Hyperkalemia Risk with Finerenone: Results from the FIDELIO-DKD Trial

Abstract

Background: Finerenone reduced risk of cardiorenal outcomes in patients with CKD and type 2 diabetes in the FIDELIO-DKD trial. We report incidences and risk factors for hyperkalemia with finerenone and placebo in FIDELIO-DKD. Methods: This post hoc safety analysis defined hyperkalemia as ≥mild or ≥moderate based on serum potassium concentrations of >5.5 or >6.0 mmol/L, respectively, assessed at all regular visits. Cumulative incidences of hyperkalemia were based on the Aalen-Johansen estimator using death as competing risk. A multivariate Cox proportional hazards model identified significant independent predictors of hyperkalemia. Restricted cubic splines assessed relationships between short-term post-baseline changes in serum potassium or eGFR and subsequent hyperkalemia risk. During the study, serum potassium levels guided drug dosing. Patients in either group who experienced ≥mild hyperkalemia had the study drug withheld until serum potassium was ≤5.0 mmol/L; then the drug was restarted at the 10 mg daily dose. Placebo-treated patients underwent sham treatment interruption and downtitration. Results: Over 2.6 years' median follow-up, 597/2785 (21.4%) and 256/2775 (9.2%) of patients treated with finerenone and placebo, respectively, experienced treatment-emergent ≥mild hyperkalemia; 126/2802 (4.5%) and 38/2796 (1.4%) patients, respectively, experienced moderate hyperkalemia. Independent risk factors for ≥mild hyperkalemia were higher serum potassium, lower eGFR, increased urine albumin-to-creatinine ratio, younger age, female sex, beta-blocker use, and finerenone assignment. Diuretic or sodium-glucose co-transporter-2 inhibitor use reduced risk. In both groups, short-term increases in serum potassium and decreases in eGFR were associated with subsequent hyperkalemia. At month 4, the magnitude of increased hyperkalemia risk for any change from baseline was smaller with finerenone than with placebo Conclusions: Finerenone was independently associated with hyperkalemia. However, routine potassium monitoring and hyperkalemia management strategies employed in FIDELIO-DKD minimized the impact of hyperkalemia, providing a basis for clinical use of finerenone.

Efficacy and Safety of Finerenone in Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

“…The serum potassium concentrations and incidence of hyperkalemia in the finerenone treatment group were increased relative to those in the placebo group. However, patients with high serum potassium baseline levels (especially >4.8 mmol) and poor renal function had a high risk for hyperkalemia whether in the finerenone groups or placebo groups (Agarwal et al, 2021b;Goulooze et al, 2021). Although finerenone was associated with a higher overall risk of hyperkalemia than placebo, a markedly lower incidence of hyperkalemia and lower mean change of potassium concentrations were observed in the finerenone than in the spironolactone group (Pitt et al, 2013;Kintscher et al, 2021).…”

Hyperkalemia in Diabetes Mellitus Setting

“…However, when serum K + levels were analyzed in the FIDELIO-DKD study, over 2.6 years’ median follow-up, 21.4% of patients treated with finerenone experienced treatment-emergent ≥ mild hyperkalemia (defined as K + > 5.5 mEq/L) as opposed to 9.2% in the placebo group [ 26 ]. This effect occurred in a time-dependent manner.…”

“…Importantly, diuretic or sodium-glucose co-transporter-2 (SGLT2) inhibitor use reduced the risk of hyperkalemia. Despite the increase in serum K + , at 4 months, after routine K + monitoring and K + management strategies, the impact of increased hyperkalemia risk for any change from baseline was smaller with finerenone when compared with the placebo group [ 26 ].…”

Modifying chronic kidney disease progression with the mineralocorticoid receptor antagonist finerenone in patients with type 2 diabetes

“…47 Moreover, SGLT-2is also reduce the incidence of hyperkalaemia associated with finerenone in this trial. 85…”