Dickstein K, Chang P, Willenheimer R, Haunsø S, Remes J, Hall C, Kjekshus J
Hjertelaget Research Foundation, Stavanger, Norway.
J Am Coll Cardiol. 1995 Aug;26(2):438-45. doi: 10.1016/0735-1097(95)80020-h.
This study assessed the feasibility of an efficacy trial comparing angiotensin-converting enzyme inhibition and angiotensin II receptor antagonism in heart failure. Patients with moderate or severe heart failure whose condition had previously been stabilized by treatment with a converting enzyme inhibitor were randomly assigned to receive enalapril or losartan. The study was designed to detect any signs of clinical deterioration during double-blind treatment.
Losartan is a specific, nonpeptide angiotensin II receptor-1 antagonist with a vasodilator hemodynamic profile similar to that of converting enzyme inhibitors. Although therapy with specific receptor blockade has certain theoretic advantages over nonspecific converting enzyme inhibition, demonstration of a comparable therapeutic effect in patients with congestive heart failure will require a major effort comparing two active agents.
One hundred sixty-six patients with stable heart failure in New York Heart Association functional class III or IV and an ejection fraction < or = 35% were included in a multicenter, double-blind, parallel, enalapril-controlled trial. After a 3-week stabilization period with optimal therapy, including digitalis, diuretic drugs and a converting enzyme inhibitor, patients were randomly assigned to 8 weeks of therapy with losartan, 25 mg/day (n = 52); losartan, 50 mg/day (n = 56); or enalapril, 20 mg/day (n = 58). Patients were assessed with frequent clinical and laboratory evaluation and exercise testing.
No significant differences between groups in terms of changes in exercise capacity (6-min walk test), clinical status (dyspnea-fatigue index), neurohumoral activation (norepinephrine, N-terminal atrial natriuretic factor), laboratory evaluation or incidence of adverse experience were observed.
The results suggest that losartan and enalapril are of comparable efficacy and tolerability in the short-term treatment of moderate or severe congestive heart failure. A trial designed to compare the efficacy, tolerability and effect on mortality of long-term angiotensin II receptor blockade with converting enzyme inhibition is both feasible and ethically responsible.
本研究评估了一项疗效试验的可行性，该试验比较了血管紧张素转换酶抑制剂与血管紧张素II受体拮抗剂在心力衰竭治疗中的效果。中度或重度心力衰竭患者，其病情先前已通过使用转换酶抑制剂治疗得以稳定，被随机分配接受依那普利或氯沙坦治疗。该研究旨在检测双盲治疗期间任何临床恶化的迹象。
氯沙坦是一种特异性非肽类血管紧张素II受体-1拮抗剂，其血管舒张血流动力学特征与转换酶抑制剂相似。尽管特异性受体阻断疗法相对于非特异性转换酶抑制疗法具有某些理论优势，但要证明在充血性心力衰竭患者中具有相当的治疗效果，需要付出巨大努力来比较两种活性药物。
166例纽约心脏协会心功能III或IV级且射血分数≤35%的稳定心力衰竭患者纳入一项多中心、双盲、平行、依那普利对照试验。在经过3周的最佳治疗稳定期，包括使用洋地黄、利尿剂和转换酶抑制剂后，患者被随机分配接受8周的氯沙坦治疗，25毫克/天（n = 52）；氯沙坦，50毫克/天（n = 56）；或依那普利，20毫克/天（n = 58）。通过频繁的临床和实验室评估以及运动测试对患者进行评估。
在运动能力（6分钟步行试验）变化、临床状态（呼吸困难-疲劳指数）、神经体液激活（去甲肾上腺素、N末端心房利钠因子）、实验室评估或不良事件发生率方面，各治疗组间未观察到显著差异。
结果表明，氯沙坦和依那普利在中度或重度充血性心力衰竭的短期治疗中疗效和耐受性相当。一项旨在比较长期血管紧张素II受体阻断与转换酶抑制在疗效、耐受性及对死亡率影响的试验是可行且符合伦理责任的。
