Beneficial effects of nonsteroidal MRA on mortality in patients with CKD and T2DM
Finerenone and effects on mortality in chronic kidney disease and type 2 diabetes: a FIDELITY analysis
Introduction and methods
Patients with CKD and T2DM have an increased all-cause mortality and CV mortality risk . Finerenone, a selective nonsteroidal MRA, has cardiorenal benefits for patients with CKD and T2DM, as demonstrated by the complementary FIDELIO-DKD and FIGARO-DKD trials and their pooled FIDELITY (FInerenone in chronic kiDney diseasE and type 2 diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial programme analYsis) analysis [2-4].
Aim of the study
The authors investigated the causes of mortality in the FIDELITY dataset, and investigated whether finerenone protects patients with CKD and T2DM from mortality.
This is a prespecified analysis of the FIDELIO-DKD and FIGARO-DKD trials, which were international, randomized, double-blind, placebo-controlled, multicenter trials. Key exclusion criteria were patients with HFrEF and non-diabetic kidney disease. In this analysis, a total of 13,026 patients with CKD and T2DM were included who were randomized to receive finerenone at a dose of 20 mg (10 mg if eGFR <60 mL/min/1.73 m2; 6519 patients) or placebo (6507 patients). Most patients (99.8%) were on RAS inhibitors as maximal tolerated dose of an ACEi or ARB for ≥4 weeks before screening was required.
Outcomes were all-cause mortality, CV mortality, renal mortality, and non-CV, non-renal mortality.
- In the finerenone group 552 patients (8.5%) died compared to 614 patients (9.4%) in the placebo group (HR: 0.89; 95%CI: 0.79–1.00; P=0.051).
- In the finerenone group there were 332 (4.9%) CV-related deaths compared to 364 (5.6%) in the placebo group (HR: 0.88; 95%CI: 0.76–1.02; P=0.092).
- The incidence of all-cause mortality and CV mortality were significantly lower with finerenone compared to placebo. 280 finerenone-treated patients (4.3%) vs. 344 placebo-treated patients (5.3%) died of all-causes (HR: 0.82, 95%CI: 0.70–0.96, P=0.014). CV mortality occurred in 189 finerenone-treated patients (2.9%) vs. 233 placebo-treated patients (3.6%; HR: 0.82, 95%CI: 0.67–0.99, P=0.040).
Causes of mortality
- In the total study population, the most common cause of mortality was CV-related in both the finerenone and placebo groups (respectively, 4.9% vs. 5.6%). Most of these deaths were undetermined CV mortality and sudden cardiac death (respectively, 2.2% vs. 2.4% and 1.3% vs. 1.8%).
- Finerenone reduced the incidence of sudden cardiac death compared to placebo (88 patients (1.3%) vs. 115 patients (1.8%; HR: 0.75; 95%CI: 0.57–0.996; P=0.046).
- The incidence of non-CV, non-renal mortality occurred in 228 finerenone-treated patients (3.5%) and 246 placebo-treated patients (3.8%). This includes mortality from malignancy, infection, and other causes. The incidence of renal mortality was lower than 0.1% in both treatment groups.
- Finerenone reduced the incidence of all-cause mortality, CV mortality, and non-CV, non-renal mortality compared to placebo in most KDIGO risk groups. Exemptions were that finerenone did not reduce the incidence for all-cause mortality and CV mortality in very high risk patients, and CV mortality in low risk patients.
- Event probability analysis revealed that the effect of finerenone on all-cause mortality, CV mortality and sudden cardiac death at 4 years was consistent regardless of baseline eGFR, baseline UACR or serum potassium levels at 4 months. However, the effect of finerenone was more pronounced in patients with higher levels of baseline eGFR or with lower serum potassium levels at 4 months.
Using the FIDELITY dataset, the authors demonstrated that finerenone reduced all-cause mortality and CV mortality in patients with CKD and T2DM. Moreover, finerenone lowered the incidence of sudden cardiac death compared to placebo. The benefits of finerenone on survival was greater in patients with higher baseline eGFR, indicating that early treatment is warranted to maximize the protective effects of finerenone in this patient population.