ADA 2022: The protective effect of finerenone on cardiovascular and renal outcomes was not affected by initial HbA1c levels or T2D duration in analysis of data from the FIDELITY pooled cohort.
Reductions seen in risk for cardiovascular (CV) and renal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) treated with finerenone were consistent across baseline A1c, variability in A1c, and duration of T2D, according to findings of FIDELITY, a prespecified pooled analysis of the FIDELIO-DKD and FIGARO-DKD clinical trials.
FIDELITY researchers also reported, however, that variability in HbA1c during the study period was associated with greater risk of negative cardiorenal outcomes.
The findings were presented by Janet B. McGill, MD, professor of medicine, division of endocrinology, metabolism, and lipid research, Washington University School of Medicine, at the 82nd Scientific sessions of the American Diabetes Association, held in New Orleans, June 3-7, 2022.
The novel nonsteroidal mineralocorticoid receptor antagonist finerenone was found in 2 landmark clinical trials to slow progression of kidney disease and improve CV outcome in patients with advanced kidney disease and T2D (FIDELIO-DKD) and to reduce the risk of CV outcomes in a broader population of patients with less severe kidney disease and T2D (FIGARO-DKD).
In the FIDELITY prespecified analysis of pooled data from both trials, investigators found that finerenone reduced cardiorenal outcomes across both cohorts without affecting HbA1c.
The current FIDELITY analysis was designed to further evaluate the efficacy of finerenone across a wide spectrum of patients with CKD and T2D by examining the drug’s effect by baseline HbA1c, HbA1c variability, and diabetes duration.
FIDELIO-DKD and FIGARO-DKD were of similar design and randomized patients with T2D and CKD (UACR across studies ≥30-≤5000 mg/g and eGFR ≥25 mL/min/1.73 m2) in 1:1 fashion to finerenone or placebo.
In this analysis, effects of finerenone vs placebo on composite CV (CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney (kidney failure, sustained ≥57% eGFR decline from baseline, or renal death) outcomes were analyzed by baseline HbA1c quartiles, HbA1c variability (first year of treatment), and T2D duration quartiles.
The total pooled cohort for analysis included 13 026 patients with an average age of 65 years; the majority were men (69%) and White (68%). The mean baseline HbA1c was 7.7% and mean duration of T2D was 15.4 years. McGill and colleagues stratified participants by baseline quartiles of HbA1c and disease duration:
The researchers found that participants in higher baseline HbA1c quartiles had longer disease duration and also more diabetes-related complications, according to the study abstract. The urinary albumin/creatinine ratio also was higher in these patients and women were more likely than men to be in the higher baseline HbA1c quartiles.
Reductions in risk for the CV and kidney composite outcomes with finerenone vs placebo were consistent across quartiles of HbA1c (p-interaction 0.52 and 0.09, respectively) and diabetes duration (p-interaction 0.12 and 0.75).
McGill et al also report that HbA1c variability in the first year of treatment was associated with higher cardiorenal risks. Specifically, each 1 unit increase in mean absolute residual of HbA1c was associated with a 20% increased risk of a CV event (HR 1.20; 95% CI 1.07-1.35; p=.0016) and a 36% increased risk of a kidney event (HR 1.36; 95% CI 1.21-1.52; p<.001).
The CV and kidney benefits of finerenone, however, were sustained despite variability in HbA1c. While investigators observed that finerenone treatment was associated with a difference in probability of events at 3.5 years for cardiorenal outcomes, the difference did not reach statistical significance (P-interaction, 0.48 and 0.09, respectively).
The investigators’ safety analysis found the overall incidence of treatment-emergent adverse events similar between the finerenone and placebo groups across baseline HbA1c and diabetes duration quartiles.
The incidence of treatment-emergent hyperkalemia, they reported, was higher in finerenone-treated patients than in those treated with placebo and highest in patients with longest duration of diabetes.
Reference: McGill JB, Agarwal R, Ankder S, et al. Effects of finerenone in patienst with CKD and T2D are independent of HbA1c at baseline, HbA1c variability, and duration of diabetes. Diabetes 2022;71(Supplement_1):16-LB.