CV and renal outcomes reduced by nonsteroidal MRA in T2DM across spectrum of kidney disease
FIDELITY Analysis: finerenone in mild-to-severe chronic kidney disease and type 2 diabetes
Presented at the ESC congress 2021 by: Prof. Gerasimos Filippatos, MD - Athens, Greece
Introduction and methods
FIDELITY was a prespecified individual patient data pooled analysis of FIDELIO-DKD and FIGARO-DKD. Both trials investigated the effects of the nonsteroidal MRA finerenone on CV and renal outcomes in patients with diabetes and CKD treated with optimized RAS blockade and with a serum potassium of ≤4.8 mmol/L. Patients with symptomatic HFrEF were excluded. FIDELIO-DKD enrolled patients with predominantly advanced kidney disease, while FIGARO-DKD enrolled patients with mild-to-moderate kidney disease. Participants were randomized in a 1:1 ratio to receive either oral finerenone (10 or 20 mg) or placebo, once daily.
The FIDELITY analysis investigated the efficacy and safety of finerenone in patients with diabetes across the spectrum of kidney disease. A total of 13,026 patients were included in this analysis. The primary endpoint of the FIDELITY analysis was time to first occurrence of a composite of CV death, nonfatal MI, nonfatal stroke or HF hospitalization. The secondary endpoint was time to first occurrence of a composite of kidney failure, decrease in eGFR by ≥57% from baseline sustained for at least 4 weeks, or renal death. Median follow-up was 3.0 years.
- Finerenone reduced the risk of the primary composite outcome of time to CV death, nonfatal MI, nonfatal stroke or HF hospitalization by 14%, compared with placebo (HR 0.86, 95%CI 0.78-0.95, P=0.0018). The number needed to treat after 3 years was 46 (95%CI 29-109).
- The risk of the composite renal outcome of time to kidney failure, sustained decrease in eGFR by ≥57% from baseline, or renal death was 23% lower with finerenone compared to placebo (HR 0.77, 95%CI 0.67-0.88, P=0.0002). The number needed to treat after 3 years was 60 (95%CI 38-142).
- The risk of end-stage kidney disease, defined as the initiation of chronic dialysis or kidney transplantation, was significantly reduced by 20% with finerenone, compared to placebo.
- Hyperkalemia was more common in patients in the finerenone group, compared to patients in the placebo group (14.0% vs. 6.9%). However, permanent discontinuation of study drug due to hyperkalemia was infrequent in both treatment groups (1.7% vs. 0.6%, respectively).
This analysis showed that the nonsteroidal MRA finerenone reduced the risk of CV morbidity and mortality by 14% and reduced the risk of CKD progression by 23% in patients with T2DM and mild-to-severe CKD.
Prof. Filippatos also said: ‘UACR monitoring in patients with T2DM is important for the identification of patients who can benefit from treatment with finerenone, independent of eGFR.’
-Our reporting is based on the information provided at the ESC Congress-