Mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction according to body weight

Aims: Obesity is associated with excessive adipocyte-derived aldosterone secretion, independent of the classical renin–angiotensin–aldosterone cascade, and mineralocorticoid receptor antagonists (MRAs) may be more effective in obese patients with heart failure (HF) with reduced ejection fraction (HFrEF). 

Methods and results: Using individual patient-level data from two randomized placebo-controlled trials, RALES and EMPHASIS-HF, the effect of MRA treatment, compared with placebo, and outcomes were assessed according to body weight at baseline, examined both as a categorized (above/below median) and continuous variable. The primary outcome was the composite of HF hospitalization or cardiovascular death. Of the 4400 patients randomized in RALES and EMPHASIS-HF, 4386 (99.7%) participants had data on body weight at baseline. The median body weight was 75 kg (25th–75th percentile, 65–85 kg). Compared with placebo, MRA treatment reduced the risk of the primary composite outcome, each of its components, and all-cause death across body weight categories. However, the beneficial effect of MRA treatment on the primary composite outcome and HF hospitalization was larger with higher body weight, whether weight was examined as a categorized or as a continuous variable. In addition, there was a trend towards a greater benefit with MRA treatment on cardiovascular death and all-cause death with higher body weight. Similar associations were found in both men and women, and when the trials were analysed individually. 

Conclusion: In patients with HFrEF, the beneficial effect of MRA treatment on clinical outcomes appeared to be larger in individuals with higher body weight. 

Trial registration: NCT00232180.