Efficacy and safety of finerenone in patients with chronic kidney disease and type 2 diabetes by diuretic use: A FIDELITY analysis

Presented at the ESC congress 2023 by: Robert Mentz, MD - Durham, NC, USA

Introduction and methods

Thiazide and loop diuretics are commonly used to treat hypertension and volume overload in patients with CKD. However, diuretics may induce potassium loss, which is associated with poor CV outcomes. In addition, the use and dose of diuretics serve as a marker of disease severity, and diuretic requirement is potentially also a marker and mediator of adverse outcomes.

Previously, the FIDELITY (FInerenone in chronic kiDney diseasE and type 2 diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial programme analYsis) analysis showed the selective nonsteroidal MRA finerenone improved CV outcomes and slowed CKD progression compared with placebo in patients with CKD and T2D. In the current post-hoc exploratory analysis of the FIDELITY dataset, the efficacy and safety of finerenone were assessed by baseline diuretic use.

FIDELITY is a prespecified, individual patient-level data pooled analysis of 2 phase 3 trials: FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease; n=5674) and FIGARO-DKD (Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease; n=7352). In these RCTs, patients with CKD and T2D on maximally tolerated RAASi therapy were randomized to finerenone (10 or 20 mg once daily based on eGFR at screening visit) or placebo. Eligibility criteria included serum potassium ≤4.8 mmol/L. Median follow-up duration was 3 years. At baseline, 51.5% of the 13,026 patients were treated with diuretics at baseline, of whom 41.8% were on loop diuretics and 47.0% were on thiazide diuretics.

Outcomes of the current analysis were: (1) composite CV outcome, consisting of time to CV death, nonfatal MI, nonfatal stroke, or hospitalization for HF; (2) treatment-emergent hypokalemia; and (3) safety events, including hyperkalemia.

Main results

• Finerenone reduced the risk of the composite CV outcome compared with placebo in patients treated with diuretics at baseline (HR: 0.86; 95%CI: 0.77–0.97) and those without diuretics (HR: 0.86; 95%CI: 0.74–1.00; P for interaction=0.95).
• Diuretic dose also did not influence treatment effect of finerenone versus placebo (HR for low-dose diuretics: 0.84; 95%CI: 0.72–0.99; HR for high-dose diuretics: 0.90; 95%CI: 0.74–1.09; P for interaction across no, low-dose, and high-dose diuretics groups=0.88).
• On-treatment sensitivity analysis showed modification by diuretic use during the study, with generally lower incidence rates of the composite CV outcome in the finerenone and placebo groups observed in patients without concomitant diuretic therapy compared with those with concomitant diuretic use.
• Compared with placebo, finerenone reduced the risk of treatment-emergent hypokalemia was reduced in patients treated with diuretics (relative risk (RR): 0.6; 95%: 0.4–0.8) and those without diuretics (RR: 0.7; 95%: 0.5–0.9).
• The incidences of adverse events and serious adverse events were similar between the study arms and between patients with and without diuretics.
• The incidence of hyperkalemia was higher with finerenone compared with placebo, regardless of diuretic use. However, the incidence of hyperkalemia leading to hospitalization or permanent discontinuation of the study drug was low in all treatment groups.

Conclusion

This post-hoc exploratory analysis of the FIDELITY dataset showed that finerenone reduced the risk of CV outcomes compared with placebo in patients with CKD and T2D irrespective of baseline diuretic use or dose. In addition, finerenone reduced the risk of treatment-emergent hypokalemia in both patients with and without diuretics. The incidence of treatment-emergent adverse events was also not influenced by diuretic use.

• Our reporting is based on the information provided at the ESC Congress -