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

Presented at the ESC HF congress 2021 by: Gerasimos Filippatos (Athens, Greece)

Introduction and Methods

CKD, T2DM and HF commonly coexist, and patients with all these three conditions have unfavorable outcomes. Guidelines recommend that patients with HFrEF are treated with a steroidal MRA, such as spironolactone or eplerenone to reduce CV events and improve survival. To date, RCTs have failed to demonstrated a clear benefit of steroidal MRAs in patients with HFrEF.

Finerenone is a selective, nonsteroidal MRA which has potent anti-inflammatory and anti-fibrotic effects in the kidney and CV system shown in animal models. In de FIDELIO-DKD trial, treatment of finerenone reduced CKD progression by 18% and CV morbidity and mortality by 14% compared to placebo, in patients with advanced CKD and T2M. 5734 Patients were enrolled and the trial had a median follow-up of 2.6 years.

In this subgroup analysis, the effect of finerenone on kidney and CV outcomes was explored in patients with CKD and T2DM with and without a history of HF. Also, the effect of finerenone compared to placebo on the composite outcome of CV death or first hospitalization for HF and the composite of CV death and recurrent hospitalization for HF were examined.

In the FIDELIO-DKD trial, HFrEF patients with NYHA Class II-IV (class IA recommendation for treatment with an MRA) and patients with a recent hospitalization for worsening HF were excluded. In this subanalysis, there were 436 (7.7%) patients with a history of HF at baseline, who likely had a diagnosis of HFpEF or HFmrEF.

Main results

• Finerenone reduced the risk of the composite CV outcome (time to CV death, non-fatal MI, non-fatal stroke, hospitalization for HF) compared to placebo, irrespective of history of HF (in patients with history of HF: HR 0.73, 95%CIL 0.50-1.08 and in patients without a history of HF: HR 0.90, 95%CI: 0.77-1.04, Pinteraction=0.33). Same findings were observed for components of the composite CV outcome.
• The composite renal endpoint (kidney failure, sustained decrease of eGFR ≥40%, renal death) was reduced by finerenone compared to placebo, irrespective of history of HF (in patients with a history of HF: HR 0.79; 95%CI: 0.52-1.20, and in patients without a history of HF: HR 0.83, 95%CI: 0.73-0.94, Pinteraction=0.83).
• Incidence of the composite outcome of CV death or HHF in the overall population was lower in the finerenone group compared to the placebo group, but the difference did not reach statistical significance (HR 0.83, 95%CI: 0.66-1.04, P=0.098 for the first event and HR 0.87, 95CI%: 0.70-1.07, P=0.18 for total events).
• Incidence of first and total HHF events in the overall study population was lower in the finerenone group compared to the placebo group, but the difference was not statistically significant.
• Incidence of overall TEAEs was similar between treatment arms irrespective of HF history.

Conclusion

The nonsteroidal MRA finerenone reduced CV and kidney outcomes compared to placebo in patients with CKD and T2DM, irrespective of pre-existing HF status.

Additional data from FIGARO-DKD and the ongoing FINEARTS-HF trials will provide an opportunity to further examine the effect of finerenone in patients with HF, said Gerasimos Filippatos.

– Our coverage of ESC HF 2021 is based on the information provided during the congress –