The following is a summary of “Steroidal MRA Across the Spectrum of Renal Function: A Pooled Analysis of RCTs” published in the November 2022 issue of Heart Failure by Ferreira et al.
It is unclear if mineralocorticoid receptor antagonists (MRAs) are effective for people with chronic kidney disease (CKD), and are underutilized in patients with renal failure. This research aimed to examine the effectiveness and safety of steroidal MRAs in randomized controlled trials over a range of estimated glomerular filtration rates (eGFRs). Patients from the EPHESUS (Eplerenone Post-AMI Heart Failure Efficacy and Survival Study), TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist in the Americas), and RALES (Randomized Aldactone Evaluation Study) trials were included in the study.
Cox models stratified by trial with treatment-by-eGFR interaction terms were used to conduct a meta-analysis of individual patient data. The creatinine formula from the Chronic Kidney Disease Epidemiology Collaboration was used to recalculate eGFR. Included in the study were 12,700 individuals, 3.31 of whom (2.6%; mean eGFR: 26.8±3.2 mL/min/1.73m2: ) had an eGFR 30 mL/min/1.73 m2. In individuals with eGFR≤30, the placebo event rate for the composite of cardiovascular death or HF hospitalization was 3-fold greater than in those with eGFR >90 mL/min/1.73 m2: 41.6 vs. 14.6 events per 100 person-years. The composite of CV death and HF hospitalization was lowered by MRAs (vs. placebo), although this effect was attenuated by decreasing eGFR.
Health-related risks (HRs) were calculated according to eGFR categories as follows: HR for >90 mL/min/1.73 m2 was 0.62 (95% CI: 0.49-0.78); HR for 61-90 mL/min/1.73 m2 was 0.69 (95% CI: 0.61-0.77); HR for 46-60 mL/min/1.73 m2 was 0.84 (95% CI: 0.74-0.95); HR for 31- Hyperkalemia was more common with decreasing eGFR (treatment-by-eGFR interaction P for trend =0.002) and was reported 2- to 3-fold more frequently among MRA users. As eGFR increased, hospitalizations and deaths from HF decreased when steroidal MRAs were used. However, their usage may be constrained in individuals with lower eGFR, especially those with values ≤30 mL/min/1.73 m2, due to diminishing effectiveness and decreasing safety.