Finerenone, eplerenone, and spironolactone in heart failure with preserved ejection fraction: a Bayesian network meta-analysis of efficacy and safety

AIMS: The comparative effects of mineralocorticoid receptor antagonists (MRAs) in heart failure with preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF) remain uncertain, including potential differences between steroidal MRAs and finerenone. This Bayesian network meta-analysis aimed to compare the efficacy and safety of finerenone, eplerenone, and spironolactone vs placebo in HFpEF/HFmrEF. METHODS: We searched Pubmed, Cochrane, and Embase for studies focused on MRA treatment in HFpEF and/or HFmrEF. Eight randomized controlled trials enrolling adults with HFpEF or HFmrEF (LVEF ≥40%) were analysed in a fixed-effects Bayesian network meta-analysis. Risk ratios (RRs) with 95% credible intervals (CrIs) were estimated for hospitalization for HF, cardiovascular death, and hyperkalaemia. Heterogeneity was assessed using I2. RESULTS: Across a network comprising 10 644 patients, mean age 70.2; 48% women; mean LVEF 54.9%, finerenone reduced hospitalization for HF vs placebo (RR 0.84; 95% CrI 0.75-0.93), whereas spironolactone (RR 0.86; 95% CrI 0.73-1.01) and eplerenone (RR 0.86; 95% CrI 0.59-1.26) showed non-significant effects. None of the MRAs achieved a statistically significant reduction in cardiovascular mortality vs placebo: finerenone (RR 0.93; 95% CrI 0.78-1.10), spironolactone (RR 0.93; 95% CrI 0.76-1.14), and eplerenone (RR 1.10; 95% CrI 0.29-5.69). All MRAs increased hyperkalaemia vs placebo: finerenone (RR 2.06; 95% CrI 1.77-2.41), spironolactone (RR 2.13; 95% CrI 1.81-2.53), and eplerenone (RR 2.17; 95% CrI 0.75-7.97). CONCLUSION: In HFpEF/HFmrEF, finerenone was the only MRA to significantly reduce hospitalization for HF, while no agent significantly reduced cardiovascular mortality and hyperkalaemia risk increased across therapies. Overall, finerenone may offer the most favourable efficacy-safety balance among MRAs, pending confirmation in larger dedicated trials.