Beneficial effects of nonsteroidal MRA on mortality in patients with CKD and T2DM

Introduction and methods

Background

Patients with CKD and T2DM have an increased all-cause mortality and CV mortality risk [1]. 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.

-

Methods

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

Outcomes were all-cause mortality, CV mortality, renal mortality, and non-CV, non-renal mortality.

Main results

Intention-to-treat population

• 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).

On-treatment population

• 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.

Subpopulation

• 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.

Conclusion

References

Find this article online at Eur Heart J Cardiovasc Pharmacother.