Cohn J N, Archibald D G, Ziesche S, Franciosa J A, Harston W E, Tristani F E, Dunkman W B, Jacobs W, Francis G S, Flohr K H
N Engl J Med. 1986 Jun 12;314(24):1547-52. doi: 10.1056/NEJM198606123142404.
To evaluate the effects of vasodilator therapy on mortality among patients with chronic congestive heart failure, we randomly assigned 642 men with impaired cardiac function and reduced exercise tolerance who were taking digoxin and a diuretic to receive additional double-blind treatment with placebo, prazosin (20 mg per day), or the combination of hydralazine (300 mg per day) and isosorbide dinitrate (160 mg per day). Follow-up averaged 2.3 years (range, 6 months to 5.7 years). Mortality over the entire follow-up period was lower in the group that received hydralazine and isosorbide dinitrate than in the placebo group. This difference was of borderline statistical significance. For mortality by two years, a major end point specified in the protocol, the risk reduction among patients treated with both hydralazine and isosorbide dinitrate was 34 percent (P less than 0.028). The cumulative mortality rates at two years were 25.6 percent in the hydralazine--isosorbide dinitrate group and 34.3 percent in the placebo group; at three years, the mortality rate was 36.2 percent versus 46.9 percent. The mortality-risk reduction in the group treated with hydralazine and isosorbide dinitrate was 36 percent by three years. The mortality in the prazosin group was similar to that in the placebo group. Left ventricular ejection fraction (measured sequentially) rose significantly at eight weeks and at one year in the group treated with hydralazine and isosorbide dinitrate but not in the placebo or prazosin groups. Our data suggest that the addition of hydralazine and isosorbide dinitrate to the therapeutic regimen of digoxin and diuretics in patients with chronic congestive heart failure can have a favorable effect on left ventricular function and mortality.
为评估血管扩张剂治疗对慢性充血性心力衰竭患者死亡率的影响，我们将642名心功能受损且运动耐量降低、正在服用地高辛和利尿剂的男性患者随机分组，使其接受额外的双盲治疗，分别给予安慰剂、哌唑嗪（每日20毫克）或肼屈嗪（每日300毫克）与硝酸异山梨酯（每日160毫克）的联合用药。随访平均时间为2.3年（范围为6个月至5.7年）。在整个随访期内，接受肼屈嗪和硝酸异山梨酯联合用药的组的死亡率低于安慰剂组。这种差异具有边缘统计学意义。对于方案中规定的主要终点——两年时的死亡率，接受肼屈嗪和硝酸异山梨酯联合治疗的患者的风险降低了34%（P小于0.028）。肼屈嗪-硝酸异山梨酯组两年时的累积死亡率为25.6%，安慰剂组为34.3%；三年时，死亡率分别为36.2%和46.9%。到三年时，接受肼屈嗪和硝酸异山梨酯联合治疗的组的死亡风险降低了36%。哌唑嗪组的死亡率与安慰剂组相似。在接受肼屈嗪和硝酸异山梨酯联合治疗的组中，左心室射血分数（连续测量）在8周和1年时显著升高，而在安慰剂组或哌唑嗪组中则未升高。我们的数据表明，在慢性充血性心力衰竭患者的地高辛和利尿剂治疗方案中添加肼屈嗪和硝酸异山梨酯，可能对左心室功能和死亡率产生有益影响。
