Aldosterone antagonism and congestive heart failure: a new look at an old therapy.
OBJECTIVE
More than 5 million people in the United States alone have congestive heart failure, and an estimated 40 million have established risks and warrant therapy. Mineralocorticoid antagonists have emerged as a new paradigm for the treatment of congestive heart failure. They have established benefits among patients with chronic symptomatic systolic dysfunction, and recent studies have demonstrated substantial effect on the morbidity and mortality among patients with heart failure after myocardial infarction. The exact biologic mechanism is thus far unknown.


RESULTS
Within the last 5 years, efforts have intensified to help define better the biologic mechanisms by which mineralocorticoid receptor antagonisms exert the observed clinical benefit. Elegant human studies have demonstrated some important observations. First, under conditions of increased plasma aldosterone concentrations, the heart will extract aldosterone. Second, aldosterone extraction in the heart stimulates increased collagen turnover culminating in ventricular remodeling. Third, among people with chronic systolic or diastolic heart failure, aldosterone is actually produced and secreted by the heart. Finally, antagonism of the mineralocorticoid receptor will attenuate or abrogate many of these deleterious effects.


CONCLUSIONS
Combined clinical and detailed mechanistic investigations have established mineralocorticoid receptor antagonism as the new treatment paradigm for congestive heart failure. Recent clinical data have demonstrated that treatment of patients with a combination of mineralocorticoid receptor antagonism (eplerenone) and angiotensin converting enzyme-inhibitor (ACE-I) results in substantial reduction in left ventricular mass. Furthermore, a federally funded initiative to treat more than 6000 patients with diastolic heart failure with spironolactone is in its final phases of planning. It is foreseeable that, along with ACE-I and beta-blockers, mineralocorticoid receptor antagonism will become part of the treatment paradigm for people across the entire spectrum of cardiovascular disease.
Thohan
Vinay
V
DeBakey Heart Center, Winters Center for Heart Failure Research, Houston, Texas, USA. vthohan@bcm.tmc.edu
Torre-Amione
Guillermo
G
Koerner
Micheal M
MM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use; D000077545:Eplerenone; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000150:complications; D016032:Randomized Controlled Trials as Topic; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone; D004656:Enalapril