Eplerenone: The Multifaceted Drug in Cardiovascular Pharmacology

Abstract

Conventionally, rennin-angiotensin-aldosterone system (RAAS) inhibition has focused on angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers and angiotensin receptor-neprilysin inhibitors (ARNI) are the latest addition to this armamentarium. However, mineralocorticoid receptor antagonists (MRAs) also constitute an integral part of this anti-RAAS brigade, which are perceived more often as diuretics and are often under prescribed in heart failure (HF) despite being universally advocated by all major guidelines. Apart from HF, they have also shown promise in the management of hypertension, post-myocardial infarction, and hyperaldosteronism. Eplerenone, Food and Drug Administration (FDA) approved in 2002, is an acceptable alternative to spironolactone due to its sparing androgenic effects. In two big pivotal trials in heart failure (EMPHASIS -HF) and post-myocardial infarction (EPHESUS), the drug has firmly shown a reduction in adverse cardiovascular events. It has an established place in the management of resistant hypertension too. In this article, we will discuss the role of RAAS and its pathophysiology, pitfalls of spironolactone, which led to success of its congener, eplerenone, major studies conducted on eplerenone, current role of eplerenone, and comparison of the two MRAs.

Keywords: Eplerenone; gynecomastia; heart failure; hyperkalemia; mineralocorticoid receptor antagonist; resistant hypertension.

Figure 1

Heart failure syndrome resulting from angiotensin II: the key product of RAAS cascade. HF = heart failure, AT = angiotensin, SNS = sympathetic nervous system, ANP = atrial natriuretic peptide, BNP = brain natriuretic peptide

Figure 2

Pitfalls of spironolactone. HbA1C = glycosylated hemoglobin

Figure 3

Advantages and disadvantages of eplerenone. CYP3A4 = cytochrome P450 3A4 enzyme

Figure 4

Potential contraindications and cautions for eplerenone use in clinical practice. NSAID = nonsteroidal anti-inflammatory drugs

Figure 5

Outline of management of hyperkalemia in patients on MRA. MRA = mineralocorticoid receptor antagonist