Abstract Body (Do not enter title and authors here): Background
Finerenone significantly reduced the risk of CV and adverse kidney outcomes vs placebo in patients with CKD and T2D in FIDELITY, a prespecified pooled analysis of the phase III FIDELIO-DKD and FIGARO-DKD trials. Exposure to particulate matter air pollution ≤2.5 microns (PM_2.5) is established as the world’s leading environmental risk factor and is implicated in CV and kidney events. This FIDELITY post-hoc subanalysis aimed to examine the effect of finerenone across varying levels of PM_2.5 exposure.

Methods
Patients in FIDELITY were on optimized renin–angiotensin system inhibition and randomized 1:1 to finerenone or placebo. Key outcomes included composite CV (CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure), composite kidney (kidney failure, sustained ≥57% decrease in estimated glomerular filtration rate from baseline over at least 4 weeks, or kidney-related death), and combined composite CV and kidney. Participants were assigned to antecedent PM_2.5 exposure using site location at the time of enrollment (annual PM_2.5 using an integrated exposure model). The effect of finerenone vs placebo was assessed on outcomes across strata of PM_2.5 exposure (quartiles, ≤ vs > median) and as a continuous variable.

Results
A total of 12,990 participants were included. Median PM_2.5 exposure was 15.5 (IQR 9.8–21.0) µg/m³. PM_2.5 exposure was associated with higher CV and kidney event rates (Fig 1). Although finerenone had a similar beneficial impact on composite CV and renal outcomes across strata of PM_2.5 exposure (P_interaction=NS), the numbers needed to treat to prevent one composite CV/kidney event were 34 and 29 for participants at low (≤ median) and high (> median) PM_2.5 exposure, respectively. The finerenone safety profile was generally similar across PM_2.5 quartiles.

Conclusions
In FIDELITY, finerenone lowered the risks of CV and kidney outcomes vs placebo in patients with CKD and T2D irrespective of PM_2.5 exposure levels. Given the association between PM_2.5 and risk of CV and kidney events, finerenone may be particularly beneficial in those exposed to higher air pollution levels.