastolic). Blood pressure lowering was apparent within 2 weeks from the start of therapy with eplerenone, with maximal antihypertensive effects achieved within 4 weeks.

The effects of eplerenone on blood pressure are a significant decrease in both systolic and diastolic blood pressure.

• The decrease in systolic blood pressure ranges from 6 to 13 mm Hg.
• The decrease in diastolic blood pressure ranges from 3 to 7 mm Hg. The antihypertensive effects of eplerenone are apparent within 2 weeks of therapy and reach their maximum within 4 weeks 2.

From the Research

Effects of Eplerenone on Blood Pressure

• Eplerenone is an aldosterone receptor blocker that has been shown to lower blood pressure in patients with primary hypertension 3, 4, 5, 6, 7.
• The reduction in systolic blood pressure with eplerenone is approximately 9.21 mmHg, and the reduction in diastolic blood pressure is approximately 4.18 mmHg 3.
• Eplerenone has been found to be effective in lowering blood pressure in patients with mild and moderate essential hypertension, and it can be used as monotherapy or in combination with other antihypertensive agents 4, 5, 6, 7.
• The antihypertensive efficacy of eplerenone is similar to that of other antihypertensive agents, although it may have a more favorable side effect profile compared to some other agents, such as spironolactone 4, 5, 7.

Dose-Response Effect

• There may be a dose-response effect for eplerenone in the reduction of systolic blood pressure, with higher doses (up to 400 mg/day) potentially leading to greater reductions in blood pressure 3.
• However, the evidence for a dose-response effect is uncertain, and more research is needed to fully understand the relationship between eplerenone dose and blood pressure reduction 3.

Side Effects and Safety

• Eplerenone is generally well-tolerated, but it can cause hyperkalemia, particularly in patients with diabetes, proteinuria, or heart failure, or in those taking moderate CYP450 3A4 inhibitors 4, 6, 7.
• The risk of hyperkalemia with eplerenone is a concern, and patients should be closely monitored for this potential side effect 6, 7.