MR Overactivation Reframes HFpEF as a Treatable Neurohormonal Continuum

This narrative review synthesizes the mechanistic and trial evidence linking mineralocorticoid receptor overactivation to heart failure with preserved ejection fraction and positions mineralocorticoid receptor antagonists and aldosterone synthase inhibitors as disease-modifying options for cardiology and anticoagulation pharmacists managing cardiorenal patients.

finerenonespironolactoneeplerenonemineralocorticoid receptor antagonistaldosterone synthase inhibitorbaxdrostatlorundrostatHFpEFheart failurehyperkalemiaFINEARTS-HFTOPCATFIDELITYreviewcardiorenal Cardiology / Anticoagulation

Background Information

Targeting mineralocorticoid receptor overactivation shows promise in HFpEF management.

Heart failure with preserved ejection fraction (HFpEF) involves multiple mechanisms, and mineralocorticoid receptor (MR) overactivation is a significant contributor. Both steroidal and non-steroidal mineralocorticoid receptor antagonists (MRAs) show promise in reducing heart failure events and cardiovascular death in HFpEF. MR overactivation is a key target in HFpEF, and early intervention with MRAs may prevent or slow disease progression. Further research on MR modulators is warranted. Targeting MR overactivation offers a promising strategy for preventing and treating HFpEF.

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Authors: Kobayashi M, Pitt B, Zannad F

Citation: Kobayashi M, Pitt B, Zannad F Mineralocorticoid receptor overactivation in heart failure with preserved ejection fraction. European heart journal. 2026. doi:10.1093/eurheartj/ehag578

Article Links: PubMed · Journal / DOI

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