title: A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease.
abstract: To evaluate oral doses of the non-steroidal mineralocorticoid receptor antagonist finerenone given for 90 days in patients with worsening heart failure and reduced ejection fraction and chronic kidney disease and/or diabetes mellitus.
  
  
  
  Miner Alocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF) was a randomized, double-blind, phase 2b multicentre study (ClinicalTrials.gov: NCT01807221). Of 1286 screened patients, 1066 were randomized. Patients received oral, once-daily finerenone (2.5, 5, 7.5, 10, or 15 mg, uptitrated to 5, 10, 15, 20, or 20 mg, respectively, on Day 30) or eplerenone (25 mg every other day, increased to 25 mg once daily on Day 30, and to 50 mg once daily on Day 60) for 90 days. The primary endpoint was the percentage of individuals with a decrease of >30% in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline to Day 90. A key exploratory endpoint was a composite clinical endpoint of death from any cause, cardiovascular hospitalizations, or emergency presentation for worsening HF until Day 90. Mean age ranged from 69.2 to 72.5 years in different treatment groups (standard deviation 9.7-10.6 years). Decreases in NT-proBNP of >30% from baseline occurred in 37.2% of patients in the eplerenone group and 30.9, 32.5, 37.3, 38.8, and 34.2% in the 2.5→5, 5→10, 7.5→15, 10→20, and 15→20 mg finerenone groups, respectively (P = 0.42-0.88). Except for the 2.5→5 mg finerenone group, the composite clinical endpoint occurred numerically less frequently in finerenone-treated patients compared with eplerenone; this difference reached nominal statistical significance in the 10→20 mg group (hazard ratio 0.56, 95% confidence interval, CI, 0.35; 0.90; nominal P = 0.02), despite the fact that this phase 2 study was not designed to detect statistical significant differences. A potassium level increase to ≥5.6 mmol/L at any time point occurred in 4.3% of patients, with a balanced distribution among all treatment groups.
  
  
  
  Finerenone was well tolerated and induced a 30% or greater decrease in NT-proBNP levels in a similar proportion of patients to eplerenone. The finding of reduced clinical events in the finerenone 10→20 mg group should be further explored in a large outcomes trial.
authors.affiliation: Department of Cardiology, National and Kapodistrian University of Athens, School of Medicine, Attikon University Hospital, Rimini 1, Haidari, Athens 12462, Greece geros@otenet.gr.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Filippatos
authors.affiliation: Department of Innovative Clinical Trials, University Medical Centre Gottingen, Gottingen, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: Universitatsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
authors.affiliation: Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.affiliation: Centre of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.affiliation: Research Centre of the Italian Association of Hospital Cardiologists, Florence, Italy.
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.affiliation: Medical University, Clinical Military Hospital, Wrocław, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.affiliation: University of Groningen, Groningen, Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: Inserm, CHU Department of Cardiology, Université de Lorraine, Nancy, France.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: Global Clinical Development, Bayer Pharma AG, Leverkusen, Germany.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Global Clinical Development, Bayer Pharma AG, Leverkusen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Nowack
authors.affiliation: Global Clinical Development, Bayer Plc, Newbury, UK.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Palombo
authors.affiliation: Heart Diseases Research, Global Drug Discovery, Bayer Pharma AG, Leverkusen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kolkhof
authors.affiliation: Global Research & Development Statistics, Bayer Pharma AG, Leverkusen, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Kimmeskamp-Kirschbaum
authors.affiliation: M.A.R.C.O. GmbH & Co. KG, Dusseldorf, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pieper
authors.affiliation: University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
mesh_terms: D000368:Aged; D002908:Chronic Disease; D003920:Diabetes Mellitus; D004311:Double-Blind Method; D000077545:Eplerenone; D006333:Heart Failure; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists; D020097:Natriuretic Peptide, Brain; D010446:Peptide Fragments; D051436:Renal Insufficiency, Chronic; D013148:Spironolactone / Q000031:analogs & derivatives
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D010446:Peptide Fragments; D020097:Natriuretic Peptide, Brain; D013148:Spironolactone; D000077545:Eplerenone
keywords: Finerenone; Mineralocorticoid receptor antagonists; Worsening heart failure