Novel non-steroidal mineralocorticoid receptor antagonists in cardiorenal disease

Abstract

Mineralocorticoid receptor antagonists (MRAs) are key agents in guideline-oriented drug therapy for cardiovascular diseases such as chronic heart failure with reduced ejection fraction and resistant hypertension. Currently available steroidal MRAs are efficacious in reducing morbidity and mortality; however, they can be associated with intolerable side effects including hyperkalaemia in everyday clinical practice. Recently, a new class of non-steroidal MRAs (including esaxerenone, AZD9977, apararenone, KBP-5074 and finerenone) have been developed with an improved benefit-risk profile and a novel indication for finerenone for diabetic kidney disease. To better understand the non-steroidal MRAs, this review provides information on the molecular pharmacology as well as relevant current preclinical and clinical data on cardiorenal outcomes. A comparative review of all compounds in the class is discussed with regard to clinical efficacy and safety as well as a perspective outlining their future use in clinical practice. LINKED ARTICLES: This article is part of a themed issue on Emerging Fields for Therapeutic Targeting of the Aldosterone-Mineralocorticoid Receptor Signaling Pathway. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc.

Keywords: aldosterone; antagonist; cardiovascular disease; diabetic kidney disease; mineralocorticoid receptor; nonsteroidal.