Finerenone reduces composite cardiovascular outcome and risk of decreased eGFR, but increases risk of hyperkalemia

Reference

Bakris GL, Agarwal R, Anker SD, et al, for the FIDELIO-DKD Investigators. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med 2020;383(23):2219-2229.

Synopsis

Finerenone is a selective mineralocorticoid receptor antagonist that has been shown to reduce the disease-oriented outcome of albuminuria in patients with CKD. This study identified 5734 patients with T2DM and CKD, defined as either moderate albuminuria plus eGFR between 25 and 59 mL per minute per 1.73m^2 plus diabetic retinopathy, or severe albuminuria plus eGFR 25 to 74 mL per minute per 1.73m^2. There was a run-in period during which angiotensin-converting enzyme inhibitor or angiotensin receptor blocker doses were maximized, followed by randomization to receive finerenone 10 mg once daily (titrated to 20 mg in approximately 50%) or placebo. Groups were balanced at the beginning of the study, analysis was by intention to treat, and patients were followed up for a median of 2.6 years. The primary outcome was a composite of kidney failure, a decrease of eGFR by 40% for at least one month, or death due to renal causes and was less likely in the intervention group (17.8% vs 21.1%; P = .001; number needed to treat [NNT] = 33 over 2.6 years), largely due to fewer patients having a significant decrease in eGFR. There were only 2 deaths due to renal causes in each group, and the difference in kidney failure was not statistically significant (7.3% vs 8.3%). The secondary composite outcome of cardiovascular mortality, nonfatal myocardial infarction or stroke, or hospitalization for heart failure was less common (13.0% vs 14.8%; P = .03; NNT = 56 over 2.6 years). Hyperkalemia resulting in death or hospitalization, or hyperkalemia that was considered life-threatening, was more common in the intervention group (1.6% vs 0.4%; number needed to treat to harm = 83 over 2.6 years). This study, including the data analysis, was industry sponsored.