A network meta-analysis published in the Frontiers in Pharmacology compared the efficacy and safety of finerenone, sodium-glucose cotransporter 2 inhibitors (SGLT2i), renin-angiotensin system inhibitors (RASi), and angiotensin receptor-neprilysin inhibitors (ARNI) across major cardiovascular and renal outcomes.

Investigators performed a systematic review and network meta-analysis of randomized controlled trials identified through PubMed, Embase, the Cochrane Library, and Web of Science through January 2026. The analysis included 27 randomized trials involving 65,929 patients with HFpEF or HFmrEF.

The study evaluated cardiovascular death, worsening heart failure events, composite renal outcomes, all-cause mortality, total heart failure hospitalizations, and adverse events. 

Findings

• Compared with placebo, finerenone was associated with a lower risk of cardiovascular death (OR, 0.89; 95% CI, 0.82–0.95) and worsening heart failure events (OR, 0.75; 95% CI, 0.71–0.79).
• Finerenone was associated with a higher risk of composite renal outcomes compared with placebo (OR, 1.42; 95% CI, 1.10–1.84).
• In indirect comparisons, finerenone was associated with a lower risk of worsening heart failure events than canagliflozin (OR, 2.12; 95% CI, 1.13–3.98) and RASi therapy (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 risks of total heart failure hospitalizations relative to finerenone.
• No significant differences between interventions were observed for cardiovascular death or all-cause mortality, while canagliflozin (OR, 1.53; 95% CI, 1.25–1.88) and RASi therapy (OR, 1.31; 95% CI, 1.10–1.57) were associated with higher risks of adverse events compared with finerenone.

The findings suggest that finerenone is associated with lower risks of worsening heart failure events and cardiovascular death compared with placebo in patients with HFpEF or HFmrEF.