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

Abstract : 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, with a low 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 MRA, and biomarkers that are predictive of MRA response need to be identified and validated.
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https://hal.univ-lorraine.fr/hal-03429407
Contributor : Erwan BOZEC Connect in order to contact the contributor
Submitted on : Monday, November 15, 2021 - 4:00:50 PM
Last modification on : Wednesday, September 28, 2022 - 4:20:12 PM
Long-term archiving on: : Wednesday, February 16, 2022 - 9:01:22 PM

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Jonatan Barrera-Chimal, Peter Kolkhof, Ixchel Lima-Posada, Alexandre Joachim, Patrick Rossignol, et al.. Differentiation between emerging non-steroidal and established steroidal mineralocorticoid receptor antagonists: head-to-head comparisons of pharmacological and clinical characteristics. Expert Opinion on Investigational Drugs, 2021, ⟨10.1080/13543784.2021.2002844⟩. ⟨hal-03429407⟩

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