TY - JOUR
T1 - Cardiovascular and Renal Outcomes with Finerenone, a Selective Mineralocorticoid Receptor Antagonist
AU - Palanisamy, Srikanth
AU - Funes Hernandez, Mario
AU - Chang, Tara I.
AU - Mahaffey, Kenneth W.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/9
Y1 - 2022/9
N2 - Overactivation of the renin–angiotensin–aldosterone system (RAAS) has been shown to be pathologic in heart failure and albuminuric chronic kidney disease (CKD), triggering pro-inflammatory and pro-fibrotic cellular pathways. The standard of care in these disease states includes treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers. Mineralocorticoid receptor antagonists (MRAs) are also a mainstay in the treatment of heart failure with reduced ejection fraction; however, therapy is often limited by treatment-related hyperkalemia. In albuminuric CKD, the risk of hyperkalemia, acute kidney injury (AKI), and hypotension also remains significant. Finerenone is a novel non-steroidal MRA that may obviate some of these concerns and have therapeutic potential in additional patient populations. Finerenone was developed using the chemical structure of a dihydropyridine channel blocker but optimized to create a bulky MRA without any activity at the L-type calcium channel. It has several novel cellular mechanisms that may account for its ability to reduce cardiac hypertrophy and proteinuria more efficiently than an equinatriuretic dose of a steroidal MRA, while retaining anti-inflammatory and anti-fibrotic properties. Finerenone also has a lower rate of treatment-related hyperkalemia and AKI than steroidal MRAs with a smaller effect on systolic blood pressure, greatly expanding its therapeutic utility. The recently published FIGARO-DKD and FIDELIO-DKD trials demonstrate that treatment with finerenone in patients with type II diabetes and albuminuric CKD results in improved cardiovascular outcomes and a lower risk of CKD progression. Patients enrolled in these studies were already on maximally tolerated ACE inhibitor or angiotensin receptor blocker therapy. Trials investigating finerenone’s therapeutic effect in patients with heart failure with preserved ejection fraction (HFpEF) and non-diabetic CKD, as well sodium–glucose cotransporter 2 (SGLT2) and finerenone combination therapy in patients with diabetic nephropathy, are ongoing.
AB - Overactivation of the renin–angiotensin–aldosterone system (RAAS) has been shown to be pathologic in heart failure and albuminuric chronic kidney disease (CKD), triggering pro-inflammatory and pro-fibrotic cellular pathways. The standard of care in these disease states includes treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers. Mineralocorticoid receptor antagonists (MRAs) are also a mainstay in the treatment of heart failure with reduced ejection fraction; however, therapy is often limited by treatment-related hyperkalemia. In albuminuric CKD, the risk of hyperkalemia, acute kidney injury (AKI), and hypotension also remains significant. Finerenone is a novel non-steroidal MRA that may obviate some of these concerns and have therapeutic potential in additional patient populations. Finerenone was developed using the chemical structure of a dihydropyridine channel blocker but optimized to create a bulky MRA without any activity at the L-type calcium channel. It has several novel cellular mechanisms that may account for its ability to reduce cardiac hypertrophy and proteinuria more efficiently than an equinatriuretic dose of a steroidal MRA, while retaining anti-inflammatory and anti-fibrotic properties. Finerenone also has a lower rate of treatment-related hyperkalemia and AKI than steroidal MRAs with a smaller effect on systolic blood pressure, greatly expanding its therapeutic utility. The recently published FIGARO-DKD and FIDELIO-DKD trials demonstrate that treatment with finerenone in patients with type II diabetes and albuminuric CKD results in improved cardiovascular outcomes and a lower risk of CKD progression. Patients enrolled in these studies were already on maximally tolerated ACE inhibitor or angiotensin receptor blocker therapy. Trials investigating finerenone’s therapeutic effect in patients with heart failure with preserved ejection fraction (HFpEF) and non-diabetic CKD, as well sodium–glucose cotransporter 2 (SGLT2) and finerenone combination therapy in patients with diabetic nephropathy, are ongoing.
KW - Chronic kidney disease
KW - Diabetic nephropathy
KW - Finerenone
KW - Heart failure
KW - MRA
UR - http://www.scopus.com/inward/record.url?scp=85132579986&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85132579986&partnerID=8YFLogxK
U2 - 10.1007/s40119-022-00269-3
DO - 10.1007/s40119-022-00269-3
M3 - Review article
AN - SCOPUS:85132579986
SN - 2193-8261
VL - 11
SP - 337
EP - 354
JO - Cardiology and Therapy
JF - Cardiology and Therapy
IS - 3
ER -