Finerenone and Heart Failure Outcomes by Kidney Function/Albuminuria in Chronic Kidney Disease and Diabetes

Abstract

Background: In patients with type 2 diabetes (T2D), risks of cardiovascular mortality and heart failure (HF) increase with decreasing kidney function (estimated glomerular filtration rate [eGFR]) and increasing albuminuria (urine albumin-to-creatinine ratio [UACR]). Finerenone, a selective, nonsteroidal mineralocorticoid receptor antagonist, improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and T2D in FIDELITY (Finerenone in Chronic Kidney Disease and Type 2 Diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial Programme Analysis).

Objectives: This study sought to evaluate the effects of finerenone on HF outcomes by eGFR and/or UACR categories.

Methods: FIDELITY included 13,026 patients with T2D and CKD (UACR 30-5,000 mg/g and eGFR ≥25 mL/min/1.73 m2) randomized to finerenone or placebo. Time-to-event outcomes were first hospitalization for heart failure (HHF), cardiovascular death or first HHF, recurrent HHF, and cardiovascular death or recurrent HHF, analyzed in subgroups by baseline eGFR (<60 and ≥60 mL/min/1.73 m2) and/or UACR (<300 and ≥300 mg/g).

Results: Compared with placebo, finerenone significantly reduced risk of first HHF (HR: 0.78 [95% CI: 0.66-0.92]; P = 0.003), cardiovascular death or first HHF (HR: 0.83 [95% CI: 0.74-0.93]; P = 0.002), recurrent HHF (HR: 0.79 [95% CI: 0.64-0.96]; P = 0.021), and cardiovascular death or recurrent HHF (HR: 0.82 [95% CI: 0.72-0.95]; P = 0.006). The risk of outcomes increased across baseline eGFR and UACR categories; lowest incidences were seen in patients with an eGFR ≥60 mL/min/1.73 m2 and a UACR <300 mg/g. Finerenone improved HF outcomes irrespective of baseline eGFR and/or UACR categories (all P interaction values >0.10).

Conclusions: Compared with placebo, finerenone improved HF-related outcomes in patients with CKD and T2D, with consistent benefits across eGFR and/or UACR categories. (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD], NCT02540993; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Chronic Kidney Disease [FIGARO-DKD], NCT02545049).

Keywords: albuminuria; chronic kidney disease; estimated glomerular filtration rate; finerenone; heart failure; mineralocorticoid receptor antagonist.

Conflict of interest statement

Funding Support and Author Disclosures The Executive Committee designed the studies in conjunction with Bayer AG. Bayer AG participated in data collection, data analysis, data interpretation, and approval of the manuscript. This work was supported by Bayer AG, who funded the FIDELIO-DKD and FIGARO-DKD trials and combined FIDELITY analysis. Dr Filippatos has served as a committee member of trials and registries sponsored by Amgen, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor Pharma; as a senior consulting editor for JACC: Heart Failure; and received research support from the European Union. Dr Anker has received research support from Abbott Vascular and Vifor International; and personal fees from Abbott Vascular, Bayer, Boehringer Ingelheim, BRAHMS, Cardiac Dimensions, Impulse Dynamics, Novartis, Servier, and Vifor Pharma. Dr Pitt has received consultant fees from AstraZeneca, Bayer, Boehringer Ingelheim, Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, KBP Biosciences, PhaseBio, Proton Intel, Sanofi/Lexicon, Sarfez, scPharmaceuticals, SQ Innovation, Tricida, and Vifor/Relypsa; owns stock options in KBP Biosciences, Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, Proton Intel, Sarfez, scPharmaceuticals, SQ Innovation, Tricida, Vifor/Relypsa; and holds a patent for site-specific delivery of eplerenone to the myocardium (U.S. Patent No. 9931412) and a provisional patent for histone-acetylation-modulating agents for the treatment and prevention of organ injury (provisional patent; U.S. Patent No. 63/045,784). Dr Rossing has received personal fees from Bayer during the conduct of the study (all fees given to Steno Diabetes Center Copenhagen); research support and personal fees from AstraZeneca and Novo Nordisk (all fees given to Steno Diabetes Center Copenhagen); and personal fees from Astellas, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, Sanofi, and Vifor (all fees given to Steno Diabetes Center Copenhagen). Dr Joseph was a full-time employee of Bayer AG (Division of Pharmaceuticals) at the time of the studies and analysis; he is now a full-time employee of Chiesi Farmaceuitici S.p.A, Parma, Italy. Dr Kolkhof is a full-time employee of Bayer AG (Division of Pharmaceuticals); and is the co-inventor of finerenone and holds U.S. and European patents relating to finerenone (U.S. Patent No. 8436180B2 and European Patent No. 2132206B1). Mr Lambelet is an external employee of Bayer AG (Division of Pharmaceuticals). Dr Lawatscheck is a full-time employee of Bayer AG (Division of Pharmaceuticals). Dr Bakris has received research funding, paid to the University of Chicago Medicine, from Bayer during the conduct of the study; received research funding, paid to the University of Chicago Medicine, from Novo Nordisk and Vascular Dynamics; served as a consultant for and received personal fees from Alnylam, Merck, and Relypsa; is an editor of the American Journal of Nephrology, Nephrology, and Hypertension; is a section editor of UpToDate; and is an associate editor of Diabetes Care and Hypertension Research. Dr Ruilope has received consulting fees from Bayer. Dr Agarwal has received personal fees and nonfinancial support from Bayer Healthcare Pharmaceuticals Inc during the conduct of the study; received personal fees and nonfinancial support from Akebia Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Fresenius, Janssen, Relypsa, Sanofi, and Vifor Pharma; received personal fees from Ironwood Pharmaceuticals, Lexicon, Merck & Co, and Reata; received nonfinancial support from E.R. Squibb & Sons, Opko Pharmaceuticals, and Otsuka America Pharmaceutical; served as a member of data safety monitoring committees for Amgen, AstraZeneca, and Celgene; served as a member of steering committees of randomized trials for Akebia Therapeutics, Bayer, Janssen, and Relypsa; served as a member of adjudication committees for AbbVie, Bayer, Boehringer Ingelheim, and Janssen; served as associate editor of the American Journal of Nephrology and Nephrology Dialysis and Transplantation; served as an author for UpToDate; and received research grants from the U.S. Veterans Administration and the National Institutes of Health.

Copyright © 2022. Published by Elsevier Inc.