Key result
Finerenone reduces CV death ~11% and worsening HF vs placebo in HFpEF and HFmrEF.
Why the study?
Direct comparative evidence evaluating the clinical outcomes and safety of finerenone versus other pharmacological agents remains limited in HFpEF or HFmrEF.
Does finerenone, SGLT2i, RASi, or ARNI improve clinical outcomes and safety compared to placebo and each other in patients with HFpEF or HFmrEF?
Meta-Analysis (n=65,929)
Does finerenone, SGLT2i, RASi, or ARNI improve clinical outcomes and safety compared to placebo and each other in patients with HFpEF or HFmrEF?
Odds Ratio: 0.89 (95% CI 0.82–0.95)
In patients with HFpEF or HFmrEF, finerenone reduces CV death and worsening HF events compared to placebo, while indirect comparisons suggest SGLT2 inhibitors like sotagliflozin and empagliflozin may offer greater reductions in total HF hospitalizations.
Finerenone reduces CV death in HFpEF/HFmrEF; extends MRA benefit beyond HFrEF while warranting renal monitoring.
Background: Although pharmacological therapies for heart failure have advanced, direct comparative evidence on the clinical outcomes and safety of finerenone versus other agents remains limited in HFpEF or HFmrEF. Objective: A network meta-analysis was conducted to compare clinical outcomes and safety among finerenone, sodium-glucose cotransporter 2 inhibitors (SGLT2i), renin-angiotensin system inhibitors (RASi) and angiotensin receptor-neprilysin inhibitors (ARNI) in patients with HFpEF or HFmrEF. Methods: A comprehensive systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science from database inception to 3 January 2026. Randomized controlled trials (RCTs) were included, and a network meta-analysis was performed to evaluate cardiovascular (CV) death, worsening heart failure (HF) events, composite renal outcomes, all-cause mortality, total HF hospitalizations, and adverse events. Results: A total of 27 RCTs involving 65,929 patients were included. Compared with placebo, finerenone was associated with lower risk of CV death (OR = 0.89, 95% CI 0.82-0.95) and worsening HF events (OR = 0.75, 95% CI 0.71-0.79), but higher risk of composite renal outcomes (OR = 1.42, 95% CI 1.10-1.84). No significant differences in CV death or all-cause mortality. In indirect comparisons, finerenone was associated with lower risk of worsening HF events versus canagliflozin (OR = 2.12, 95% CI 1.13-3.98) and RASi (OR = 1.21, 95% CI 1.03-1.42). Sotagliflozin (OR = 0.61, 95% CI 0.50-0.74) and empagliflozin (OR = 0.83, 95% CI 0.69-0.99) were associated with lower risk of total HF hospitalizations. Relative to finerenone, canagliflozin (OR = 1.53, 95% CI 1.25-1.88) and RASi (OR = 1.31, 95% CI 1.10-1.57) were associated with higher risk of adverse events. Conclusion: Compared with placebo, finerenone was associated with lower risk of CV death and worsening HF events. As most comparisons between interventions were indirect, sotagliflozin and empagliflozin were associated with lower risk of total HF hospitalizations relative to finerenone, whereas ARNI and empagliflozin were associated with lower risk of composite renal outcomes, and canagliflozin and RASi with higher risk of adverse events. No significant differences were observed between interventions for CV death or all-cause mortality.
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Fu et al. (2026) conducted a meta-analysis in Heart failure with preserved or mildly reduced ejection fraction (HFpEF or HFmrEF) (n=65,929). Finerenone vs. Placebo was evaluated on Cardiovascular death (OR 0.89, 95% CI 0.82-0.95). Finerenone reduced the risk of cardiovascular death (OR 0.89) and worsening heart failure events (OR 0.75) compared to placebo in patients with heart failure with preserved or mildly reduced ejection fraction.
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