ESC: Finerenone Improves Outcomes in Patients with Mild-to-Moderate Kidney Disease and Diabetes

FIGARO-DKD trial presented in a Hot Line Session at ESC Congress 2021

Sophia Antipolis, France – 28 Aug 2021 – Finerenone reduces the risk of cardiovascular morbidity and mortality in patients with mild-to-moderate kidney disease and type 2 diabetes. That’s the finding of late breaking research presented in a Hot Line session today at ESC Congress 2021¹ and published in the New England Journal of Medicine².

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 optimized 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 randomization) 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 randomized 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 hospitalization 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 hospitalization 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 Michigan, Ann Arbor, US said: “Finerenone improved cardiovascular outcomes in patients with mild-to-moderate kidney disease and type 2 diabetes treated with optimized 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.”

This press release accompanies both a presentation and an ESC press conference at ESC Congress 2021. It does not necessarily reflect the opinion of the European Society of Cardiology.

Funding: FIGARO-DKD was funded by Bayer AG.

Disclosures: Bertram Pitt reports consultant fees for AstraZeneca, Bayer, Boehringer Ingelheim/Lilly, Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, KBP Biosciences, Phasebio, Proton Intel, Sanofi/Lexicon, Sarfez, scPharmaceuticals, SQ Innovation, Tricida and Vifor/Relypsa; he has stock options for  Brainstorm Medical, Cereno Scientific G3 Pharmaceuticals, KBP Biosciences, Proton Intel, Sarfez, scPharmaceuticals, SQ Innovation, Tricida and Vifor/Relypsa; he also holds a patent for site-specific delivery of eplerenone to the myocardium (US patent #9931412) and a provisional patent for histone-acetylation-modulating agents for the treatment and prevention of organ injury (provisional patent US 63/045,784).

About the European Society of Cardiology

The ESC brings together health care professionals from more than 150 countries, working to advance cardiovascular medicine and help people to live longer, healthier lives.

About ESC Congress 2021 - The Digital Experience

It is the world’s largest gathering of cardiovascular professionals, disseminating ground-breaking science in a new digital format. Online each day – from 27 to 30 August. Explore the scientific programme. More information is available from the ESC Press Office at press@escardio.org.

References

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.