From the Guidelines
Eplerenone has a significant advantage over spironolactone in causing less gynaecomastia and erectile dysfunction in men, making it a preferable choice for patients who experience these side effects. This is due to its selective mechanism of action, which blocks mineralocorticoid receptors without significant binding to androgen or progesterone receptors 1. The most recent guidelines from the European Heart Journal, published in 2024, support the use of eplerenone as an alternative to spironolactone, especially in patients with primary aldosteronism, due to its reduced risk of endocrine side effects 1.
Some of the key benefits of eplerenone over spironolactone include:
- Reduced risk of gynaecomastia and erectile dysfunction in men
- Lower risk of menstrual irregularities in women
- Fewer drug interactions compared to spironolactone
- Selective blockade of mineralocorticoid receptors without significant binding to androgen or progesterone receptors
However, it's essential to consider the trade-offs, including:
- Eplerenone is generally more expensive than spironolactone
- Requires twice-daily dosing, compared to once-daily for spironolactone
- May be less potent at equivalent doses
The 2024 ESC guidelines for the management of elevated blood pressure and hypertension provide the most up-to-date and high-quality evidence for the use of eplerenone in primary aldosteronism, supporting its advantage over spironolactone in terms of reduced endocrine side effects 1. In contrast, older studies, such as the 2001 guidelines for the diagnosis and treatment of chronic heart failure, although relevant, do not provide the same level of evidence as the more recent guidelines 1.
From the Research
Advantages of Eplerenone over Spironolactone
- Eplerenone is a more selective blocker of the mineralocorticoid receptor than spironolactone, which results in fewer antiandrogenic side-effects 2, 3, 4.
- The selective nature of eplerenone leads to a lower incidence of male gynaecomastia and female mastodynia compared to spironolactone 2, 3, 4.
- Eplerenone has a similar antihypertensive efficacy to other antihypertensive agents and has demonstrated renoprotective effects in diabetic patients with hypertension 4.
- Eplerenone is generally well tolerated, although hyperkalemia is a concern, and its administration with potent inhibitors of CYP3A4 is contraindicated due to the risk of hyperkalemia 4.
Comparison of Efficacy and Safety
- Studies have shown that spironolactone has a greater antihypertensive effect than eplerenone in patients with hypertension associated with primary aldosteronism 2.
- However, eplerenone is considered a safer alternative to spironolactone, especially for patients who develop anti-androgenic side effects such as breast tenderness, gynecomastia/mastodynia, and/or sexual dysfunction 5, 3.
- Both eplerenone and spironolactone appear to have pleiotropic effects that confer cardioprotection and renoprotection beyond their antihypertensive effect, but the weight of evidence regarding efficacy is currently in favor of spironolactone 5.