efficacy and safety of mineralocorticoid receptor antagonists across geographical regions in heart failure: a patient-level pooled analysis

Background

Clinical characteristics and prognosis of patients with heart failure (HF) vary across geographic regions, which may lead to regional differences in response to pharmacological therapies.

Purpose

To evaluate the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) in patients with HF across geographic regions.

Methods

We performed a patient-level pooled analysis of the RALES (spironolactone vs placebo) and EMPHASIS-HF (eplerenone vs placebo) trials in patients with heart failure with reduced ejection fraction (HFrEF), as well as the TOPCAT-America (spironolactone vs placebo) and FINEARTS-HF (finerenone vs placebo) trials in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). The primary outcome was a composite of first HF hospitalization or cardiovascular death.

Results

Among 12,168 patients included in the analysis, 6,893 (56.6%) were from Europe, 2,310 (19.0%) from North America, 1,462 (12.0%) from Latin America, and 1,503 (12.4%) from the Asia–Pacific region. Baseline patient characteristics, including demographics, comorbidities, HF severity, and pharmacological therapies, differed across geographic regions, e.g. the youngest mean age and lowest prevalence of AF occurred in Latin America whereas the highest BMI and highest prevalence of diabetes were observed in North America. Similarly, rates of the primary composite outcome and all-cause mortality differed substantially by geographical region, with greater variation among patients with HFrEF compared to those with HFmrEF/HFpEF (Figure).

However, the effect of MRAs on the primary outcome was not modified by geographic region (hazard ratio [HR] for MRA vs placebo in all HF patients: Europe 0.77 [95% CI, 0.70–0.84], North America 0.81 [95% CI, 0.69–0.94], Latin America 0.67 [95% CI, 0.55–0.82], Asia–Pacific 0.84 [95% CI, 0.68–1.02]; P for interaction = 0.35). These findings were consistent when analyses were stratified by HF phenotype (HFrEF: P for interaction = 0.76; HFmrEF/HFpEF: P for interaction = 0.27). Similar results were observed for each component of the primary outcome and all-cause death in the overall population as well as within HF phenotype subgroups. The incidence of adverse events was comparable across geographic regions.

Conclusions

Despite substantial regional differences in patient characteristics, background therapies, and outcome rates, the efficacy and safety of MRAs were consistent across geographic regions in patients with HF.For image description, please refer to the figure legend and surrounding text.