Eplerenone: The multifaceted drug in cardiovascular pharmacology

Abstract

A BSTRACT 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.

ARNI versus ACEI/ARB in Reducing Cardiovascular Outcomes after Myocardial Infarction

“…Conventionally, RAAS inhibition has focused on clinical utilization of ACEI and ARB, and recently, ARNI brings the latest addition to this armamentarium. 8 …”

“…SNS augments RAAS activity, while natriuretic peptides‐atrial natriuretic peptide and brain natriuretic peptide antagonize the RAAS and SNS by natriuresis and vasodilation. Conventionally, RAAS inhibition has focused on clinical utilization of ACEI and ARB, and recently, ARNI brings the latest addition to this armamentarium 8 …”

“…Conventionally, RAAS inhibition has focused on clinical utilization of ACEI and ARB, and recently, ARNI brings the latest addition to this armamentarium. 8 Sacubitril/valsartan is a first-in-class angiotensin receptorneprilysin inhibitor combining the valsartan with sacubitril, a neprilysin inhibitor. In the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, ARNI therapy significantly reduced the risk of death and hospitalization for worsening HF compared with enalapril.…”

Eplerenone add-on treatment in resistant hypertension in peritoneal dialysis patient. A case report

“…Eplerenone is especially indicated in patients with left ventricular ejection fraction (EF) ≤ 40% and clinical symptoms of heart failure secondary to myocardial infarction. In two crucial clinical trials in patients with reduced EF (EPHESUS Study and EPHASIS-HF), eplerenone led to a reduction in cardiovascular mortality [20]. Eplerenone was revealed to be effective in RH patients.…”

DNA Methylation of the Angiotensinogen Gene, AGT, and the Aldosterone Synthase Gene, CYP11B2 in Cardiovascular Diseases

“…Patients with primary aldosteronism, have a higher incidence of myocardial infarction and stroke than do patients with essential hypertension [ 18 , 19 , 20 , 21 , 22 , 23 ]. Mineralocorticoid receptor antagonists (MRAs) have been shown to be effective in reducing the mortality and hospitalizations for heart failure (HF) in patients with chronic HF with a reduced left-ventricular ejection fraction (rEF) [ 24 , 25 ], and in patients with HFrEF early postmyocardial infarction [ 26 , 27 , 28 ]. Experimental animal data support a role for aldosterone in mediating cardiovascular and renal injuries.…”