Mineralocorticoid receptor antagonists benefit heart failure patients across all ejection fractions

Mineralocorticoid receptor antagonists (MRAs) reduced the risk of cardiovascular death or hospitalisation for heart failure (HF) in patients with HF and reduced ejection fraction (HFrEF) and in patients with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), according to new research presented today in a Hotline session at the ESC Congress 2024.

There is strong evidence for the use of MRAs to improve cardiovascular outcomes in patients with HFrEF, but their benefit in patients with HFmrEF/HFpEF is less clear. We examined the effects of MRAs using data from four studies in both types of HF.”

Professor Pardeep Jhund, Academic Officer, University of Glasgow, UK

This was a pre-specified, individual patient-level meta-analysis of four placebo-controlled trials: RALES (spironolactone) and EMPHASIS-HF (eplerenone) involving HFrEF patients, and TOPCAT (spironolactone) and FINEARTS-HF (finerenone) involving HFmrEF/HFpEF patients. The effect of MRAs was estimated for the outcomes of cardiovascular death or HF hospitalization, components of this composite, total HF hospitalizations (including and excluding cardiovascular deaths), and all-cause death. A study-by-treatment interaction was tested to examine heterogeneity of effect across populations.

In 13,846 patients, MRAs reduced the risk of cardiovascular death or HF-related hospitalization (hazard ratio [HR]; 0.77; 95% confidence interval [CI] 0.72–0.83). There was a significant study-by-treatment interaction (p for interaction = 0.0012) due to greater efficacy in HFrEF (HR 0.66; 95% CI 0.59–0.73) compared with HFmrEF/HFpEF (HR 0.87; 95% CI 0.79–0.95). The effects were consistent across all subgroups of the HFrEF and HFmrEF/HFpEF studies.

Significant reductions in HF-related hospitalizations were observed in the HFrEF trials (HR 0.63; 95% CI 0.55-0.72) and the HFmrEF/HFpEF trials (HR 0.82; 95% CI 0.74-0.91). The same pattern was observed for the total number of HF-related hospitalizations with or without cardiovascular death. Cardiovascular death was reduced in the HFrEF trials (HR 0.72; 95% CI 0.63-0.82) but not in the HFmrEF/HFpEF trials (HR 0.92; 95% CI 0.80-1.05).

The risk of hyperkalemia was twice as high with MRA compared with placebo, but the incidence of severe hyperkalemia (potassium > 6.0 mmol/l) was low (2.9% versus 1.4%). The risk of hypokalemia (potassium

“This analysis confirms the benefit of MRAs in patients with HF across the spectrum of ejection fractions. Our findings suggest that treatment with an MRA can be considered in all patients with HF without contraindication,” concluded Professor Jhund.