Author(s): Rossignol P, Mnard J, Fay R, Gustafsson F, Pitt B,
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Abstract OBJECTIVES: The purpose of this study was to determine whether a diuretic effect may be detectable in patients treated with eplerenone, a mineralocorticoid receptor antagonist, as compared with placebo during the first month of EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival study) (n = 6,080) and whether this was associated with eplerenone's beneficial effects on cardiovascular outcomes. BACKGROUND: The mechanism of the survival benefit of eplerenone in patients with heart failure post-myocardial infarction remains uncertain. METHODS: A diuretic effect was indirectly estimated by changes at 1 month that was superior to the median changes in the placebo group in body weight (-0.05 kg) and in the estimated plasma volume reduction (+1.4\%). A potassium-sparing effect was defined as a serum potassium increase greater than the median change in the placebo group: +0.11 mmol/l. RESULTS: In the eplerenone group, body weight (p < 0.0001) and plasma volume (p = 0.047) decreased, whereas blood protein and serum potassium increased (both, p < 0.0001), as compared with the placebo group, suggesting a diuretic effect induced by eplerenone, associated with a potassium-sparing effect. A diuretic effect, as defined by an estimated plasma volume reduction, was independently associated with 11\% to 19\% better outcomes (lower all-cause death, cardiovascular death or cardiovascular hospitalization, all-cause death or hospitalization, hospitalization for heart failure). Potassium sparing was also independently associated with 12\% to 34\% better outcomes. There was no statistically significant interaction between the observed beneficial effects of eplerenone (9\% to 17\%) on cardiovascular outcomes and potassium-sparing or diuretic effects. CONCLUSIONS: Eplerenone's beneficial effects on long-term survival and cardiovascular outcomes are independent from early potassium-sparing or diuretic effects, suggesting that mineralocorticoid receptor antagonism provides cardiovascular protection beyond its diuretic and potassium-sparing properties. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
This article was published in J Am Coll Cardiol
and referenced in Anatomy & Physiology: Current Research