Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study‐Heart Failure (ARTS‐HF): a randomized study of finerenone vs. eplerenone in patients who have worsening chronic heart failure with diabetes and/or chronic kidney disease

Abstract

Aims To investigate the safety and potential efficacy of the novel non‐steroidal mineralocorticoid receptor antagonist finerenone in patients with worsening chronic heart failure and reduced left ventricular ejection fraction (HFrEF) and at high risk of hyperkalaemia and worsening renal dysfunction. Methods and results The MinerAlocorticoid Receptor antagonist Tolerability Study‐Heart Failure (ARTS‐HF; NCT01807221) is a multicentre, randomized, double‐blind, active‐comparator‐controlled, six‐parallel‐group, phase 2b dose‐finding study. In total, 1060 patients with HFrEF and concomitant type 2 diabetes mellitus and/or chronic kidney disease (CKD) will be randomized within 7 days of emergency presentation to hospital for worsening chronic HF to receive finerenone (one of five doses in the range 2.5–20.0 mg once daily) or eplerenone (25 mg every second day to 50 mg once daily for 90 days). The primary objective is to investigate the safety and potential efficacy (measured as the percentage of individuals with a decrease in plasma N‐terminal pro‐B‐type natriuretic peptide [NT‐proBNP] of more than 30% relative to baseline at day 90 ± 2) of different oral doses of finerenone compared with eplerenone. Other objectives are to assess the effects of finerenone on a composite clinical endpoint (death from any cause, cardiovascular hospitalizations, or emergency presentations for worsening chronic HF), and on changes in health‐related quality of life from baseline. Conclusions ARTS‐HF is the first phase 2b clinical trial to investigate the effects of finerenone on plasma NT‐proBNP in a high‐risk population of patients who have worsening chronic HF with type 2 diabetes mellitus and/or CKD presenting at the emergency department.

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

“…The design of ARTS-HF Japan is based on the design of the international ARTS-HF, 17 and was a randomized, doubleblind, active-comparator-controlled, parallel-group, phase 2b, dose-finding study conducted at 31 centers in Japan. The study protocol was developed by the sponsor (Bayer Yakuhin Ltd), and was approved by independent ethics committees and/or institutional review boards for all participating centers before the study began.…”

Newer drugs for heart failure: hype or hope?

“…The authors then discuss finerenone the nonsteroidal mineralocorticoid receptor antagonist that has superior cardiac selectivity as compared to spironolactone and eplerenone. The ARTS study [14] confirmed the association of finerenone with a lower increase in serum potassium compared to spironolactone in patients with mild to moderate chronic kidney disease. The subsequently completed larger ARTS-HF trial in patients with diabetes and or mild to moderate kidney disease that compared finerenone to eplerenone showed promising results that included reduction of all secondary end points including CV hospitalization, CV death and total mortality.…”

Hyperkalemia in heart failure patients: current challenges and future prospects

“…No significant differences were found in the main objective (30% decrease of NT-proBNP levels), or in safety (same incidence of potassium .5.6 mEq/L with both drugs, 4.3%). 69 An improvement was observed in most of the secondary objectives (cardiovascular hospitalization, cardiovascular mortality, and mortality for any other reason; hazard ratio [HR] 0.56; P=0.0229), mainly in subgroups that received higher doses of finerenone (7.5 and 10 mg). For this reason, a new clinical trial has been designed (BAY 94-8862) 70 to evaluate the morbimortality as main objective in a similar population (diabetics or patients with stage III CKD) treated with high doses of finerenone.…”