Abstract 13298: Impact of Finerenone on Cardiac Biomarkers in Patients With T2D and Chronic Kidney Disease

Abstract

Introduction: Finerenone is a non-steroidal, selective antagonist of the mineralocorticoid receptor (MR), which blocks MR-mediated sodium reabsorption and MR overactivation. In this biomarker substudy to FIDELITY, a pooled, pre-specified analysis of FIGARO-DKD and FIDELIO-DKD, NT-proBNP and cardiac troponin T (cTnT) levels were assessed to explore the effect of finerenone on cardiac markers. FIGARO-DKD and FIDELIO-DKD were two phase III trials investigating efficacy and safety of finerenone vs. placebo (PLC) on cardiorenal outcomes, in patients with T2D and CKD. Hypothesis: Finerenone impacts the levels of major cardiac biomarkers. Methods: Samples were collected prospectively from non-selected patients who consented to the biomarker study. At baseline (BL), this study included 1037 subjects with cTnT data and 1592 subjects with NT-proBNP data from 13 and 24 countries, respectively. Samples were analyzed at BL, 4, 12, 24, 36 and 48 months follow-up on treatment with finerenone or PLC. Treatment effects on biomarkers were computed by a linear mixed model, adjusted for age, gender, screening eGFR and UACR, history of CVD, BL biomarker levels and geographical region. Results: Both, NT-proBNP and cTnT increased over time in both arms, yet, the increase was significantly lower in the active arm compared to PLC, even though finerenone temporarily reduces eGFR. The maximum ratio (finerenone to PLC) was 0.82 (95% CI: 0.76 to 0.90) at month 4 for NT-proBNP, and 0.94 (95% CI: 0.892 to 0.995) for cTnT at month 36. Median levels of biomarkers at BL were 177 pg/mL (NT-proBNP, IQR: 74-426) or 18 pg/mL (cTnI, IQR: 7-27). Conclusions: In patients with T2D and CKD, finerenone, on top of maximum tolerated labelled RAS inhibition and standard of care co-medication, reduced plasma NT-proBNP and cTnT, biomarkers usually associated with cardiac stress and injury, and indicative of poor prognosis. Our findings are in line with outcome data from FIDELITY showing a 22% risk reduction for HF hospitalization1 and other findings suggestive of reduced adverse cardiac remodeling. This data provides supportive mechanistic insights for benefits on cardiorenal outcomes in FIDELITY, confirming preclinical findings as well as clinical data on short-term treatment effects on NT-proBNP.