Comparative clinical outcomes and safety of finerenone, SGLT2 inhibitors, RAS inhibitors and ARNI in heart failure with preserved or mildly reduced ejection fraction: a systematic review and network meta-analysis
Abstract
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…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 65,929 participants or records.
Read the paper
Related studies
- Strategy for Mitigating DKA Risk in Patients with Type 1 Diabetes on Adjunctive Treatment with SGLT Inhibitors: A STICH Protocol
- Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance
- SGLT2 Inhibitors in Heart Failure: Targeted Metabolomics and Energetic Metabolism
- Mechanisms of blood pressure reduction with sodium-glucose co-transporter 2 (SGLT2) inhibitors
- Sodium-glucose cotransporter inhibitors: beyond glycaemic control
- Decoding the effects of SGLT2 inhibitors on cardiac arrhythmias in heart failure
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.