Finerenone Reduces Risk of Incident Heart Failure in Patients With Chronic Kidney Disease and Type 2 Diabetes: Analyses From the FIGARO-DKD Trial

Abstract

Background: Chronic kidney disease and type 2 diabetes are independently associated with heart failure (HF), a leading cause of morbidity and mortality. In the FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) and FIGARO-DKD (Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease) trials, finerenone (a selective, nonsteroidal mineralocorticoid receptor antagonist) improved cardiovascular outcomes in patients with albuminuric chronic kidney disease and type 2 diabetes. These prespecified analyses from FIGARO-DKD assessed the effect of finerenone on clinically important HF outcomes.

Methods: Patients with type 2 diabetes and albuminuric chronic kidney disease (urine albumin-to-creatinine ratio ≥30 to <300 mg/g and estimated glomerular filtration rate ≥25 to ≤90 mL per min per 1.73 m2, or urine albumin-to-creatinine ratio ≥300 to ≤5000 mg/g and estimated glomerular filtration rate ≥60 mL per min per 1.73 m2), without symptomatic HF with reduced ejection fraction, were randomized to finerenone or placebo. Time-to-first-event outcomes included new-onset HF (first hospitalization for HF [HHF] in patients without a history of HF at baseline); cardiovascular death or first HHF; HF-related death or first HHF; first HHF; cardiovascular death or total (first or recurrent) HHF; HF-related death or total HHF; and total HHF. Outcomes were evaluated in the overall population and in prespecified subgroups categorized by baseline HF history (as reported by the investigators).

Results: Overall, 7352 patients were included in these analyses; 571 (7.8%) had a history of HF at baseline. New-onset HF was significantly reduced with finerenone versus placebo (1.9% versus 2.8%; hazard ratio [HR], 0.68 [95% CI, 0.50-0.93]; P=0.0162). In the overall population, the incidences of all HF outcomes analyzed were significantly lower with finerenone than placebo, including an 18% lower risk of cardiovascular death or first HHF (HR, 0.82 [95% CI, 0.70-0.95]; P=0.011), a 29% lower risk of first HHF (HR, 0.71 [95% CI, 0.56-0.90]; P=0.0043) and a 30% lower rate of total HHF (rate ratio, 0.70 [95% CI, 0.52-0.94]). The effects of finerenone on improving HF outcomes were not modified by a history of HF. The incidence of treatment-emergent adverse events was balanced between treatment groups.

Conclusions: The results from these FIGARO-DKD analyses demonstrate that finerenone reduces new-onset HF and improves other HF outcomes in patients with chronic kidney disease and type 2 diabetes, irrespective of a history of HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02545049.

Keywords: aldosterone; chronic kidney disease; finerenone; heart failure; mineralocorticoid receptor antagonist; type 2 diabetes.

Figures

Figure 1.

Kaplan-Meier estimate of time to new-onset HF (first hospitalization for HF in patients without a history of HF at baseline). HF indicates heart failure.

Figure 2.

Time to HF-related outcomes.A, Kaplan-Meier estimates for time to cardiovascular death or first HHF in the overall population. B, Mean cumulative function estimates for time to cardiovascular death or total HHF in the overall population. C, Kaplan-Meier estimates for time to HF-related death or first HHF in the overall population. D, Mean cumulative function estimates for time to HF-related death or total HHF in the overall population. E, Kaplan-Meier estimates for time to first HHF in the overall population. F, Mean cumulative function estimates for time to total HHF in the overall population. HF indicates heart failure; and HHF, hospitalization for heart failure.

Figure 3.

Time to cardiovascular death or first hospitalization for heart failure in key prespecified and post hoc subgroups. BMI indicates body mass index; CVD, cardiovascular disease; GLP-1RA, glucagon-like peptide 1 receptor agonist; PY, patient-years; and SGLT-2i, sodium-glucose cotransporter-2 inhibitor.

Figure 4.

HF-associated outcomes including first HHF, overall, and by history of HF. CV indicates cardiovascular; HF, heart failure; HHF, hospitalization for heart failure; and PY, patient-years.

Figure 5.

HF-associated outcomes including total HHF, overall, and by history of HF. CV indicates cardiovascular; HF, heart failure; HHF, hospitalization for heart failure; and PY, patient-years. *Event rate (n/100 PY) is the sum of all events in all patients divided by overall time under risk for all patients.