Johnson G, Carson P, Francis G S, Cohn J N
Cooperative Studies Program Coordinating Center, VA Medical Center, West Haven, Conn.
Circulation. 1993 Jun;87(6 Suppl):VI32-9.
The effects of hydralazine plus isosorbide dinitrate were compared with those of enalapril in 804 men receiving digoxin and diuretic therapy for chronic congestive heart failure (CHF) in the Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trial (V-HeFT II).
Patients were randomly assigned to receive 20 mg of enalapril or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. At 2 years, treatment with enalapril resulted in a significant (28%) reduction in mortality relative to the active control treatment. Baseline variables were examined to determine their impact on risk of mortality and on relative response to treatment. Mortality rates were significantly higher in patients with severe ventricular arrhythmias; in patients with low baseline ejection fractions, low peak oxygen consumption, and low systolic blood pressures; in patients with high cardiothoracic ratios, high scores indicating greater impairment on a quality-of-life questionnaire, and high plasma norepinephrine or renin levels; and in patients in New York Heart Association (NYHA) classes III and IV. Coronary artery disease, duration of CHF, and patient age were not predictive of mortality. Enalapril reduced mortality significantly compared with hydralazine/isosorbide dinitrate in patient subgroups with high plasma renin or norepinephrine levels and in patients with low cardiothoracic ratios. Furthermore, enalapril conferred significantly greater protection from mortality than hydralazine/isosorbide dinitrate in patients in NYHA classes I and II and in patients without arrhythmias or with < or = 10 premature ventricular contractions per hour.
Of the prerandomization characteristics that were predictive of mortality in patients with CHF, only neurohormone measurements, cardiothoracic ratios, arrhythmia severity, and NYHA class identified subgroups of patients who benefited most from treatment with enalapril; a treatment interaction across strata was detected only for plasma norepinephrine and NYHA class. In no patient subgroup was the mortality with enalapril treatment significantly higher than the mortality with hydralazine/isosorbide dinitrate treatment.
在退伍军人事务部合作血管扩张剂 - 心力衰竭试验（V - HeFT II）中，对804名接受地高辛和利尿剂治疗慢性充血性心力衰竭（CHF）的男性患者，比较了肼屈嗪加硝酸异山梨酯与依那普利的疗效。
患者被随机分配，每日接受20 mg依那普利或300 mg肼屈嗪加160 mg硝酸异山梨酯治疗。2年后，与活性对照治疗相比，依那普利治疗使死亡率显著降低（28%）。检查基线变量以确定其对死亡风险和治疗相对反应的影响。严重室性心律失常患者、基线射血分数低、峰值耗氧量低和收缩压低的患者、心胸比高、生活质量问卷得分高表明功能损害更严重、血浆去甲肾上腺素或肾素水平高的患者以及纽约心脏协会（NYHA）III级和IV级患者的死亡率显著更高。冠状动脉疾病、CHF病程和患者年龄不能预测死亡率。在血浆肾素或去甲肾上腺素水平高以及心胸比低的患者亚组中，依那普利与肼屈嗪/硝酸异山梨酯相比显著降低死亡率。此外，在NYHA I级和II级患者以及无心律失常或每小时室性早搏≤10次的患者中，依那普利对死亡率的保护作用显著大于肼屈嗪/硝酸异山梨酯。
在CHF患者中，预测死亡率的随机前特征中，只有神经激素测量、心胸比、心律失常严重程度和NYHA分级确定了从依那普利治疗中获益最大的患者亚组；仅在血浆去甲肾上腺素和NYHA分级方面检测到跨层的治疗相互作用。在任何患者亚组中，依那普利治疗的死亡率均未显著高于肼屈嗪/硝酸异山梨酯治疗的死亡率。
