Mineralocorticoid Antagonism in Heart Failure: Established and Emerging Therapeutic Role

The pathophysiology of heart failure (HF) is related to the overactivation of the mineralocorticoid receptor (MR), leading to fluid retention and adverse myocardial remodeling. While mineralocorticoid receptor antagonists (MRAs) are recommended for the treatment of HF with reduced ejection fraction (HFrEF), they remain underused due to adverse effects like hyperkalemia; and their efficacy is controversial in HF with mildly reduced ejection fraction (HFmrEF) and HF with preserved ejection fraction (HFpEF). Recent trials in people with diabetes and kidney disease have supported the use of nonsteroidal MRAs in reducing HF related morbidity and mortality and have less side effects than their steroidal counterparts. The efficacy and safety of non-steroidal MRAs have not been tested in HF and are currently being evaluated in additional clinical trials. This review comprehensively examines the current data regarding MRAs for HF and the future direction of nonsteroidal MRA research while exploring the causes of MRA underutilization.