Effect of finerenone in patients with chronic kidney disease and type 2 diabetes by baseline anaemia status: a FIDELITY analysis

Abstract Introduction Anaemia is a common complication affecting ∼42% patients with chronic kidney disease (CKD) stages 3–5 at 1 year after diagnosis and ∼67% at 5 years, with prevalence increasing as estimated glomerular filtration rate (eGFR) decreases. Despite the fact that anaemia is associated with CKD progression, adverse cardiovascular (CV) events and premature mortality in patients with CKD, management of these patients remains suboptimal. The nonsteroidal mineralocorticoid receptor antagonist finerenone demonstrated significant cardiorenal benefits in patients with CKD and type 2 diabetes (T2D) in FIDELITY (a prespecified pooled analysis of the phase III FIDELIO-DKD and FIGARO-DKD trials). However, the effect of anaemia on CV and kidney outcomes in patients receiving finerenone has not been established. Purpose This post hoc analysis investigated the treatment effects and safety of finerenone vs placebo in patients categorised by baseline anaemia status. Methods Eligible patients with CKD (urine albumin-to-creatinine ratio [UACR] ≥30–<300 mg/g and eGFR ≥25–≤90 ml/min/1.73 m² or UACR ≥300–≤5000 mg/g and eGFR ≥25 ml/min/1.73 m²) and T2D, and on optimised renin–angiotensin system inhibitor were randomised 1:1 to finerenone or placebo. Anaemia was defined using the World Health Organization criteria: serum haemoglobin levels <13 g/dl (male) or <12 g/dl (female) or treatment with an erythropoiesis-stimulating agent at baseline. Key outcomes analysed by baseline anaemia status included a CV composite (CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalisation for heart failure [HHF]) and kidney composite (kidney failure, sustained eGFR decrease ≥57%, or kidney-related death), HHF, and all-cause mortality. Safety outcomes were assessed by treatment-emergent adverse events. Results Of 13,007 patients, 4293 (33.0%) had anaemia at baseline. The risk reduction on the CV composite outcome was nominally significant with finerenone vs placebo in patients with anaemia at baseline but not in those without (p-value for interaction=0.04; Figure 1). Finerenone also reduced the risk of the kidney composite outcome vs placebo, with no heterogeneity between the treatment groups and across the anaemia subgroups (Figure 1). In addition, finerenone was associated with a reduced risk of all-cause mortality and HHF outcomes vs placebo, irrespective of baseline anaemia status (Figure 1). Incidence of treatment emergent hyperkalaemia was higher in patients with anaemia at baseline in both treatment arms (21.2% finerenone vs 11.5% placebo) compared to those without anaemia (10.5% finerenone vs 4.6% placebo). Conclusions In patients with CKD and T2D, anaemia was found to be a modifier to the effect of finerenone on the CV composite outcome. There was no heterogeneity of treatment effects with finerenone vs placebo, by anaemia at baseline, on kidney composite outcome, all-cause mortality and HHF.