Eplerenone: will it have a role in the treatment of acute coronary syndromes?
Aldosterone is known to have multiple adverse cardiovascular effects that are reminiscent of but independent from angiotensin II. These effects include endothelial dysfunction, heightened thrombogenicity, inflammation, and reparative fibrosis, and have been described in experimental and human models of aldosterone excess. Recently a number of clinical investigations have demonstrated that mineralocorticoid receptor (MR) antagonism, even in conditions not traditionally associated with systemic activation of the renin-angiotensin II-aldosterone pathway, may provide additional benefits above and beyond angiotensin-converting enzyme (ACE) inhibition and angiotensin receptor blockade. The Eplerenone Neurohormonal Efficacy and Survival Study (EPHESUS) with eplerenone in patients who were post-myocardial infarction underscores the additive benefit of such a strategy in post-infarction patients that typify an at-risk population for recurrent cardiovascular events. The mechanisms operative in acute coronary syndromes (ACS), including inflammation, altered hemostasis, and endothelial dysfunction, overlap significantly with those seen in the EPHESUS patient population. One may therefore hypothesize that MR antagonism with eplerenone may be beneficial in patients with ACS. Another advantage of using eplerenone is that it offers the advantages of MR antagonism without the side effects due to blockade of other nuclear receptors such as the androgen and progesterone receptors. If MR blockade is found to be beneficial in patients with ACS, the potential reduction in morbidity, mortality, and health care costs are profound.
Meier
David J
DJ
The Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6574, USA.
Pitt
Bertram
B
Rajagopalan
Sanjay
S
D000789:Angina, Unstable / Q000188:drug therapy* / Q000503:physiopathology; D015906:Angioplasty, Balloon, Coronary; D003094:Collagen / Q000378:metabolism; D023903:Coronary Restenosis / Q000378:metabolism; D000077545:Eplerenone; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D000451:Mineralocorticoid Receptor Antagonists; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D013577:Syndrome; D013927:Thrombosis / Q000503:physiopathology
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone; D003094:Collagen