Table 1.

 Key differences between steroidal MRAs and nonsteroidal finerenone

	Steroidal MRAs		Nonsteroidal finerenone
Mode of MR antagonism	Spironolactone	Eplerenone	Finerenone Potent and selective59 Bulky and passive61
	Potent and unselective (first generation)	Less potent and more selective than spironolactone (second generation)
	Passive
Tissue distribution (in rodents)	Spironolactone	Eplerenone	Finerenone: balanced kidney–heart62
	Kidney > heart63	Kidney > heart64
Pharmacokinetics	Spironolactone: prodrug with multiple active metabolites with long half-lives65 Eplerenone: no active metabolites; half-life 4–6 h64		Finerenone: no active metabolites and short half-life66,67
Effect on cofactor recruitment in absence of aldosterone in vitro61,68	Spironolactone and eplerenone: partial agonistic cofactor recruitment		Finerenone: inverse agonist (inhibits cofactor binding in the absence of aldosterone)
Effect on cofactor recruitment in the presence of aldosterone in vitro	Spironolactone and eplerenone: inhibition of cofactor recruitment68		Finerenone: more potent and efficacious than eplerenone in blocking MR cofactor binding and inducing corepressor binding68
Effect on mutated (S810L) MR in vitro61	Spironolactone and eplerenone: agonists		Finerenone: antagonist
Effect on inflammation and fibrosis in mouse model of cardiac fibrosis68	Eplerenone (at equinatriuretic dose to finerenone): less significant effects on inflammation and fibrosis		Finerenone (at equinatriuretic dose to eplerenone): strong inhibition of inflammation and fibrosis
Effect on renal inflammation and fibrosis in a DOCA–salt rat model of CKD62	Eplerenone (at equinatriuretic dose to finerenone): significant BP reduction; less efficacious proteinuria and renal injury reduction		Finerenone (at equinatriuretic dose to eplerenone): significant systolic BP reduction only at highest dosage; greater protection from cardiac and renal injury and structural remodelling; stronger inhibition of renal expression of pro-inflammatory and pro-fibrotic markers

BP, blood pressure; CKD, chronic kidney disease; DOCA, deoxycorticosterone acetate; MR, mineralocorticoid receptor; MRA, mineralocorticoid receptor antagonist.