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 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 to editors
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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).
References and 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.
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New England Journal of Medicine
Pitt B et al. Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes (FIGARO-DKD)
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