FINERENONE IN CHRONIC KIDNEY DISEASE AND TYPE 2 DIABETES: A FIDELITY ANALYSIS OF LEFT VENTRICULAR HYPERTROPHY

Therapeutic Area: Kidney Disease Background: Left ventricular hypertrophy (LVH) is a predictor of cardiovascular (CV) disease and associated morbidity and mortality. Patients with chronic kidney disease (CKD), type 2 diabetes (T2D) have a higher prevalence of LVH. In this exploratory analysis we investigated the effect of baseline LVH on cardiovascular and renal outcomes from FIDELITY, a pooled dataset from two phase III multicentre, double-blind trials of patients with CKD and T2D (FIDELIO-DKD and FIGARO-DKD). Methods: Patients in FIDELITY were treated with the maximum tolerated labelled dose of a renin–angiotensin system inhibitor (RASi) and randomized 1:1 to finerenone or placebo. LVH at baseline was determined based on coded electrocardiogram findings. Efficacy outcomes included a composite of CV death, non-fatal myocardial infarction (MI), non-fatal stroke, or hospitalization for heart failure (HFF), and a composite of kidney failure, a sustained ≥57% decrease in estimated glomerular filtration rate from baseline over ≥4 weeks, or renal death. Safety was also assessed. Results: Notable differences in demographics and baseline characteristics included higher systolic blood pressure and urine albumin-to-creatinine ratio in patients with LVH vs those without. Finerenone consistently reduced the relative risk of the CV composite outcome in patients with and without LVH (reduction of 28% vs 11%, respectively; p-value for interaction 0.11; Figure). The relative risk of HHF was reduced in both patient subgroups (66% reduction in patients with LVH vs 14% without LVH), with the effect of finerenone being significantly greater in patients with LVH (p-value for interaction 0.0024). Overall safety was similar between subgroups. The incidence of hyperkalaemia was higher with finerenone vs placebo irrespective of baseline LVH status, however discontinuation due to hyperkalaemia remained low in both groups. Conclusions: In this exploratory analysis, finerenone, in addition to standard of care with a RASi, reduced the overall risk of CV and kidney outcomes in patients with CKD and T2D with or without LVH at baseline. Furthermore, the effect of finerenone in reducing the incidence of HHF appeared to be more pronounced in patients with LVH than in those without.