Steroidal and Non-steroidal Mineralocorticoid Receptor Antagonists in Cardiorenal Medicine

Rajiv Agarwal; Peter Kolkhof; George Bakris; Johann Bauersachs; Hermann Haller; Takashi Wada; Faiez Zannad

Disclosures

Eur Heart J. 2021;42(2):152-161. 

In This Article

Conclusions

MR overactivation results in deleterious effects on the kidneys and heart, promoting inflammation and fibrosis, and progression of kidney and CV disease; effects that extend beyond the well-recognized retention of salt and water and downstream hypertension. MRKO studies demonstrated that MR antagonism could play a key role in addressing the residual risk of progression of kidney and heart disease. MRAs can be categorized as steroidal or nonsteroidal, with key differences in molecular and pharmacological properties between them. The novel, nonsteroidal, selective MRA finerenone shows several promising differences from steroidal MRAs in preclinical models, with a mechanism of action distinct from other emerging agents for cardiorenal medicine in CKD and T2D. In the Phase III randomized trial, FIDELIO-DKD, finerenone significantly reduced the primary and secondary composite endpoints vs. placebo, suggesting that finerenone may forestall progression to kidney failure in patients with CKD and T2D.[82] The FIGARO-DKD study will further address whether finerenone can reduce the risk of major adverse CV events in this patient population. Combined, these studies should firmly establish the role of finerenone in cardiorenal medicine.

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