Cohn J N, Johnson G, Ziesche S, Cobb F, Francis G, Tristani F, Smith R, Dunkman W B, Loeb H, Wong M
University of Minnesota Medical School, Minneapolis 55455.
N Engl J Med. 1991 Aug 1;325(5):303-10. doi: 10.1056/NEJM199108013250502.
To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial.
Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine-isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment (P less than 0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P less than 0.05) during the first 13 weeks in the hydralazine-isosorbide dinitrate group.
The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination.
为了更明确血管扩张剂疗法在治疗慢性充血性心力衰竭中的疗效，我们在804名接受地高辛和利尿剂治疗心力衰竭的男性患者中，比较了肼屈嗪和硝酸异山梨酯与依那普利的疗效。患者被随机双盲分配，每日接受20毫克依那普利或每日接受300毫克肼屈嗪加160毫克硝酸异山梨酯治疗。后一种治疗方案与我们之前的血管扩张剂 - 心力衰竭试验有效治疗组中使用的方案相同，用于类似的患者群体。
依那普利组两年后的死亡率（18%）显著低于肼屈嗪 - 硝酸异山梨酯组（25%）（P = 0.016；死亡率降低28.0%），总体死亡率也趋于更低（P = 0.08）。依那普利组较低的死亡率归因于猝死发生率的降低，并且这种有益效果在症状较轻的患者（纽约心脏协会I级或II级）中更为显著。相比之下，仅肼屈嗪 - 硝酸异山梨酯治疗可使运动峰值时的身体耗氧量增加（P < 0.05），随机分组后两年内两种治疗方案均可使左心室射血分数增加，而在肼屈嗪 - 硝酸异山梨酯组中，在前13周增加得更多（P < 0.05）。
我们之前的血管扩张剂 - 心力衰竭试验中肼屈嗪 - 硝酸异山梨酯组两年死亡率（26%）和本试验中该组死亡率（25%），与之前试验中安慰剂组死亡率（34%）相比相似，以及本试验中依那普利进一步的生存获益（18%），均强化了血管扩张剂疗法应纳入心力衰竭标准治疗的结论。两种治疗方案（依那普利和肼屈嗪 - 硝酸异山梨酯）对死亡率和生理终点的不同影响表明，如果联合使用这两种方案，效果可能会增强。
