Swedberg K, Eneroth P, Kjekshus J, Snapinn S
Department of Medicine, Ostra Hospital, Gothenburg, Sweden.
Am J Cardiol. 1990 Oct 2;66(11):40D-44D; discussion 44D-45D. doi: 10.1016/0002-9149(90)90475-g.
This study enrolled 253 patients with severe heart failure (New York Heart Association functional class IV) from 35 centers in Scandinavia, randomly assigned to treatment with placebo or enalapril, in addition to their usual treatment for heart failure. After an initial titration period, the daily doses of enalapril ranged from 2.5 to 40 mg. At the end of the trial, 46% of the placebo-treated patients and 61% of the enalapril-treated patients were alive (p = 0.003); the survival figures at 8 months after completion of the trial were 32 and 48%, respectively (p = 0.001); and 21 and 30%, respectively (p = 0.006) at the 2-year follow-up. In the placebo group, there was a significant positive association between mortality and baseline levels of norepinephrine, epinephrine, angiotensin II, aldosterone and atrial natriuretic peptide; no such association was found in the enalapril-treated patients. The results suggest that the effects of enalapril on mortality are related to a counteraction of the neuroendocrine activation in general and to the renin-angiotensin system in particular.
本研究纳入了来自斯堪的纳维亚35个中心的253例重度心力衰竭患者(纽约心脏协会心功能IV级),除接受常规心力衰竭治疗外,随机分配接受安慰剂或依那普利治疗。经过初始滴定期后,依那普利的每日剂量范围为2.5至40毫克。试验结束时,接受安慰剂治疗的患者中有46%存活,接受依那普利治疗的患者中有61%存活(p = 0.003);试验完成后8个月的生存率分别为32%和48%(p = 0.001);2年随访时分别为21%和30%(p = 0.006)。在安慰剂组中,死亡率与去甲肾上腺素、肾上腺素、血管紧张素II、醛固酮和心房利钠肽的基线水平之间存在显著正相关;在接受依那普利治疗的患者中未发现此类相关性。结果表明,依那普利对死亡率的影响总体上与神经内分泌激活的拮抗作用有关,尤其是与肾素-血管紧张素系统有关。