Mineralocorticoid receptor antagonists (MRAs) reduced the risk of cardiovascular death or heart failure hospitalisation in patients with heart failure and reduced ejection fraction (HFrEF) and also in those with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), according to new research.

The latest study, presented by Professor Pardeep Jhund at the ESC (European Society of Cardiology) Congress 2024 and simultaneously published in The Lancet, showed, for the first time, that treatment with MRAs can benefit patients with all types of heart failure and should be prescribed in suitable patients going forward.

An illustration of a heart on a blue background

Previously there was strong evidence that MRAs could improve cardiovascular outcomes in patients with heart failure and reduced ejection fraction (HFrEF), however the benefits for patients with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) were less clear. To answer these questions, this study examined the effects of MRAs using data from four trials across both types of heart failure.

This was a pre-specified, individual patient-level meta-analysis of four placebo-controlled trials: RALES (spironolactone) and EMPHASIS-HF (eplerenone), which enrolled HFrEF patients, and TOPCAT (spironolactone) and FINEARTS-HF (finerenone), which enrolled HFmrEF/HFpEF patients. The effect of MRAs was estimated for the outcomes of cardiovascular death or HF hospitalisation, components of this composite, total HF hospitalisations (with and without cardiovascular deaths) and all-cause death. An interaction between trials and treatment was tested to examine the heterogeneity of effect in the populations.

In 13,846 patients, MRAs reduced the risk of cardiovascular death or HF hospitalisation by 23%. There was also a significant interaction by trials and treatment due to the greater efficacy in HFrEF (34% reduction) compared with HFmrEF/HFpEF (13% reduction). The effects were consistent across all subgroups in the HFrEF and HFmrEF/HFpEF trials.

Significant reductions in HF hospitalisation were observed in the HFrEF trials (37% reduction) and the HFmrEF/HFpEF trials (18% reduction) The same pattern was observed for total HF hospitalisations with or without cardiovascular death. Cardiovascular death was reduced in the HFrEF trials (by 28%) but the reduction (8%) in the HFmrEF/HFpEF trials did not reach statistical significance.

The risk of hyperkalaemia was doubled with an MRA compared with placebo, but the incidence of serious hyperkalaemia (defined as a laboratory potassium >6.0 mmol/L) was low (2.9% vs. 1.4%). The risk of hypokalaemia (potassium <3.5 mmol/L) was halved (7% vs. 14%).

Professor Jhund, Professor of Cardiology and Epidemiology at the University of Glasgow’s School of Cardiovascular & Metabolic Health, said: “This analysis confirms the benefits of MRAs in patients with HF, across the spectrum of ejection fractions. Our findings indicate that treatment with an MRA may be considered in all patients with HF without a contraindication.”

The study, ‘MRAs in heart failure - An individual patient data meta-analysis of randomised trial’ is published in The Lancet.


Enquiries: ali.howard@glasgow.ac.uk or elizabeth.mcmeekin@glasgow.ac.uk

First published: 1 September 2024