Department of Cardiology and Pneumology, Heart Center, University of Göttingen, Göttingen, Germany.
JAMA. 2013 Feb 27;309(8):781-91. doi: 10.1001/jama.2013.905.
Diastolic heart failure (ie, heart failure with preserved ejection fraction) is a common condition without established therapy, and aldosterone stimulation may contribute to its progression.
To assess the efficacy and safety of long-term aldosterone receptor blockade in heart failure with preserved ejection fraction. The primary objective was to determine whether spironolactone is superior to placebo in improving diastolic function and maximal exercise capacity in patients with heart failure with preserved ejection fraction.
The Aldo-DHF trial, a multicenter, prospective, randomized, double-blind, placebo-controlled trial conducted between March 2007 and April 2012 at 10 sites in Germany and Austria that included 422 ambulatory patients (mean age, 67 [SD, 8] years; 52% female) with chronic New York Heart Association class II or III heart failure, preserved left ventricular ejection fraction of 50% or greater, and evidence of diastolic dysfunction.
Patients were randomly assigned to receive 25 mg of spironolactone once daily (n=213) or matching placebo (n=209) with 12 months of follow-up.
The equally ranked co-primary end points were changes in diastolic function (E/e') on echocardiography and maximal exercise capacity (peak VO2) on cardiopulmonary exercise testing, both measured at 12 months.
Diastolic function (E/e') decreased from 12.7 (SD, 3.6) to 12.1 (SD, 3.7) with spironolactone and increased from 12.8 (SD, 4.4) to 13.6 (SD, 4.3) with placebo (adjusted mean difference, -1.5; 95% CI, -2.0 to -0.9; P < .001). Peak VO2 did not significantly change with spironolactone vs placebo (from 16.3 [SD, 3.6] mL/min/kg to 16.8 [SD, 4.6] mL/min/kg and from 16.4 [SD, 3.5] mL/min/kg to 16.9 [SD, 4.4] mL/min/kg, respectively; adjusted mean difference, +0.1 mL/min/kg; 95% CI, -0.6 to +0.8 mL/min/kg; P = .81). Spironolactone induced reverse remodeling (left ventricular mass index declined; difference, -6 g/m2; 95% CI, -10 to-1 g/m2; P = .009) and improved neuroendocrine activation (N-terminal pro-brain-type natriuretic peptide geometric mean ratio, 0.86; 95% CI, 0.75-0.99; P = .03) but did not improve heart failure symptoms or quality of life and slightly reduced 6-minute walking distance (-15 m; 95% CI, -27 to -2 m; P = .03). Spironolactone also modestly increased serum potassium levels (+0.2 mmol/L; 95% CI, +0.1 to +0.3; P < .001) and decreased estimated glomerular filtration rate (-5 mL/min/1.73 m2; 95% CI, -8 to -3 mL/min/1.73 m2; P < .001) without affecting hospitalizations.
In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients with heart failure with preserved ejection fraction. Whether the improved left ventricular function observed in the Aldo-DHF trial is of clinical significance requires further investigation in larger populations.
clinicaltrials.gov Identifier: ISRCTN94726526; Eudra-CT No: 2006-002605-31.
舒张性心力衰竭（即射血分数保留的心力衰竭）是一种常见的疾病，没有确立的治疗方法，而醛固酮刺激可能会促进其进展。
评估长期醛固酮受体阻断在射血分数保留的心力衰竭中的疗效和安全性。主要目的是确定螺内酯是否优于安慰剂改善射血分数保留的心力衰竭患者的舒张功能和最大运动能力。
Aldo-DHF 试验是一项多中心、前瞻性、随机、双盲、安慰剂对照试验，于 2007 年 3 月至 2012 年 4 月在德国和奥地利的 10 个地点进行，包括 422 名门诊患者（平均年龄 67 [标准差 8] 岁；52%为女性），患有慢性纽约心脏协会心功能 II 或 III 级、左心室射血分数保留 50%或以上、并存在舒张功能障碍的患者。
患者随机分为接受 25 毫克螺内酯每日一次（n=213）或匹配安慰剂（n=209）治疗，随访 12 个月。
超声心动图测量的舒张功能（E/e'）和心肺运动试验测量的最大运动能力（峰值 VO2）的同等排名共同主要终点，均在 12 个月时测量。
螺内酯治疗后舒张功能（E/e'）从 12.7（标准差 3.6）降至 12.1（标准差 3.7），安慰剂治疗后从 12.8（标准差 4.4）增至 13.6（标准差 4.3）（调整后平均差异，-1.5；95%置信区间，-2.0 至 -0.9；P<0.001）。螺内酯与安慰剂相比，峰值 VO2 无显著变化（从 16.3（标准差 3.6）mL/min/kg 增加到 16.8（标准差 4.6）mL/min/kg 和从 16.4（标准差 3.5）mL/min/kg 增加到 16.9（标准差 4.4）mL/min/kg，分别；调整后平均差异，+0.1 mL/min/kg；95%置信区间，-0.6 至 +0.8 mL/min/kg；P=0.81）。螺内酯诱导逆转重构（左心室质量指数下降；差异，-6 g/m2；95%置信区间，-10 至-1 g/m2；P=0.009）并改善神经内分泌激活（N 端脑利钠肽前体比值，0.86；95%置信区间，0.75-0.99；P=0.03），但未改善心力衰竭症状或生活质量，仅略微增加 6 分钟步行距离（+15 m；95%置信区间，-27 至 -2 m；P=0.03）。螺内酯还适度增加血清钾水平（+0.2 mmol/L；95%置信区间，+0.1 至 +0.3；P<0.001）并降低估计肾小球滤过率（-5 mL/min/1.73 m2；95%置信区间，-8 至 -3 mL/min/1.73 m2；P<0.001），而不影响住院率。
在这项随机对照试验中，长期醛固酮受体阻断改善了射血分数保留的心力衰竭患者的左心室舒张功能，但对最大运动能力、患者症状或生活质量没有影响。在 Aldo-DHF 试验中观察到的左心室功能改善是否具有临床意义，需要在更大的人群中进一步研究。
clinicaltrials.gov 标识符：ISRCTN84836653；Eudra-CT 编号：2006-002605-31。
