Abstract Body (Do not enter title and authors here): Background: Liver fibrosis is increasingly recognized as a comorbidity in heart failure (HF), driven by venous congestion, hypoperfusion, systemic inflammation, and metabolic disturbances. The fibrosis-4 (FIB-4) index is an established non-invasive test used to evaluate liver fibrosis.
Research Questions: What is the prognostic value of the FIB-4 index in patients with heart failure and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF).
Methods: We analysed data from FINEARTS-HF, a phase 3, randomized, placebo-controlled trial evaluating the efficacy and safety of finerenone in patients with HFmrEF/HFpEF. The FIB-4 index was calculated using the formula: (age [years] × AST [U/L])/(platelets [109/L] × sqrt [ALT] [U/L]). Patients were grouped based on the risk of progressive fibrosis determined using the FIB-4 index: low (<1.30), indeterminate (1.30–2.67), and high (>2.67) risk (with a cutoff of 2.0 for those aged >65 years). Outcomes were examined using semiparametric proportional rates models for total events and Cox models for time-to-first-event data, stratified by region, and LVEF (<60%, ≥60%).
Results: Of 6001 randomised patients, 5476 (91.3%) had baseline FIB-4 index: 3166 (57.8%) were low risk, 1433 (26.2%) indeterminate, and 877 (16.0%) high risk. Compared with low risk of progressive fibrosis, patients with high risk were older, more often male and Asian, and more likely to have atrial fibrillation, prior stroke, higher N-terminal pro B-type natriuretic peptide (NT-proBNP), and worse kidney function. A higher FIB-4 index was associated with greater risk of the primary endpoint (cardiovascular death and total worsening heart failure events), its components, and similarly, all-cause death (Figure). Finerenone, compared with placebo, reduced the risk of the primary endpoint across all FIB-4 index groups: low risk: RR: 0.73 (95% CI: 0.61-0.88); indeterminate: 0.91 (95% CI: 0.69-1.19); high risk: 0.80 (95% CI: 0.61-1.07). The benefit of finerenone was not modified by FIB-4 index (P_interaction = 0.38).
Conclusions: FIB-4, potentially reflecting liver fibrosis, independently predicts the risk of HF events in HFmrEF/HFpEF. Finerenone consistently reduced HF events across the low, indeterminate, and high FIB-4 index.