gms | German Medical Science

The steroidal mineralocorticoid-receptor antagonists (MRAs) spironolactone and eplerenone reduce mortality in patients with heart failureand a reduced ejection fraction (HFrEF). However, steroidal MRAs significantly increase the risk of hyperkalaemia and worsening renal function. Thus, they are still underused and often discontinued once administered.

Finerenone (BAY 94-8862) is a next-generation, oral, selective, non-steroidal MRA. Finerenone combines spironolactone’s potency with eplerenone’s selectivity and, based on its nonsteroidal chemical structure, it may have a more balanced cardiac versus renal activity ratio due to a combination of physicochemical properties that influence plasma transport and tissue penetration and differential affinity of the mineralocorticoid-receptor (MR)–drug complex for tissue-specific co-factors.

We investigated the tissue distribution and chronic cardiorenal end organ protection of finerenone in comparison to the steroidal MRA eplerenone in different preclinical rat disease models. Quantitative whole-body autoradiography revealed that [14C]finerenone equally distributes into rat cardiac and renal tissues. Finerenone treatment prevented deoxycorticosterone acetate/salt challenged rats from functional as well as structural heart and kidney damage at dosages not reducing systemic blood pressure. Finerenone reduced cardiac hypertrophy, plasma prohormone of brain natriuretic peptide and proteinuria more efficiently than eplerenone when comparing equi-natriuretic doses.

Finerenone has been previously studied in individuals with stable HFrEF and mild-to-moderatechronic kidney disease (CKD). In the minerAlocorticoid Receptor Antagonist Tolerability Study (ARTS; NCT01345656), finerenone 5.0–10.0 mg/day reduced plasma natriuretic peptides levels and albuminuria to the same magnitude as spironolactone 25–50 mg/day but was associated with a significantly smaller mean increase in serum potassium concentration and smaller decreases in eGFR.

Finerenone is currently investigated in four phase 2b trials, two global and two Japanese trials: ARTS-DN and ARTS-DN Japan investigate safety and efficacy of different oral doses of finerenone compared to placebo in patients with the clinical diagnosis of diabetic kidney disease. ARTS-HF and ARTS-HF Japan investigate efficacy and safety of different oral doses of finerenone compared to eplerenone in patients with worsening chronic HFrEF and concomitant type 2 diabetes mellitus and/or CKD.