Characterization of mice with cell-specific deletion or overexpression of the
mineralocorticoid receptor (MR) shed a new light on its role in health and disease. Pathophysiological MR activation contributes to a plethora of deleterious molecular mechanisms in the development of cardiorenal diseases like
chronic kidney disease (CKD) and
heart failure (HF). Accordingly, the available steroidal MR antagonists (MRAs)
spironolactone (first generation MRA) and
eplerenone (second generation MRA) have been shown to be effective in reducing cardiovascular (CV) mortality and morbidity in patients with chronic HF and a reduced left ventricular ejection fraction (HFrEF). However, they remain underutilized, in large part owing to the risk inducing severe adverse events including
hyperkalemia and worsening of kidney function, particularly when given on top of inhibitors of the renin angiotensin system (RAS) to patients with concomitant kidney dysfunction. Novel, potent, and selective non-steroidal MRAs (third generation) were identified in drug discovery campaigns and a few entered clinical development recently. One of these is
finerenone with different physicochemical, pharmacokinetics, and pharmacological properties in comparison with the steroidal MRAs. Available data from five clinical phase II trials with
finerenone in more than 2,000 patients with HF and additional CKD and/or diabetes as well as in patients with
diabetic kidney disease demonstrated that neither
hyperkalemia nor reductions in kidney function were limiting factors to its use. Moreover,
finerenone demonstrated a nominally improved outcome compared to
eplerenone in a phase IIb trial with 1,066 patients with HFrEF and concomitant
type 2 diabetes mellitus (T2DM) and/or CKD.