Abstract / Summary
Aims: Exposure to particulate matter air pollution ≤2.5 µm (PM 2.5 ) is associated with cardiovascular (CV) and kidney morbidity and mortality. This post hoc analysis of FIDELITY, a prespecified pooled analysis of phase 3 randomized clinical trials (FIDELIO-DKD [NCT02540993], FIGARO-DKD [NCT02545049]), determined the impact of PM 2.5 exposure on CV and kidney events and the effects of finerenone on these outcomes across PM 2.5 exposures in patients with CKD and T2D. Methods: Patients with CKD and T2D on optimized renin–angiotensin system blockade were randomized 1:1 to finerenone or placebo. Key outcomes included composite CV outcomes (CV death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure); composite kidney outcomes (kidney failure, sustained ≥57 % decrease in eGFR, kidney-related death); combined composite CV and kidney outcomes; and safety. Outcomes were stratified by PM 2.5 exposure and patients grouped into quartiles of median PM 2.5 exposure with interquartile range as cutoffs. Results: Median PM 2.5 exposure was 15.5 µg/m 3 (N = 12 990). Increased PM 2.5 exposure was associated with higher occurrence of CV and kidney events. Finerenone reduced composite CV (hazard ratio [HR], 0.86; 95 % CI, 0.78–0.95), kidney (HR, 0.76; 95 % CI, 0.66–0.88) and combined CV and kidney (HR, 0.83; 95 % CI, 0.76–0.90) outcomes versus placebo across PM 2.5 exposures ( P interaction =0.37, 0.14, and 0.74, respectively). Proportions of adverse events (AEs) and serious AEs were generally balanced between treatment arms. Across PM 2.5 quartiles, hyperkalemia was more frequent with finerenone, but few led to hospitalization. Conclusions: Increased PM 2.5 exposure is associated with higher occurrence of CV and kidney events. Finerenone lowered the risk of CV and kidney events regardless of PM 2.5 exposure levels in patients with CKD and T2D.