Steroidal and Novel Non-steroidal Mineralocorticoid Receptor Antagonists in Heart Failure and Cardiorenal Diseases: Comparison at Bench and Bedside
Autor: | So Young Kim, Christina Nowack, Peter Kolkhof, Bertram Pitt, Gerasimos Filippatos, Frederic Jaisser |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Finerenone Hyperkalemia business.industry 030204 cardiovascular system & hematology Pharmacology medicine.disease Eplerenone 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Mineralocorticoid receptor chemistry Heart failure Internal medicine Diabetes mellitus medicine Cardiology Spironolactone medicine.symptom business Kidney disease medicine.drug |
Zdroj: | Heart Failure ISBN: 9783319596587 |
Popis: | 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. |
Databáze: | OpenAIRE |
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