Finerenone vs. Eplerenone: Trial Shows Mixed Results

In heart failure patients with diabetes and/or chronic kidney disease, a new, non-steroidal mineralocorticoid receptor antagonist (MRA) called finerenone was no more effective than the currently approved MRA eplerenone in reducing the heart failure biomarker N-terminal pro-B-type natriuretic peptide [NT-proBNP].

But results of the ARTS-HF trial, presented in London, UK, at the European Society of Cardiology Congress 2015, suggest that “finerenone may offer more pronounced end-organ protection than eplerenone,” said Gerasimos Filippatos, MD, of Athens University Hospital Attikon in Athens, Greece.

“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 heart failure,” said Professor Filippatos, from Athens University Hospital Attikon in Athens, Greece.

Patients were randomized into six groups, one group receiving eplerenone, and the other five groups receiving different doses of finerenone for 90 days.

The primary endpoint was the percentage of individuals with more than a 30% decrease in plasma NT-proBNP from baseline to day 90, with a composite clinical secondary endpoint of death from any cause, cardiovascular (CV) hospitalizations, or emergency presentation for worsening chronic heart failure. Changes in health related quality of life (QOL) were also measured.

Dosing of all medications was up-titrated through the study period. The eplerenone group started with a dose of 25 mg every other day, increasing to 25 mg daily on Day 30, with up-titration to 50 mg daily by Day 60.

The finerenone groups started with 2.5 mg, 5 mg, 7.5 mg, 10 mg or 15 mg daily, 5mg, 10mg, 15mg, 20mg and 20 mg respectively on Day 30, provided that blood potassium remained at or below 5.0 mmol/L.

By Day 90, a similar percentage of patients in each group had achieved the primary endpoint of more than a 30% decrease in plasma NT-proBNP (37.2% in the eplerenone arm compared to and 30.9%, 32.5%, 37.3%, 38.8% and 34.2% in each of the finerenone dose groups).

The secondary composite clinical endpoint occurred less frequently in all patients treated with finerenone (except for the lowest dose ) compared with the eplerenone-treated patients, with the greatest risk reduction in the finerenone-treated patients who started at 10 mg daily (HR 0.56; nominal P= 0.0157).

Eplerenone, as well as spironolactone distribute several fold greater to the kidneys than the heart - whereas finerenone is equally distributed to the kidney and heart —thereby providing relatively greater cardiac vs renal protection. The researchers said, adding “The greater reduction in cardiovascular events with finerenone in our study we believe can in part be attributed to this more favorable distribution of finerenone as well as differences in its mode of binding to the MR compared to eplerenone.

The study was funded by Bayer HealthCare.