Finerenone and Cardiorenal Outcomes by History of Cardiovascular Disease in Patients with Type 2 Diabetes: Fidelity Analyses

Abstract

Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) are at risk of cardiovascular complications. FIDELITY (prespecified pooled analysis of FIDELIO-DKD [NCT02540993] and FIGARO-DKD [NCT02545049]) evaluated finerenone (a selective, nonsteroidal mineralocorticoid receptor antagonist) in patients with CKD and T2D. Cardiovascular and kidney outcomes were compared in primary and secondary prevention populations. Patients with T2D, and either urine albumin-to-creatinine ratio (UACR [mg/g])≥30–<300 and estimated glomerular filtration rate (eGFR [mL/min/1.73m2])≥25–≤90, or UACR≥300–≤5,000 and eGFR≥25, treated with optimized renin–angiotensin system blockade, were randomized to finerenone or placebo. Cardiovascular outcomes (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or heart failure hospitalization) and kidney outcomes (kidney failure, sustained eGFR decrease≥57% or kidney death) were categorized by prior atherosclerotic cardiovascular disease (CVD). Investigator-reported adverse events (AEs) were assessed. 5,935/13,026 of eligible patients had a history of CVD. Finerenone lowered the risk of the cardiovascular outcome vs placebo (HR=0.86; 95%CI=0.78-0.95; 3.0-year median follow-up), with no treatment modification by CVD history (HR=0.83 [95%CI=0.74-0.94] in patients with CVD; HR=0.91 [95%CI=0.78-1.06] in patients without CVD; Pinteraction=0.375). The effect of finerenone on the kidney outcome (HR=0.77; 95%CI=0.67-0.88) was not modified by CVD (HR=0.71 [95%CI=0.57-0.88] and HR=0.81 [95%CI=0.68-0.97] in patients with and without CVD history, respectively; Pinteraction=0.325). AEs did not differ between CVD subgroups, with a low incidence of hyperkalemia-related treatment discontinuation that was more frequent in the finerenone group but similar between CVD subgroups. Finerenone reduced the risk of cardiovascular and kidney outcomes in patients with CKD and T2D vs placebo, irrespective of CVD history.