407-P: Efficacy of Finerenone in Patients with Abnormal Markers of Liver Steatosis and Fibrosis—A FIDELITY Subgroup Analysis
NIKOLAOS PERAKAKIS, STEFAN R. BORNSTEIN, ANDREAS L. BIRKENFELD, ANDREAS LINKERMANN, STEFAN ANKER, GERASIMOS FILIPPATOS, BERTRAM PITT, PETER ROSSING, LUIS M. RUILOPE, PETER KOLKHOF, ROBERT LAWATSCHECK, CHARLIE SCOTT, GEORGE BAKRIS- Endocrinology, Diabetes and Metabolism
- Internal Medicine
Introduction: Finerenone, a selective, nonsteroidal mineralocorticoid receptor antagonist, showed cardiorenal benefits vs placebo in patients with chronic kidney disease and type 2 diabetes. Here, we analyzed patients with liver function abnormalities in FIDELITY, a prespecified pooled dataset from the FIDELIO-DKD and FIGARO-DKD trials.
Methods: Patients with urine albumin-to-creatinine ratio ≥30-≤5000 mg/g and estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 and type 2 diabetes were analyzed according to elevated transaminases, high risk of steatosis (hepatic steatosis index [HSI] >36), and risk of intermediate to advanced fibrosis (Fibrosis-4 Index [FIB-4] scores >1.30, >2.67, and >3.25). Changes in liver function and in kidney (kidney failure, sustained 57% eGFR decline, or renal death) and cardiovascular (CV; CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite outcomes were assessed.
Results: Across 13,026 patients, finerenone reduced the risk of kidney and CV outcomes compared with placebo in patients with elevated transaminases (HR=0.75; 95% CI 0.50-1.13 and HR=0.81; 95% CI 0.62-1.07, respectively), at high risk of steatosis (HR=0.75; 95% CI 0.64-0.88 and HR=0.85; 95% CI 0.77-0.95, respectively), and at high risk of intermediate fibrosis (HR=0.75; 95% CI 0.60-0.93 and HR=0.76; 95% CI 0.67-0.87, respectively), with stronger reductions in the risk of the CV composite outcome at higher FIB-4 scores (HR=0.61; 95% CI 0.41-0.92; p-value for interaction=0.13 and HR=0.48; 95% CI 0.25-0.90; p-value for interaction=0.03 for FIB-4 >2.67 and >3.25, respectively). Liver transaminase levels remained consistent between treatment groups throughout the study.
Conclusions: Finerenone demonstrated robust and consistent cardiorenal benefits in patients with abnormal liver function and even more profound CV benefits in patients with higher FIB-4 scores.
Disclosure
N.Perakakis: Advisory Panel; Bayer Inc., Other Relationship; Novo Nordisk, Novo Nordisk. P.Kolkhof: Employee; BAYER AG. R.Lawatscheck: Employee; Bayer Inc. C.Scott: None. G.Bakris: Advisory Panel; Janssen Pharmaceuticals, Inc., Consultant; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Other Relationship; Bayer Inc. S.R.Bornstein: None. A.L.Birkenfeld: None. A.Linkermann: None. S.Anker: Advisory Panel; AstraZeneca, Novartis AG, Consultant; Bayer Inc., Boehringer Ingelheim Pharma GmbH&Co.KG, Vifor Pharma Management Ltd., Research Support; Abbott, Vifor Pharma Management Ltd. G.Filippatos: Other Relationship; Boehringer-Ingelheim, Bayer Inc., Amgen Inc., Medtronic, Vifor Pharma Management Ltd., Novartis, Servier Laboratories. B.Pitt: Consultant; Bayer Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Vifor Pharma Management Ltd., Lexicon Pharmaceuticals, Inc., PhaseBio Pharmaceuticals, Inc., KBP Bioscience, Merck & Co., Inc. P.Rossing: Other Relationship; Abbott Diagnostics, AstraZeneca, Bayer Inc., Boehringer Ingelheim Inc., Novo Nordisk, Merck KGaA, Gilead Sciences, Inc., Sanofi. L.M.Ruilope: Advisory Panel; Bayer Inc.