Aldosterone inhibition and cardiovascular protection: more important than it once appeared.
Aldosterone is present and active all along the cardiovascular continuum. Excessive tissue production occurs in cardiovascular diseases including myocardial infarction (MI) and heart failure, resulting in a multitude of adverse effects in the cardiovascular system necessitating pharmacologic blockade of this neurohormone. Both human and animal studies have consistently proven the beneficial effects of antialdosteronics in the improvement of: 1) endothelial function, 2) modulation of inflammatory mechanisms between blood and the vascular wall and 3) reduction of tissue proliferation and cardiovascular remodeling leading to different severities of cardiovascular damage. These basic mechanisms of anti-aldosterone therapy strongly support the promising data observed in major clinical trials with aldosterone blockers in cardiovascular diseases, specially in heart failure patients. Whereas aldosterone receptor blockers were initially viewed as potassium-sparing diuretics there has been a clear change of concept in the past 10 years, mainly following the positive results of RALES with spironolactone in chronic heart failure, followed by EPHESUS using eplerenone in patients with systolic dysfunction post MI. The significant positive results in both studies were a clear support for the inclusion of this pharmacologic intervention as first line treatment in most international guidelines for the management of heart failure. More recent and ongoing studies are exploring the usefulness of this type of intervention in preventing vascular and myocardial hypertrophy and remodeling in refractory hypertensive and some hyperfibrotic syndromes. There are also provocative studies investigating in the possibility of inhibiting atherosclerosis. More recently, some studies are suggesting the benefit of aldosterone blockade in sleep apnea. In addition, two large multicentric trials, TOPCAT and EMPHASIS are analyzing the potential use of antialdosteronics in patients with cardiac insufficiency and preserved systolic function and the possibility of extending their indication in systolic heart failure to Phase II respectively. New compounds, blocking the synthesis of aldosterone instead of blocking its receptor are being developed, and initial Phase 2 studies are positive. All of the above results are very interesting, show an optimistic future and are consolidating and enlarging the spectrum of aldosterone blockade in cardiovascular disorders every day.
Martinez
Felipe A
FA
DAMIC- Rusculleda Foundation, National University of Córdoba, Av. Colon 2057, Córdoba, Argentina. dr.martinez@usa.net
D000450:Aldosterone / Q000502:physiology*; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006332:Cardiomegaly / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D015337:Multicenter Studies as Topic; D009203:Myocardial Infarction / Q000150:complications; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D012891:Sleep Apnea Syndromes / Q000150:complications / Q000188:drug therapy; D013148:Spironolactone / Q000494:pharmacology; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology
D002316:Cardiotonic Agents; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000450:Aldosterone