Kidney outcomes with finerenone: an analysis from the FIGARO-DKD study

Abstract

Background In FIGARO-DKD, finerenone reduced the risk of cardiovascular events in patients with type 2 diabetes (T2D) and stage 1–4 chronic kidney disease (CKD). In FIDELIO-DKD, finerenone improved kidney and cardiovascular outcomes in patients with advanced CKD. This analysis further explores kidney outcomes in FIGARO-DKD. Methods FIGARO-DKD (NCT02545049) included patients with urine albumin-to-creatinine ratio (UACR) 30–<300 mg/g and estimated glomerular filtration rate (eGFR) 25–90 mL/min/1.73 m2 or UACR 300–5000 mg/g and eGFR ≥ 60 mL/min/1.73 m2. Outcomes included two composite kidney endpoints of kidney failure, renal death and with either a sustained decrease from baseline of ≥ 40% or ≥ 57% in eGFR for ≥ 4 weeks. Change in of albuminuria and eGFR slope were also analysed. Kidney and CV outcomes were evaluated by baseline UACR. Results A lower incidence rate for the eGFR ≥ 40% kidney composite endpoint was observed with finerenone compared with placebo, but the between-group difference was not significant (HR = 0.87; 95%CI 0.76–1.01; P = 0.069). A greater treatment effect was observed on the eGFR ≥ 57% kidney composite endpoint (HR = 0.77; 95%CI 0.60–0.99; P = 0.041) with a 36% relative risk reduction for end-stage kidney disease. A larger magnitude of effect on kidney outcomes was observed with finerenone versus placebo for patients with severely increased albuminuria than with moderately increased albuminuria. Improvements in UACR, eGFR slope and cardiovascular risk were evident in both subgroups with finerenone. Conclusions The present analyses suggest that finerenone protects against kidney disease progression and cardiovascular events in patients with T2D and early- or late-stage CKD.

The non-steroidal mineralocorticoid receptor antagonist finerenone is a novel therapeutic option for patients with Type 2 diabetes and chronic kidney disease

“…(51) The incidence of the first secondary outcome in FIGARO-DKD (a composite of kidney failure, a sustained decrease of at least 40% from baseline in the eGFR, or death from renal causes), was not significantly different in finerenone versus placebo (HR: 0.87, 95%CI: 0.76 -1.01, p =0.069). (51,52) When analyzing the composite outcome that included a sustained decrease in eGFR of at least 57% from baseline, a significant risk reduction was observed (HR= 0.77, 95%CI: 0.60 -0.99, p= 0.041). (51,52) Further exploratory analyses showed that a larger effect of finerenone vs. placebo on kidney outcomes is observed in patients with more severe albuminuria (uACR: 300-5000 mg/g) as compared to patients with uACR 30-299 mg/g.…”

“…(51,52) When analyzing the composite outcome that included a sustained decrease in eGFR of at least 57% from baseline, a significant risk reduction was observed (HR= 0.77, 95%CI: 0.60 -0.99, p= 0.041). (51,52) Further exploratory analyses showed that a larger effect of finerenone vs. placebo on kidney outcomes is observed in patients with more severe albuminuria (uACR: 300-5000 mg/g) as compared to patients with uACR 30-299 mg/g. ( 52) This larger effect observed in patients with high albuminuria levels might explain the lack of significant effect on the first secondary outcome in FIGARO-DKD in which patients with less albuminuria were included as compared to the FIDELITY analysis in which a bigger spectrum of patients with low and high albuminuria were included (see below).…”

“…Of note, the effect of finerenone on uACR reduction, slowing eGFR decline and cardiovascular risk reduction was similar in both albuminuria subgroups. (52) Importantly, a prespecified analysis from the FIGARO-DKD trial found that finerenone reduced the risk of new-onset heart failure by 32% (HR: 0.68, 95%CI: 0.50 -0.93, p=0.016), with significant reductions in the risk of cardiovascular death or hospitalization for a first heart failure (18%, p=0.011) and the risk of total hospitalizations for heart failure (30%, p=0.018). Pre-existing heart failure did not modify the effect of finerenone on these outcomes.…”

Nonsteroidal Mineralocorticoid Receptor Antagonism by Finerenone—Translational Aspects and Clinical Perspectives across Multiple Organ Systems

“…Accordingly, in the FIDELIO-DKD study, finerenone treatment resulted in a modest reduction in office blood pressure (mean change in systolic blood pressure from baseline to month 12: −2.1 mmHg with finerenone vs. 0.9 mmHg with placebo) [ 20 ] that was responsible for a small proportion of the clinical effect of finerenone in both the kidneys and the heart [ 127 ]. By 4 months of treatment, a significant reduction in albuminuria (UACR) was observed with finerenone vs. placebo (31–32% lower with finerenone) [ 20 , 22 , 128 ]. Notably, this was the first measurement of UACR taken in the FIDELIO-DKD and FIGARO-DKD studies after the initiation of treatment.…”

“…In addition to these early effects, results from FIDELIO-DKD and FIGARO-DKD also illustrated a longer-term action of finerenone, hypothesized to be due to a reduction in MR-mediated inflammation and fibrosis [ 19 ]. These benefits have been observed as a reduced rate of long-term eGFR decline vs. placebo, with the intersection of the least-squares mean change from baseline in the eGFR slopes at 28 months in FIDELIO-DKD and 36 months in FIGARO-DKD [ 20 , 128 ]. Effects of finerenone on clinical renal outcomes are also slower to develop, as seen in the later divergence around 20–24 months of the Kaplan–Meier curves for the composite kidney outcomes of time to end-stage kidney disease, sustained ≥40% or 57% decreases in eGFR from baseline, or renal death [ 20 , 21 , 22 ].…”