[Significance of aldosterone antagonist therapy].
Since the introduction of ACE-inhibitors into clinical practice, the diuretic treatment with the classical aldosterone antagonist spironolactone has disappeared. It was generally believed that chronic treatment with ACE-inhibitors significantly reduces aldosterone secretion via reduction of angiotensin II-dependent aldosterone formation. However, aldosterone "escape" occurs: Even during chronic treatment with ACE-inhibitors, plasma levels of aldosterone rise again, which is associated with increased cardiovascular risk. Furthermore, extrarenal actions of aldosterone have been demonstrated, which detrimentally affect coagulation, autonomic activity, inflammatory signalling, hemodynamics, and fibrosis, subsequently leading to cardiovascular damage. Recently published studies (RALES, EPHESUS) convincingly support the concept of detrimental cardiovascular aldosterone actions even during chronic ACE-inhibition. In addition to those cardiovascular effects, aldosterone antagonism has beneficial impacts on ascites, chronic renal disease, renal volume regulation, and hypokalemia induced by diuretics. Of note, aldosterone dependent mechanisms are believed to be even involved in essential hypertension, and the value of aldosterone antagonism is currently tested in those patients. In conclusion, an old-fashioned, previously abandoned treatment strategy is currently celebrating its revival.
Christ
M
M
Klinik für Innere Medizin, Kardiologie, Philipps-Universität Marburg, christ_michael@yahoo.de
Grimm
W
W
Maisch
B
B
D000450:Aldosterone / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000077545:Eplerenone; D006333:Heart Failure / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D000451:Mineralocorticoid Receptor Antagonists; D009203:Myocardial Infarction / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D013148:Spironolactone / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone