Finerenone therapy was found to improve cardiovascular outcomes for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) versus placebo in a phase 3, multicenter, double-blind trial. The findings were published in The New England Journal of Medicine.
The Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIGARO-DKD) trial was conducted by Bayer, the makers of finerenone, between 2015 and 2018 in 48 countries with 7352 randomized patients. Eligible patients with T2D and CKD (stage 1-2 with urinary albumin-to-creatinine ratio of 300-5000 or stage 3-4 with urinary albumin-to-creatinine ratio of 30-<300) receiving the maximum dose of renin-angiotensin system inhibitors were randomized in a 1:1 ratio to to receive finerenone (n=3686) or placebo (n=3666). Patients with an estimated glomerular filtration rate (eFGR) of 25 to less than 60 ml per minute per 1.73 m2 received an initial dose of 10 mg once daily, and those with an eGFR of at least 60 ml per minute per 1.73 m2 received an initial dose of 20 mg once daily.
At 1 month, patients on the lower dose were adjusted to the higher dose as long as their eGFR was stable and serum potassium was £4.8 mmol/L.
The primary endpoint was the composite event of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization and the secondary endpoint was the composite event of kidney failure, a decrease of ³40% from baseline eGFR for ³4 weeks, or renal-associated death.
Patients were aged mean 64.1±9.8 years, 69.4% were men, 71.8% were White, glycated hemoglobin (HbA1c) was 7.7%±1.4%, eGFR was 67.8±21.7 ml/min/1.73 m2, urinary albumin-to-creatinine ratio was median 308 (interquartile range [IQR], 108-740), and serum potassium was 4.33±0.43 mmol/L.
Among the finerenone recipients, risk for the primary endpoint was decreased compared with placebo (hazard ratio [HR], 0.87; 95% CI, 0.76-0.98; P =.03). Separated by event, finerenone significantly reduced risk for heart failure hospitalization (HR, 0.71; 95% CI, 0.56-0.90) but not for the other events.
Risk for the secondary endpoint was similar among groups (9.5% in the finerenone group vs 10.8% in the placebo group). However, finerenone therapy decreased risk for progressing to end-stage kidney disease (HR, 0.64; 95% CI, 0.41-0.9995) and more effectively reduced urinary albumin-to-creatinine ratio by 32%.
Any adverse event occurred among 85.1% and 85.5% and serious adverse events among 31.4% and 33.2% of the finerenone and placebo cohorts, respectively. Hyperkalemia events occurred more among finerenone recipients than placebo (10.8% vs 5.3%, respectively).
The study had some limitations. The latter part of the trial was disrupted by the COVID-19 pandemic, 10 patients were lost to follow-up, and 85 patients were prospectively excluded because of critical Good Clinical Practice violations. Additionally, noted the researchers, few Black patients underwent randomization.
Based on the overall data, the study authors concluded that finerenone improved cardiovascular outcomes among patients with T2D who also had also chronic kidney disease.
Disclosure: The FIGARO-DKD study was funded by Bayer, and multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Pitt B, Filippatos G, Agarwal R, et al for the FIGARO-DKD Investigators. Cardiovascular events with finerenone in kidney disease and Type 2 diabetes. N Engl J Med. Published online August 28, 2021. doi:10.1056/NEJMoa2110956