The Pharmacological Properties and Safety Profile of Mineralocorticoid Receptor Antagonists in Heart Failure with Reduced Ejection Fraction

Among the established mineralocorticoid receptor antagonists (MRAs), spironolactone and eplerenone have demonstrated significant clinical utility in managing conditions such as chronic heart failure, resistant hypertension, and hyperaldosteronism. Spironolactone, the first steroidal MRA, is known for its broad receptor affinity, contributing to both therapeutic benefits and endocrine-related side effects. Eplerenone, a more selective agent, offers improved tolerability with reduced hormonal adverse effects. This review explores the pharmacokinetic and pharmacodynamic profiles of these agents, highlighting their mechanisms of action, receptor-binding characteristics, and clinical implications. The safety considerations associated with long-term use, particularly hyperkalemia and renal function impairment, are also discussed to provide a comprehensive understanding of their therapeutic roles.