MRAs in Elderly Heart Failure Patients

Study Questions:

What is the effect of mineralocorticoid receptor antagonist (MRA) treatment (vs. placebo) in older patients (≥75 years of age) compared with younger patients (<75 years of age) with heart failure (HF)?


The study authors conducted an individual patient data meta-analysis of RALES, EMPAHSIS-HF, and TOPCAT trials using Cox proportional hazards models stratified by trial. The final study cohort was comprised of 1,756 patients (853 randomized to placebo and 903 to MRA) ≥75 years of age, along with 4,411 patients (2,242 randomized to placebo and 2,169 to MRA) <75 years of age. For consistency across trials, the primary outcome was a composite of cardiovascular death or HF hospitalization in the present analysis. The authors also assessed cardiovascular death alone and all-cause death.


The number of patients, ≥75 years of age, in the RALES study was 352 (21%), 657 (24%) in the EMPHASIS-HF study, and 747 (42%) in the TOPCAT-Americas study. The treatment groups were well balanced. Of patients ≥75 years of age and those 80 years of age, 61% were male, 30% had diabetes, and the mean estimated glomerular filtration rate was 59 ml/min. The primary outcome occurred in 331 patients (38.8%) in the placebo group versus 281 (31.1%) in the MRA group (hazard ratio, 0.74; 95% confidence interval, 0.63-0.86; p < 0.001; and the heterogeneity p value [heterogeneity p = Cochran’s Q p value of treatment effect by study interaction] was 0.52). Cardiovascular death and all-cause death were also reduced by MRAs without significant between-trial or age (younger vs. older) heterogeneity. The absolute event reduction and number needed to treat to benefit were also similar between younger and older patients and ranged from 8 to 31 patients for the primary composite outcome of cardiovascular or HF hospitalization. Worsening renal function and hyperkalemia occurred more frequently in patients taking MRAs (vs. placebo). Compared to younger patients, worsening renal function (but not hyperkalemia) was found more frequently in the elderly.


The study authors concluded that MRAs reduced morbidity and mortality in elderly patients with HF, a beneficial effect that is more marked in patients with HFrEF but homogenous across HFrEF and HFpEF. They also concluded that implementation of measures that increase MRA treatment in this population is warranted.


This is an important study because it suggests that aldosterone receptor blockade reduces both morbidity and mortality in the elderly HF patients. Given the propensity for azotemia, with MRAs, it is important to initiate therapy only in those with relatively preserved renal function. Also, close monitoring of renal function is warranted once therapy is initiated.

Clinical Topics: Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure

Keywords: Azotemia, Diabetes Mellitus, Geriatrics, Glomerular Filtration Rate, Heart Failure, Hospitalization, Hyperkalemia, Mineralocorticoid Receptor Antagonists, Receptors, Mineralocorticoid, Respiratory Sounds, Secondary Prevention

< Back to Listings