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ESC: Novel HF Drug Could Cut Mortality

— Non-steroidal mineralcorticoid receptor antagonist promising in phase II

MedpageToday

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LONDON -- The investigational non-steroidal mineralcorticoid receptor antagonist finerenone worked as well as eplerenone (Inspra) with a possible mortality advantage over the older drug in heart failure, the phase II ARTS-HF trial suggested.

Reductions in NT-proBNP of more than 30% from baseline to day 90, the study's primary endpoint, occurred in 37.2% of eplerenone-treated patients compared with 30.9% to 38.8% of finerenone-treated patients across doses tested (P not significant), , of Athens University Hospital Attikon in Greece, and colleagues found.

A composite of all-cause mortality, cardiovascular hospitalization or emergency presentation for worsening chronic heart failure was lower at the end of the study period at day 90 with all finerenone doses, except the lowest (2.5 to 5 mg), than with eplerenone.

The lowest incidence of that secondary endpoint was seen with an intermediate dose of finerenone (10 to 20 mg), "which appears to be the optimal dose," the researchers reported here at the European Society of Cardiology meeting.

The hazard ratio with that dose versus eplerenone was 0.56 (95% confidence interval 0.34 to 0.93) for cardiovascular hospitalization and 0.14 (95% CI 0.02 to 1.07) for all-cause mortality.

The dose-ranging ARTS-HF (MinerAlocorticoid Receptor AnTagonist Study In Heart Failure) trial included 1,055 patients (mean age 71), who presented to the emergency department with worsening heart failure and type 2 diabetes, chronic kidney disease, or both.

Finerenone has greater receptor selectivity than spironolactone and better receptor affinity than eplerenone, resulting in equal distribution to the heart and kidneys compared with greater kidney than heart distribution for the other two agents, the researchers noted.

The rate of hyperkalemia of at least 5.6 mmol/L was 4.3% across finerenone dose groups compared with 4.7% with eplerenone. The proportion who reached 6.0 mmol/L was 0.5% with both drugs.

An EGFR drop of at least 40% was 9.4% with eplerenone compared with 9.1% across finerenone dose groups.

Mean change in potassium from baseline to day 90 was significantly lower with the lower finerenone doses than with eplerenone, but similar for the 10 to 20 mg dose favored by the trial.

The findings closely followed those of a second phase II trial reported this week, ARTS-DN, that showed better renal biomarker results with finerenone compared with placebo in diabetic nephropathy.

Disclosures

The study was funded by Bayer Healthcare.

Filippatos disclosed financial relationships with Bayer HealthCare.

Primary Source

European Society of Cardiology

Filippatos G, et al "Results of ARTS-HF: finerenone versus eplerenone in patients with worsening chronic heart failure and diabetes and/or chronic kidney disease" ESC 2015.