New Heart Failure Drug Offers Increased End-Organ Protection

Finerenone, a new drug to reduce the risk for death from heart disease, was no more effective than the currently approved eplerenone in reducing the heart failure (HF) biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with heart disease and diabetes and/or chronic kidney disease. Results of the ARTS-HF trial presented at the European Society of Cardiology Congress 2015 showed that finerenone may, however, offer more effective end-organ protection than eplerenone.

“While finerenone was not superior for the primary outcome of our study, it was more effective than eplerenone for the secondary composite endpoint of death from any cause, cardiovascular hospitalizations, or emergency presentations for worsening HF,” said Gerasimos Filippatos, MD, of Athens University Hospital Attikon in Athens, Greece, in a press release.

The nonsteroidal mineralocorticoid receptor antagonists finerenone and eplerenone work by blocking the hormone aldosterone, thereby lowering the amount of sodium and water the body retains. This helps lower blood pressure to prevent stroke, kidney problems, and myocardial infarction. However, while eplerenone distributes greater to the kidneys, finerenone is highly cardio-selective and offers comparative protection to the heart and kidneys.

The ARTS-HF study (MinerAlocorticoid Receptor AnTagonist Study in Heart Failure) included 1055 participants with a mean age of 71 years who came to the emergency department for treatment of worsening HF and type 2 diabetes mellitus and/or chronic kidney disease.

Participants were randomly assigned to 6 drug treatment groups for 90 days. One group was assigned to eplerenone while the other 5 groups were assigned to different doses of finerenone.

Drug doses increased for all groups throughout the study period. Participants assigned to eplerenone started with a dose of 25 mg every other day and increased to 25 mg daily on day 30 and to 50 mg daily by day 60. The finerenone groups started with 2.5 mg, 5 mg, 7.5 mg, 10 mg, and 15 mg daily and increased to 5 mg, 10 mg, 15 mg, 20 mg, and 20 mg, respectively, by day 30, provided that their blood potassium levels remained at or below 5.0 m mol/L.

The study’s primary endpoint was the percentage of participants with more than a 30% decrease in plasma NT-proBNP from baseline to day 90. By day 90, a similar percentage of participants in each group had achieved this endpoint: 37.2% in the eplerenone arm compared with 30.9%, 32.5%, 37.3%, 38.8%, and 34.2% in each of the finerenone groups, respectively.

The secondary composite clinical endpoint was death from any cause, cardiovascular (CV) hospitalizations, or emergency presentation for worsening chronic HF. All finerenone groups, except for the lowest-dose group, had fewer occurrences of the secondary endpoint compared with the eplerenone group. The greatest risk reductions were seen in the finerenone group treated with 10 mg daily at the beginning of the study (HR=0.56; nominal P=.0157).

Secondary endpoints were also lower individually in the finerenone groups compared with the eplerenone groups, including CV hospitalization (HR=0.56; P=.0229), all-cause death (P=.0262), and CV death (P=.0108). Patient-reported quality of life was also consistently better with finerenone at the starting doses of 7.5 mg and 10 mg daily compared with the eplerenone group.

Adverse events were similar between the eplerenone and finerenone groups, including those leading to study drug discontinuation. Potassium elevations of 5.6 mmol/L or more occurred at equal rates in both groups (4.3%).

 “We were somewhat surprised by this striking reduction in CV events, especially mortality in the finerenone 10–20 mg group, which appears to be the optimal dose,” Dr. Filippatos said.  “Preclinical studies have shown that finerenone provides greater cardiac protection and has different binding to the receptor than eplerenone and this could be the mechanism for more pronounced organ protection that could explain better outcome. If confirmed in further, adequately powered, large-scale prospective, randomized studies, this could have important public health and health cost implications.”

Disclosures: Dr. Filippatos has served as a speaker and advisor to Bayer HealthCare AG. The study was sponsored by Bayer Healthcare AG.

Reference

1. Filippatos G, Anker SD, Böhm M, et al. FP Number 3150: Finerenone versus eplerenone in patients with worsening chronic heart failure with type 2 diabetes mellitus and/or chronic kidney disease: main results of the ARTS-HF trial. Presented at: ESC 2015; Aug. 29–Sept. 2, 2015; London.