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A randomized trial of the aldosterone-receptor antagonist eplerenone in asymptomatic moderate-severe aortic stenosis.

Author(s): Stewart RA, Kerr AJ, Cowan BR, Young AA, Occleshaw C, Richards AM, Edwards C, Whalley GA, Freidlander D, Williams M, Doughty RN, Zeng I, White HD, ZEST Study Investigators

Affiliation(s): Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand. rstewart@adhb.govt.nz

Publication date & source: 2008-08, Am Heart J., 156(2):348-55. Epub 2008 Jun 4.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

BACKGROUND: The aim of the study is to determine whether the selective aldosterone-receptor antagonist eplerenone delays onset of left ventricular (LV) systolic dysfunction or reduces LV hypertrophy in asymptomatic patients with moderate to severe aortic stenosis. Effects of eplerenone on LV diastolic function and progression of valve stenosis were also evaluated. METHODS: Sixty-five asymptomatic patients with a peak aortic valve velocity >3.0 m/s and normal LV function were randomized double blind to eplerenone, 100 mg daily (n = 33), or placebo (n = 32) for a median of 19 (interquartile range 15 to 25) months. Cardiac magnetic resonance imaging and echocardiography were performed and N-terminal pro-brain natriuretic peptide was measured at baseline and follow-up. RESULTS: Symptomatic deterioration occurred in 13 subjects randomized to eplerenone and 11 to placebo (P = .34). Change in LV mass index (mean change +/- SD -0.3 +/- 14.6 vs +5.1 +/- 15 g/m(2) per year, P = .3), LV ejection fraction (+0.0% +/- 5.7% vs +0.8% +/- 5.7% per year, P = .9), and LV end-systolic volume index (-1.2 +/- 9 vs +0.04 +/- 12 mL/m(2) per year, P = .8) were small and similar for patients randomized to eplerenone and placebo, respectively. Decrease of aortic valve area (-0.11 +/- 0.22 vs -0.18 +/- 0.24 cm(2)/y, P = .2), worsening of LV diastolic dysfunction by echo-Doppler (E/E' +0.49 +/- 0.7 vs +1.32 +/- 2.0/year, P = .4), increase in the plasma level of N-terminal pro-brain natriuretic peptide (+63% vs +12% per year, P = .1), and decline in physical function score (9 +/- 34 vs 12 +/- 37/year, P = .7) were similar for subjects randomized to eplerenone and placebo, respectively. CONCLUSIONS: In asymptomatic patients with moderate-severe aortic stenosis, eplerenone did not slow onset of LV systolic or diastolic dysfunction, decrease LV mass, or reduce progression of valve stenosis.

Page last updated: 2008-08-10

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