MRAs and Race in Heart Failure: An Individual Participant Data Meta-Analysis of Randomized Trials

There are concerns that renin-angiotensin system inhibitors are less effective in Black patients than non-Black patients with heart failure (HF). We examined the efficacy and safety of mineralocorticoid-receptor antagonists (MRAs), compared with placebo, in patients with HF with reduced ejection fraction or HF with mildly reduced/preserved ejection fraction, according to self-reported race (Black or non-Black).

This was a post hoc individual participant data meta-analysis of the 4 large placebo-controlled trials comparing MRAs to placebo in patients with HF with reduced ejection fraction (RALES [Randomized Aldactone Evaluation Study], EMPHASIS-HF [Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure]) and HF with mildly reduced/preserved ejection fraction (TOPCAT [Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist], FINEARTS-HF [Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure]). The primary outcome was a composite of cardiovascular death or first HF hospitalization.

Of the 13 846 patients randomized in the 4 trials, 577 (4.2%) identified as Black. Despite being younger (64 versus 70 years), rates of HF hospitalizations and death were higher in Black than non-Black patients. The hazard ratio for MRA versus placebo for the primary composite outcome was 0.87 (95% CI, 0.66-1.15) in Black patients and 0.77 (95% CI, 0.72-0.82) in non-Black patients (P_interaction=0.34), with 3.9 and 2.7 fewer events per 100 person-years of treatment, respectively. For first HF hospitalization, the hazard ratios were 0.86 (95% CI, 0.63-1.17) and 0.73 (95% CI, 0.68-0.80) for Black and non-Black patients, respectively (P_interaction=0.36). The corresponding hazard ratios for cardiovascular death were 0.75 (95% CI, 0.48-1.17) and 0.81 (95% CI, 0.74-0.90), respectively (P_interaction=0.80). Adverse events with MRAs, compared with placebo, were not modified by race. The effects of MRAs in patients with HF with reduced ejection fraction and HF with preserved ejection fraction, individually, were not modified by race.

There was no statistically significant evidence of heterogeneity in the absolute or relative effects of MRAs on clinical outcomes between Black and non-Black patients with HF, regardless of HF phenotype.