Safety and Short-Term Effects of Empagliflozin in Patients with Heart Failure and End-Stage Renal Disease.

Aim: Our aim was to evaluate the safety of empagliflozin in escalating doses among patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis who also have heart failure.

Methods: This single-arm, open-label, dose-escalation study enrolled patients with ESRD on maintenance hemodialysis with heart failure (reduced or preserved ejection fraction) from June to September 2023. Patients sequentially received empagliflozin at doses of 5 mg, 10 mg, and 25 mg daily for 4 weeks per dose, alongside standard care. Pre-dialysis vital signs, electrocardiograms, complete blood counts, and biochemical profiles were monitored weekly. Dose-dependent changes were assessed using linear mixed models.

Results: A total of 17 patients participated, without significant adverse events. Empagliflozin treatment was associated with a significant shortening of QRS duration (regression coefficient - 3.35 ms, P < 0.001), stable QT intervals, increased serum calcium (regression coefficient 0.02 mg/dL, P = 0.004), and decreased bicarbonate levels (regression coefficient - 0.27 mmol/L, P = 0.019). Additionally, diastolic blood pressures measured pre-dialysis significantly increased over time (regression coefficient 1.70 mmHg, P = 0.025).

Conclusion: Empagliflozin at doses of 5 mg, 10 mg, and 25 mg per day, administered sequentially for 4 weeks each, demonstrated a favorable safety profile in patients with ESRD undergoing maintenance hemodialysis. Further studies are warranted to explore clinical implications of the observed physiological changes.

Registration: This was a single-arm, open-label, dose-escalating safety study required by the institutional review board of the National Taiwan University Hospital before the commencement of two randomized controlled trials registered at ClinicalTrials.gov (EMPA-PRED [NCT06249945] and EMPA-RRED [NCT06249932]).