A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease

Abstract

AimsTo 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.Methods and resultsMiner 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.ConclusionFinerenone 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.

A Randomized Controlled Study of Finerenone vs. Eplerenone in Japanese Patients With Worsening Chronic Heart Failure and Diabetes and/or Chronic Kidney Disease

“…14 Furthermore, the international phase 2b trial ARTSHeart Failure (ARTS-HF) in patients with worsening CHF and T2DM and/or CKD showed that finerenone was well tolerated and the proportion of patients with a decrease in N-terminal pro-BNP (NT-proBNP) of 30% from baseline to day 90 was similar in the finerenone groups to that in the eplerenone group. 15 The international phase 2b ARTS-Diabetic Nephropathy (ARTS-DN) conducted in patients with diabetic kidney disease showed that finerenone therapy led to improvements in the urinary-albumin-creatinine ratio, with a similar safety profile as placebo. 16 Based on the international ARTS-HF, the ARTS-HF Japan (Clinicaltrials.gov Identifier: NCT01955694) was designed to investigate the safety and efficacy of 5 treatment regimens of once-daily (o.d.)…”

“…The design of ARTS-HF Japan is based on that of the international ARTS-HF, which was the first clinical trial to investigate the novel nonsteroidal MRA finerenone in comparison with eplerenone in patients with worsening HFrEF requiring emergency treatment and who also had T2DM and/or CKD. 15 This will allow data from the 2 studies to be pooled for further analyses.…”

Diabetes and Hypertension: A Position Statement by the American Diabetes Association

“…MRAs also reduce albuminuria and have additional cardiovascular benefits (107)(108)(109)(110) (112). A Cochrane systematic review did not find conclusive evidence for or against blood pressure treatment for mild to moderate preexisting hypertension to reduce the risk of preeclampsia, preterm birth, small-for-gestational-age infants, or fetal death (113).…”

Rationale and design of the AdaptResponse trial: a prospective randomized study of cardiac resynchronization therapy with preferential adaptive left ventricular‐only pacing

“…diuretics. The reason for this choice is that the incidence rate of HF hospitalizations has decreased over the years due to advances in the treatment of HF, and the fact that there are geographic differences in the treatment of HF and the definition of hospitalization that led to different rates of HF hospitalization 34, 35, 36. The broader definition is intended to ensure that the event rate is high enough to have an achievable sample size and to accommodate geographic differences due to differing health care systems.…”