POS-829 Incidence and predictors of hyperkalaemia in patients with CKD and T2D in the FIDELIO-DKD trial

Abstract

Introduction: Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) have an increased risk of hyperkalaemia. Finerenone, a novel, selective, nonsteroidal, mineralocorticoid receptor antagonist, reduced the incidence of kidney and cardiovascular events in patients with CKD and T2D in the FIDELIO-DKD trial. This post hoc analysis describes the incidence and predictors of hyperkalaemia in FIDELIO-DKD. Methods: FIDELIO-DKD was a phase III, multicentre, double-blind trial that randomised 5734 patients (1:1) to finerenone or placebo. Patients with CKD, T2D and serum potassium ([K+]) ≤4.8 mmol/l at the run-in and screening visits, and treated with optimised renin–angiotensin system blockade were included. CKD was defined as a urine albumin-to-creatinine ratio (UACR) ≥30–<5000 mg/g and an estimated glomerular filtration rate (eGFR) ≥25–<75 ml/min/1.73 m2. Initial dosing of study drug (10 mg or 20 mg once daily [od]) was based on eGFR at screening. During the trial, study drug dosing was based on serum [K+] levels and eGFR changes, which were monitored at every study visit; the study drug was temporarily withheld if [K+] >5.5 mmol/l and restarted at 10 mg od when [K+] ≤5.0 mmol/l. In this safety analysis, hyperkalaemia was defined as an investigator-reported adverse event (AE) or by serum [K+] levels (>5.5 and >6.0 mmol/l); events were considered treatment-emergent if they occurred after the start of study drug administration and until 3 days after any interruption of study drug. Multivariate Cox proportional hazards regression was used to examine associations between baseline characteristics and first post-baseline treatment-emergent [K+] >5.5 or >6.0 mmol/l, adjusting for treatment assignment and baseline covariates chosen a priori based on clinical factors known to affect serum [K+]. A p‑value <0.05 was used to determine a significant association. Results: At baseline, 769/5658 (13.6%) and 390/5658 (6.9%) patients had [K+] >4.8 mmol/l and >5.0 mmol/l, respectively. After a median follow-up of 2.6 years, 44/2827 (1.6%) patients in the finerenone group and 12/2831 (0.4%) patients in the placebo group experienced a treatment-emergent hyperkalaemia-related serious AE. In the finerenone group, 64/2827 (2.3%) patients permanently discontinued the study drug due to hyperkalaemia, compared with 25/2831 (0.9%) patients in the placebo group. In total, 597/2785 (21.4%) and 256/2775 (9.2%) patients in the finerenone and placebo groups, respectively, had a treatment-emergent [K+] >5.5 mmol/l, while 126/2802 (4.5%) and 38/2796 (1.4%) patients, respectively, had a treatment-emergent [K+] >6.0 mmol/l. Selected baseline characteristics of patients with vs without any [K+] >5.5 or >6.0 mmol/l during the study are shown in the Table. The results of a multivariate analysis of hyperkalaemia risk factors will be presented. Conclusions: The K+ management protocol implemented in FIDELIO-DKD minimised the clinical impact of hyperkalaemia, as demonstrated by the low frequency of clinically meaningful hyperkalaemia-related serious AEs.