Incidence of death from cardiovascular causes was lower in the finerenone group (458 of 3686 patients) compared to the placebo group (519 of 3666 patients).
Data from the FIDELIO-DKD trial showed finerenone improved kidney outcomes in patients with stage 3 or 4 chronic kidney disease (CKD) with severely elevated albuminuria and type 2 diabetes with a high kidney risk.
As a result, the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial evaluated if treatment would lead to lower risk of cardiovascular events and death from CV causes among patients with stage 2 - 4 CKD and moderately elevated albuminuria or stage 1 or 2 CKD and severely increased albuminuria.
The study was presented online at the European Society of Cardiology (ESC) 2021 Congress.
Investigators, led by Bertram Pitt, MD, at the Department of Medicine, University of Michigan School of Medicine, found finerenone therapy improved CV outcomes compared with placebo in patients with T2D and stage 2 to 4 CKD with moderately elevated albuminuria or stage 1 or 2 CKD with severely elevated albuminuria.
The team performed a phase 3, double-blind trial in order to randomly assign patients with CKD and T2D to receive finerenone or placebo. Eligible patients were adults ≥18 years of age with CKD or T2D treated with a renin angiotensin system (RAS) inhibitor at the maximum dose.
In addition, patients had a urinary albumin-to-creatinine ratio of 30 to <300 and an estimated glomerular filtration rate (eGFR) of 25 - 90 mL/minute per 1.73 m2(stage 2 to 4 CKD) or a urinary albumin-to-creatinine ratio of 300 - 5000 and an eGFR of ≥60 ml per minute 1.73 m2 (stage 1 or 2 CKD).
Investigators assessed the primary outcome as a composite of death from CV causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure, with the secondary outcome consisting of a composite of kidney failure, sustained decrease from baseline of ≥40% in the eGFR, or death from renal causes.
At the run-in period, RAS inhibitor therapy was adjusted to maximum label dose that did not cause unacceptable side effects. Patients were randomized 1:1 to oral finerenone or placebo and trial visits were conducted every 4 months until trial completion.
The study included an assessment of safety as investigator-reported adverse events and central laboratory testing.
Between September 2015 - October 2018, investigators screened a total of 19,381 patients from 48 countries, with 7437 patients undergoing randomization.
A median follow-up of 3.4 years took place with patients included in the analysis, with 7334 of 7352 patients (99.8%) included in the primary analysis.
Data show the mean daily dose of finerenone was 17.5 mg and mean daily dose of placebo was 18.2 mg, with mean adherence to the trial regimen at 91.5% in the finerenone group and 92.9% in the placebo group.
Investigators noted the incidence of death from CV causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure was significantly lower in the finerenone group compared to the placebo group (458 of 3686 patients, 12.4% versus 519 of 3666 patients 14.2% hazard ratio, 0.87; 95% CI, 0.76 to 0.98; P = .03).
Further, they specifically noted the benefit was a result of lower incidence of hospitalization for heart failure in the finerenone group (117 patients, 3.2%) compared to the placebo group (163 patients, 4.4%), HR, 0.71; 95% CI, 0.56 - 0.90).
In the secondary composite outcome, data show no significant between-group difference in the incidence of kidney failure, sustained decrease from baseline of ≥40% in the eGFR, or death from renal causes.
In the finerenone group, the secondary composite occurred in 350 patients (9.5%) in the finerenone group and in 395 patients (10.8%) in the placebo group (HR, 0.87; 95% CI, 0.76 - 1.01).
Reports of adverse events were similar in the 2 groups, in 31.4% of patients treated with finerenone had a serious adverse event, compared with 33.2% of those who received placebo. Incidence of hyperkalemia-related discontinuation of the trial regimen was higher with the finerenone (1.2%) compared with placebo (0.4%).
Overall, in the FIGARO-DKD, investigators determined patients with T2D and CKD assigned to the finerenone group had lower risk of primary composite of death, in comparison to placebo, due to a lower incidence of hospitalization for heart failure.
In an interview with HCPLive regarding the findings, Pitt said FIGARO-DKD helped deliver indication that finerenone is known to be “effective and really well-tolerated” for patients with comorbid CKD—comforts not well-established with a single drug in the patient population.
“Yes, you’re going to have to watch it, you’ll have to monitor it, but it is well-tolerated and really effective,” he said.
“In both trials, the observed cardiovascular benefits of finerenone therapy were clinically meaningful and were obtained on a background of guideline-directed therapy, including RAS blockade at a maximum labeled dose that did not cause unacceptable side effects, as well as frequent use of cardiovascular medications (e.g., statins) and well-controlled glycated hemoglobin and blood- pressure levels,” investigators wrote.
The study, “Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes,” was published online in the New England Journal of Medicine.