Reviwer: Dr. Alper Karakuş

Trial: Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease - FIGARO-DKD

Presented Congress: ESC 2021

Full Text Link: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2110956

Background:

In the FIDELIO-DKD study, finerenone was shown to reduce cardiovascular (CV) adverse events and mortality in type 2 diabetes (T2DM) patients with severe chronic kidney disease (CKD).

Objective:

FIGARO-DKD aimed to evaluate the safety and efficacy of finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, in reducing CV events in patients with type 2 DM and CKD.

Method:

The study population consisted of patients with a glomerular filtration rate (GFR) of 25-90 ml/min/m2 and a urinary albumin-creatinine ratio of 300-5000 (stage 2-4 CKD) and receiving the highest dose of angiotensin system blocker. Patients with symptomatic heart failure with low ejection fraction and patients with potassium levels above 4.8 mEq/L were excluded from the study. Eligible patients were randomized 1:1 to the finerenon (n = 3.686) or placebo (n = 3.666) groups. The primary outcome was considered a composite of cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, or hospitalization for heart failure and was evaluated in a time-to-event analysis.

Results:

Considering the demographic characteristics of the study population, where the mean follow-up period was 3.4 years, it was seen that the mean patient age was 64.1 years, and the female sex ratio was 31%. The composite primary efficacy outcome ratio was 12.4% in the finerenone arm and 14.2% in the placebo arm (HR:0.87; 95% CI, 0.76 to 0.98, p=0.03). This difference was primarily attributed to the 29% relative reduction in heart failure hospitalizations (HR:0.71; 95% CI, 0.56 to 0.90). The secondary composite outcome, defined as CKD progression, renal failure, and kidney-related death, occurred in 350 patients (9.5%) in the finerenone group and 395 (10.8%) in the placebo group (HR, 0.87; 95% CI, 0). .76 to 1.01). However, the overall frequency of adverse events did not differ statistically between groups. Discontinuation of the treatment regimen due to hyperkalemia was 1.2% in the finerenone arm and 0.4% in the placebo arm. In the pooled analysis that included 13,171 patients from the FIDELIO-DKD and FIGARO-DKD studies, CV death, MI, stroke, hospitalization for heart failure were seen in 12.7% in the finerenone arm versus 14.4% in the placebo arm (HR 0.86, 95% CI 0.78 to 0.95). , p = 0.0018). Time to renal failure, greater than 57% reduction in eGFR from baseline, or renal loss was 5.5% in the finerenone arm versus 7.1% in the placebo arm (HR 0.77, 95% CI 0.67 to 0.88, p = 0.0002).

Conclusion:

Analysis of the study showed that in patients with Type 2 DM and CKD stage 2-4 with moderately high albuminuria or stage 1-2 CKD with severely elevated albuminuria, finerenone treatment improved cardiovascular outcomes compared to placebo.

Interpretation:

The results of the study show that finerenone has beneficial effects on CV outcomes, mainly hospitalization for heart failure, in patients with T2DM and CKD under treatment with maximal RAS blockade. However, it should be noted that the risk of hyperkalemia is higher with Finerenon and patients with symptomatic HFrEF were excluded from both studies (FIDELIO-DKD and FIGARO-DKD).