Abstract 4361672: Race does not influence the efficacy and safety of mineralocorticoid-receptor antagonists in heart failure: An individual-participant data meta-analysis of 4 trials

Abstract

Introduction: There are concerns that renin-angiotensin system inhibitors are less effective in Black patients than non-Black patients with heart failure (HF). We have tested whether this concern might also apply to mineralocorticoid-receptor antagonists (MRAs). Objectives: We examined the efficacy and safety of MRAs, compared with placebo, in patients with HF and reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF), according to race (Black or non-Black). Methods: We conducted an individual-participant data meta-analysis of the 4 major randomized controlled trials comparing MRAs to placebo in patients with HFrEF (RALES, EMPHASIS-HF) and HFpEF (TOPCAT, FINEARTS-HF). Race was self-reported. The primary outcome was a composite of cardiovascular death or first HF hospitalization. Results: Of the 13,846 patients randomized in the four trials, 577 (4.2%) identified as Black (4.3% in the HFrEF trials; 4.1% in the HFpEF trials). Rates of HF hospitalizations and death were higher in Black than non-Black patients. The hazard ratio (HR) 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) (Figure) . For first HF hospitalization, the HRs 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 HRs 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). For cardiovascular death and total HF hospitalizations, the corresponding rate ratios were 0.80 (0.61-1.06) and 0.76 (95% CI, 0.71-0.82), respectively (P interaction =0.96). Adverse events with MRAs, compared with placebo, including hypotension, elevated creatinine, hyperkalemia, and hypokalemia were not modified by race. Findings were similar when the population was restricted to patients randomized in the Americas only. The effects of MRAs in patients with HFrEF and HFpEF, individually, were not modified by race (Figure) . Conclusions: The beneficial effects of MRAs, compared with placebo, on clinical events were comparable in Black and non-Black patients with HF, regardless of HF phenotype.