Finerenone reduces the risk for cardiovascular and renal outcomes in patients with type 2 diabetes who have mild chronic kidney disease (CKD) and those with diagnosed diabetic kidney disease, investigators announced at ESC Congress 2021. The nonsteroidal mineralocorticoid receptor antagonist (MRA) carries an increased risk for hyperkalemia.
FIDELITY was a prespecified meta-analysis combining individual patient data from 13,026 patients in the FIDELIO-DKD (ClinicalTrials.gov: NCT02540993) and FIGARO-DKD (ClinicalTrials.gov: NCT02545049) randomized trials. CKD severity was defined according to categories of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR).
The primary endpoint was time to first occurrence of a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. The secondary endpoint was time to first occurrence of a composite of kidney failure, decrease in eGFR by 57% or more, or renal death.
Over a median of 3.0 years of follow-up, the composite cardiovascular endpoint occurred in a lower proportion of patients receiving finerenone compared with placebo: 12.7% vs 14.4%. Finerenone reduced the risk for the cardiovascular outcome by a significant 14%.
The composite renal endpoint also occurred in a lower proportion of patients receiving finerenone vs placebo: 5.5% vs 7.1%. Finerenone reduced the risk for the renal outcome by a significant 23%. No comparison between groups could be made for the renal death component, however, because it was a rare event.
At baseline, all patients received optimized renin-angiotensin system blockade and had a serum potassium level of 4.8 mmol/L or less. Patients with chronic heart failure with reduced ejection fraction were excluded from the trials.
Hyperkalemia was more common with finerenone than placebo: 14.0% vs 6.9%. Discontinuation of treatment due to hyperkalemia occurred in 1.7% of the finerenone and 0.6% of the placebo group. Other safety outcomes appeared similar between groups.
“The FIDELITY analysis demonstrates that finerenone reduced the risk of cardiovascular and kidney outcomes compared with placebo across the spectrum of chronic kidney disease in patients with type 2 diabetes,” study author Gerasimos Filippatos, MD, of the National and Kapodistrian University of Athens Medical School in Greece stated in an ESC Congress press release. “The cardiovascular benefits of the drug were consistent across eGFR and UACR categories, indicating that treatment should be initiated in the early stages of renal disease.”
Finerenone is a newly FDA approved nonsteroidal MRA indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure in adult patients with CKD associated with type 2 diabetes. The recommended starting dosage is 10 mg or 20 mg orally once daily based on eGFR and serum potassium thresholds. The FDA label includes a hyperkalemia warning. Serum potassium levels should be measured before treatment initiation and not started if levels exceed 5.0 mEq/L. Serum potassium levels should be monitored during treatment with finerenone dose adjustments as needed.
Disclosure: This research was supported by Bayer AG. Please see the original reference for a full list of disclosures.
Finerenone benefits patients with diabetes across spectrum of kidney disease [press release]. ESC Congress; August 28, 2021.
Kerendia [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2021.