Finerenone improves outcomes in patients with mild-to-moderate kidney disease and diabetes

Diabetic kidney disease develops in approximately 40% of patients with diabetes and is the leading cause of chronic kidney disease worldwide.³ Some patients progress to end-stage renal disease, but most die from cardiovascular diseases and infections before needing kidney replacement therapy.³

The FIDELIO-DKD trial previously reported that finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), slowed progression of kidney disease and improved cardiovascular outcomes in patients with predominantly advanced kidney disease and type 2 diabetes.⁴ FIGARO-DKD investigated cardiovascular and renal outcomes with finerenone treatment in patients with mild-to-moderate kidney disease and type 2 diabetes.

Regarding the study population, FIGARO-DKD enrolled adults with type 2 diabetes and mild-to-moderate kidney disease⁵ treated with optimised renin-angiotensin system (RAS) blockade. As finerenone increases serum potassium levels by an average of approximately 0.2 mmol/L, patients had to have serum potassium 4.8 mmol/L or below at the run-in and screening visits (but not at randomisation) so that levels could be maintained at an optimal range for most patients, i.e. around 5.0 mmol/L or below. Nevertheless, study drug could be continued up to a potassium level of 5.5 mmol/L. Patients with symptomatic chronic heart failure with reduced ejection fraction were excluded since steroidal MRA treatment is a class 1A recommendation and withholding therapy for the duration of the trial would have been unethical.

A total of 7,437 patients in 48 countries were randomised 1:1 to oral finerenone (10 or 20 mg) or placebo once-daily. The average age was 64.1 years and 69.4% were men. The primary endpoint was a cardiovascular composite of time to cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or hospitalisation for heart failure.

During a median follow-up of 3.4 years, the primary endpoint occurred in 458 (12.4%) and 519 (14.2%) patients in the finerenone and placebo groups, respectively. The relative risk of this endpoint was significantly reduced by 13% with finerenone versus placebo (hazard ratio [HR] 0.87; 95% confidence interval [CI] 0.76-0.98; p=0.03). The observed cardiovascular benefit was largely driven by a 29% reduction in hospitalisation for heart failure.

The key secondary outcome was a composite of kidney failure, sustained decrease in estimated glomerular filtration rate (eGFR) by 40% or more from baseline, or renal death.

This endpoint occurred in 350 (9.5%) and 395 (10.8%) patients in the finerenone and placebo groups, respectively (HR 0.87; 95% CI 0.76-1.01; p=0.07).

Regarding other secondary outcomes, the composite of kidney failure, sustained decrease in eGFR by 57% or more from baseline, or renal death occurred in 108 (2.9%) and 139 (3.8%) patients in the finerenone and placebo groups, respectively (HR 0.77; 95% CI 0.60-0.99). End-stage kidney disease occurred in 32 (0.9%) and 49 (1.3%) patients in the finerenone and placebo groups, respectively (HR 0.64; 95% CI 0.41-<1.00).

Regarding safety, the overall frequency of adverse events did not differ between groups. Hyperkalaemia was increased with finerenone (10.8%) compared to placebo (5.3%), but subsequent discontinuation of study drug was low (1.2% with finerenone versus 0.4% with placebo).

Study author Professor Bertram Pitt of the University of Michingan, Ann Arbor, US saif : Finerone improved cardiovascular outcomes in patients with mild-to-moderate kidney disease and type 2 diabetes treated with optimised RAS blockade and with well-controlled blood pressure and diabetes. The benefits of finerenone were consistent across eGFR and urine albumin-to-creatinine ratio (UACR) categories. Together with FIDELIO-DKD, the results support the use of finerenone to improve cardiorenal outcomes across the spectrum of kidney disease and type 2 diabetes."

Notes

¹FIGARO-DKD: finerenone in patients with chronic kidney disease and type 2 diabetes.

² Pitt B et al. Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes (FIGARO-DKD) N Engl J Med. 10.1056/NEJMoa2110956

³Alicic RZ, Rooney MT, Tuttle KR, et al. Diabetic kidney disease: challenges, progress, and possibilities. Clin J Am Soc Nephrol. 2017;12:2032-2045.

⁴Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383:2219-2229.

⁵Mild-to-moderate kidney disease was defined as: urine albumin-to-creatinine ratio (UACR) ≥30-<300 mg/g and estimated glomerular filtration rate (eGFR) ≥25-≤90 mL/min/1.73m² or UACR ≥300-≤5000 mg/g and eGFR ≥60 mL/min/1.73m².