Stewart Ralph A H, Kerr Andrew J, Cowan Brett R, Young Alistair A, Occleshaw Christopher, Richards A Mark, Edwards Colin, Whalley Gillian A, Freidlander Denis, Williams Miles, Doughty Robert N, Zeng Irene, White Harvey D
Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
Am Heart J. 2008 Aug;156(2):348-55. doi: 10.1016/j.ahj.2008.03.012. Epub 2008 Jun 4.
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.
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.
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.
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.
本研究旨在确定选择性醛固酮受体拮抗剂依普利酮是否能延缓中度至重度主动脉瓣狭窄无症状患者左心室（LV）收缩功能障碍的发生或减轻左心室肥厚。还评估了依普利酮对左心室舒张功能和瓣膜狭窄进展的影响。
65例主动脉瓣峰值流速>3.0 m/s且左心室功能正常的无症状患者被随机双盲分为依普利酮组（每日100 mg，n = 33）或安慰剂组（n = 32），中位治疗时间为19个月（四分位间距15至25个月）。在基线和随访时进行心脏磁共振成像和超声心动图检查，并测量N末端脑钠肽前体。
随机分组至依普利酮组的13名受试者和安慰剂组的11名受试者出现症状恶化（P = 0.34）。随机分组至依普利酮组和安慰剂组的患者，左心室质量指数变化（平均变化±标准差，每年-0.3±14.6 vs +5.1±15 g/m²，P = 0.3）、左心室射血分数（每年+0.0%±5.7% vs +0.8%±5.7%，P = 0.9）和左心室收缩末期容积指数（每年-1.2±9 vs +0.04±12 mL/m²，P = 0.8）均较小且相似。主动脉瓣面积减小（-0.11±0.22 vs -0.18±0.24 cm²/年，P = 0.2）、经超声多普勒检查左心室舒张功能障碍恶化（E/E'+0.49±0.7 vs +1.32±2.0/年，P = 0.4）、N末端脑钠肽前体血浆水平升高（每年+63% vs +12%，P = 可编辑）和身体功能评分下降（每年9±34 vs 12±37，P = 0.7）在随机分组至依普利酮组和安慰剂组的受试者中也相似。
在中度至重度主动脉瓣狭窄无症状患者中，依普利酮并未延缓左心室收缩或舒张功能障碍的发生、减轻左心室质量或减缓瓣膜狭窄进展。
