PMID- 27830348
OWN - NLM
STAT- MEDLINE
DCOM- 20171024
LR  - 20210721
IS  - 0171-2004 (Print)
IS  - 0171-2004 (Linking)
VI  - 243
DP  - 2017
TI  - Steroidal and Novel Non-steroidal Mineralocorticoid Receptor Antagonists in Heart 
      Failure and Cardiorenal Diseases: Comparison at Bench and Bedside.
PG  - 271-305
LID - 10.1007/164_2016_76 [doi]
AB  - 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.
FAU - Kolkhof, Peter
AU  - Kolkhof P
AD  - Drug Discovery, Cardiology Research, Bayer Pharma AG, Building 500, Aprather Weg 
      18a, 42096, Wuppertal, Germany. peter.kolkhof@bayer.com.
FAU - Jaisser, Frederic
AU  - Jaisser F
AD  - INSERM, UMRS 1138, Team 1, Centre de Recherche des Cordeliers, Pierre et Marie 
      Curie University, Paris Descartes University, Paris, France.
FAU - Kim, So-Young
AU  - Kim SY
AD  - Clinical Development, Bayer Pharma AG, 42096, Wuppertal, Germany.
FAU - Filippatos, Gerasimos
AU  - Filippatos G
AD  - Department of Cardiology, National and Kapodistrian University of Athens, School 
      of Medicine, Attikon University Hospital, Rimini 1, Haidari, Athens, 12462, 
      Greece.
FAU - Nowack, Christina
AU  - Nowack C
AD  - Clinical Development, Bayer Pharma AG, 42096, Wuppertal, Germany.
FAU - Pitt, Bertram
AU  - Pitt B
AD  - University of Michigan Medical School, Ann Arbor, MI, USA.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Germany
TA  - Handb Exp Pharmacol
JT  - Handbook of experimental pharmacology
JID - 7902231
RN  - 0 (Mineralocorticoid Receptor Antagonists)
RN  - 0 (Naphthyridines)
RN  - 0 (Receptors, Mineralocorticoid)
RN  - 0 (finerenone)
RN  - 27O7W4T232 (Spironolactone)
RN  - 6995V82D0B (Eplerenone)
SB  - IM
MH  - Animals
MH  - Cardio-Renal Syndrome/*drug therapy
MH  - Diabetic Nephropathies/complications/*drug therapy
MH  - Endothelial Cells/drug effects/metabolism
MH  - Eplerenone
MH  - Fibroblasts/drug effects/metabolism
MH  - Heart Failure/complications/*drug therapy/physiopathology
MH  - Humans
MH  - Macrophages/drug effects/metabolism
MH  - Mineralocorticoid Receptor Antagonists/pharmacology/*therapeutic use
MH  - Muscle, Smooth, Vascular
MH  - Myocytes, Cardiac/drug effects/metabolism
MH  - Myocytes, Smooth Muscle/drug effects/metabolism
MH  - Naphthyridines/pharmacology/*therapeutic use
MH  - Receptors, Mineralocorticoid/metabolism
MH  - Spironolactone/*analogs & derivatives/pharmacology/*therapeutic use
MH  - Stroke Volume
OTO - NOTNLM
OT  - Chronic kidney disease
OT  - Eplerenone
OT  - Finerenone
OT  - Heart failure
OT  - Mineralocorticoid receptor antagonists
OT  - Spironolactone
EDAT- 2016/11/11 06:00
MHDA- 2017/10/25 06:00
CRDT- 2016/11/11 06:00
PHST- 2016/11/11 06:00 [pubmed]
PHST- 2017/10/25 06:00 [medline]
PHST- 2016/11/11 06:00 [entrez]
AID - 10.1007/164_2016_76 [doi]
PST - ppublish
SO  - Handb Exp Pharmacol. 2017;243:271-305. doi: 10.1007/164_2016_76.