Beneficial effects of non-steroidal MRA on HF-related outcomes in CKD and T2DM

Introduction and methods

Background

In patients with T2DM, the risk of CV death and HF increases with decreasing kidney function (eGFR) and increasing albuminuria (urine albumin-to-creatinine ratio, UACR) [1,2]. Finerenone is a selective, non-steroidal MRA approved by the FDA and EMA for the treatment of CKD in adult patients with T2DM [3,4]. Previously, a pooled analysis of individual patient data from the FIDELIO-DKD and FIGARO-DKD trials (FIDELITY study) showed that treatment with finerenone improves cardiorenal outcomes in these patients [5-7]. However, it is unclear whether this also applies to HF-related outcomes.

Aim of the study

The aim of this analysis of the FIDELITY study was to examine the effects of finerenone on HF-related outcomes in adult patients with CKD and T2DM, stratified by baseline eGFR and/or UACR.

Methods

The researchers performed a pooled analysis of individual patient data from the FIDELIO-DKD and FIGARO-DKD trials (FIDELITY study). In these placebo-controlled, double-blind, randomized phase 3 studies, a total of 13,026 adults with CKD (defined as UACR 30-<300 mg/g with eGFR ≥25 to<60 mL/min per 1.73 m2 and retinopathy in FIDELIO-DKD or eGFR 25 to ≤90 mL/min per 1.73 m2 in FIGARO-DKD; or UACR of 300-5000 mg/g and eGFR ≥25 to <75 mL/min/1.73 m2 in FIDELIO-DKD or ≥60 mL/min/1.73 m2 in FIGARO-DKD) and T2DM were randomized to treatment with once-daily 10 or 20 mg finerenone or placebo. Additional inclusion criteria were treatment with an ACEi or ARB for ≥4 weeks at a maximum tolerated labeled dose and a serum potassium concentration 4.8 mmol/L. Patients with HFrEF and NYHA class II-IV symptoms, patients with a history of stroke, TIA or ACS, and patients hospitalized for worsening HF within the past 30 days were excluded from participation.

Outcomes

'Time-to-event' outcomes were: (a) first hospitalization for HF; (b) CV death or first hospitalization for HF; (c) recurrent hospitalization for HF; and (d) CV death or recurrent hospitalization for HF. These outcomes were analyzed in the overall study population and in subgroups based on baseline eGFR (<60 and ≥60 mL/min per 1.73 m2) and/or UACR (<300 and ≥300 mg/g).

Main results

Overall study population

• Compared with placebo, finerenone reduced the risk of first hospitalization for HF (HR: 0.78; 95%CI: 0.66-0.92; P=0.003), CV death or first hospitalization for HF (HR: 0.83; 95%CI: 0.74-0.93; P=0.002), recurrent hospitalization for HF (HR: 0.79; 95%CI: 0.64-0.96; P=0.021), and CV death or recurrent hospitalization for HF (HR: 0.82; 95%CI: 0.72-0.95; P=0.006).

Subgroups

• There was no difference in the reductions of HF-related outcomes with finerenone vs. placebo in patients with a baseline eGFR ≥60 mL/min per 1.73 m2 compared with patients with baseline <60 mL/min per 1.73 m2 (Pinteractions≥0.15).
• Consistently, reductions in risk of HF-related outcomes with finerenone vs. placebo in patients with UACR <300 mg/g compared with patients with UACR ≥300 mg/g were not significantly different (Pinteractions>0.20).
• The largest relative risk reduction was seen in the combined subgroup of patients with an eGFR ≥60 mL/min per 1.73 m2 and a UACR <300 mg/g (43-70% reduction across all HF-related outcomes).

Conclusion

References

Find this article online at JACC Heart Fail.