Differentiation between emerging non-steroidal and established steroidal mineralocorticoid receptor antagonists: head-to-head comparisons of pharmacological and clinical characteristics. (2nd November 2021)

• Record Type: Journal Article
• Authors: Barrera-Chimal, Jonatan; Kolkhof, Peter; Lima-Posada, Ixchel; Alexandre, Joachim; Rossignol, Patrick; Jaisser, Frederic
• Is Part Of: Expert opinion on investigational drugs. Volume 30:Number 11(2021)
• Page Start: 1141
• Page End: 1157
• Publication Date: 2021-11-02
• Subjects: AZD9977 -- cardiorenal disease -- chronic kidney disease -- esaxerenone -- finerenone -- heart failure -- hypertension -- KBP-5074 -- non-steroidal mineralocorticoid receptor antagonists; Drugs -- Design -- Periodicals; Drugs, Investigational -- Bibliography; Drugs, Investigational -- Periodicals; 615.1
• DOI: 10.1080/13543784.2021.2002844
• Languages: English
• ISSNs: 1354-3784

Abstract

ABSTRACT: Introduction: Mineralocorticoid receptor (MR) antagonists (MRAs) provide cardiorenal protection. However steroidal MRAs might induce hyperkalemia and sex hormone-related adverse effects. Several novel non-steroidal MRAs are being developed that are highly selective for the MR and may have an improved safety profile. Areas covered: This narrative review summarizes data from head-to-head comparisons of emerging non-steroidal MRAs with older steroidal MRAs, including pharmacological characteristics, pharmacokinetic properties, clinical outcomes, and safety, and highlights similarities and differences between emerging agents and established steroidal MRAs. Expert opinion: Head-to-head comparisons in phase 2 trials suggest that the new non-steroidal MRAs exhibit at least equivalent efficacy to steroidal MRAs but may have a better safety profile in patients with heart failure and/or kidney disease. When also taking into account data from recent phase 3 placebo-controlled trials, these novel non-steroidal MRAs have the potential to provide a cardiorenal benefit above that of current optimized standard-of-care treatment in a high-risk population with reduced renal function, and with a lower risk of hyperkalemia. To optimize therapy, further research is needed to clarify the molecular differences in the mode of action of non-steroidal MRAs versus steroidal MRAs, and biomarkers that are predictive of MRA response need to be identified and validated.