Finerenone in patients with chronic kidney disease and type 2 diabetes with and without heart failure: a prespecified subgroup analysis of the FIDELIO-DKD trial

Abstract

Aims: This prespecified analysis of the FIDELIO-DKD trial compared the effects of finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, on cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) by history of heart failure (HF).

Methods and results: Patients with T2D and CKD (urine albumin-to-creatinine ratio ≥30-5000 mg/g and estimated glomerular filtration rate [eGFR] ≥25-<75 ml/min/1.73 m² ), without symptomatic HF with reduced ejection fraction (New York Heart Association II-IV) and treated with optimized renin-angiotensin system blockade were randomized to finerenone or placebo. The composite cardiovascular (CV) outcome (CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for HF) and composite kidney outcome (kidney failure, sustained ≥40% decrease in eGFR from baseline, or renal death) were analysed by investigator-reported medical history of HF. Of 5674 patients, 436 (7.7%) had a history of HF. Over a median follow-up of 2.6 years, the effect of finerenone compared with placebo on the composite CV outcome was consistent in patients with and without a history of HF (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.50-1.06 and HR 0.90, 95% CI 0.77-1.04, respectively; interaction p = 0.33). The effect of finerenone on the composite kidney outcome did not differ by history of HF (HR 0.79, 95% CI 0.52-1.20 and HR 0.83, 95% CI 0.73-0.94, respectively; interaction p = 0.83).

Conclusion: In FIDELIO-DKD, finerenone improved cardiorenal outcome in patients with CKD and T2D irrespective of baseline HF history.

Keywords: Aldosterone; Chronic kidney disease; Diabetes; Finerenone; Heart failure; Mineralocorticoid receptor antagonists.

Figure 1

Composite cardiovascular outcome by history of heart failure at baseline. Incidence of the composite cardiovascular outcome was assessed in a time‐to‐event analysis. The Kaplan–Meier curves show the cumulative incidence of cardiovascular events tended to be lower with finerenone versus placebo in patients with (A) and without (B) a history of heart failure at baseline. CI, confidence interval; HR, hazard ratio.

Figure 2

Summary of CV, kidney, and HF outcomes in the total study population and by history of HF at baseline. Stratified Cox proportional hazards models were used to analyse the effects of finerenone versus placebo on CV, kidney and HF outcomes, and the forest plot shows that the effects of finerenone were not modified by history of HF at baseline. CI, confidence interval; CV, cardiovascular; HF, heart failure; HHF, hospitalization for heart failure; PY, patient‐years.

Figure 3

Time to cardiovascular death or hospitalization for heart failure in the total study population. Incidence of cardiovascular death or hospitalization for heart failure was assessed in a time‐to‐event analysis. The Kaplan–Meier curves show that the cumulative incidence of cardiovascular death or hospitalization for heart failure as first event. CI, confidence interval; HR, hazard ratio.