Differentiation between emerging non-steroidal and established steroidal mineralocorticoid receptor antagonists: head-to-head comparisons of pharmacological and clinical characteristics.

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.

• Authors: Jonatan Barrera-Chimal, Peter Kolkhof, Ixchel Lima-Posada, Alexandre Joachim, Patrick Rossignol, Frederic Jaisser
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 30 Issue 11 Pg. 1141-1157 (Nov 2021) ISSN: 1744-7658 [Electronic] England
• PMID: 34758679 (Publication Type: Comparative Study, Journal Article, Review)

Chemical References

• Mineralocorticoid Receptor Antagonists
• Steroids

Topics

• Animals
• Drug Development
• Heart Failure (drug therapy)
• Humans
• Hyperkalemia (chemically induced)
• Kidney Diseases (drug therapy)
• Mineralocorticoid Receptor Antagonists (adverse effects, pharmacology)
• Steroids (adverse effects, pharmacology)