Pacher R, Stanek B, Globits S, Berger R, Hülsmann M, Wutte M, Frey B, Schuller M, Hartter E, Ogris E
Department of Cardiology, University of Vienna, Austria.
Eur Heart J. 1996 Aug;17(8):1223-32. doi: 10.1093/oxfordjournals.eurheartj.a015040.
Angiotensin converting enzyme inhibitors improve symptoms and prolong life in congestive heart failure, but the dose in the individual patient is uncertain. A randomized, 48-week, double-blind study was performed to investigate the safety and efficacy of 'high' in comparison to continued 'low' angiotensin converting enzyme inhibitor therapy in severe heart failure. Eighty-three patients (56 +/- 1.1 years; 69 men, 14 women) in New York Heart Association functional class III/IV on digoxin, furosemide and 'low' angiotensin converting enzyme inhibitors (captopril < or = 50 mg.day-1 or enalapril < or = 10 mg.day-1) were included. After a > or = 14 day run-in on 10 mg.day-1 enalapril, digitalis and furosemide, right heart catheterization at rest and exercise was performed. All patients presented with atrial pressure > 10 mmHg and/or pulmonary artery pressure > 35 mmHg, and/or cardiac index < 2.5 l.min-1.m-2 at rest. Patients then received enalapril 5 mg twice daily (n = 42), or 20 mg twice daily (n = 41) in random order. Thus, patients randomized to low doses of enalapril actually had no change in therapy from baseline to 48 weeks. Forty-three patients (52%) completed the study, 19 patients on the low dose and 24 patients on the high dose. Both dosages equally influenced survival with 15 (18%) deaths, eight on low dose and seven on high dose. After 48 weeks, functional capacity by New York Heart Association class improved more on the high dose than on the low dose (P = 0.04). In contrast, alterations in invasive haemodynamic variables at rest and exercise as well as maximal exercise capacity were comparable in both groups. Diastolic blood pressure decreased and the change between both groups was statistically significant (P = 0.01). Changes in plasma creatinine levels did not differ between high and low dose treatment and no patients had to be withdrawn because of deterioration in kidney function. With regard to neurohumoral activity, a tendency to a discrepant response to both treatments was observed with a blunted increase in noradrenaline on high versus low enalapril dose. Thus, high-dose enalapril treatment proved superior to low dose as regards symptomatology in severe heart failure after long-term treatment, despite similar effects on haemodynamics and on maximal exercise capacity.
血管紧张素转换酶抑制剂可改善充血性心力衰竭患者的症状并延长其寿命，但个体患者的用药剂量尚不确定。一项随机、为期48周的双盲研究开展，旨在调查在重度心力衰竭中，与持续“低剂量”血管紧张素转换酶抑制剂治疗相比，“高剂量”治疗的安全性和有效性。纳入了83例纽约心脏病协会心功能分级为III/IV级、正在服用地高辛、呋塞米和“低剂量”血管紧张素转换酶抑制剂（卡托普利≤50mg/天或依那普利≤10mg/天）的患者（年龄56±1.1岁；男性69例，女性14例）。在以10mg/天依那普利、洋地黄和呋塞米进行≥14天的导入期后，进行静息和运动状态下的右心导管检查。所有患者静息时均存在心房压>10mmHg和/或肺动脉压>35mmHg，和/或心脏指数<2.5l·min-1·m-2。然后患者随机接受依那普利5mg每日两次（n = 42）或20mg每日两次（n = 41）治疗。因此，随机分配至低剂量依那普利组的患者从基线到48周治疗实际上没有变化。43例患者（52%）完成了研究，19例接受低剂量治疗，24例接受高剂量治疗。两种剂量对生存率的影响相同，有15例（18%）死亡，低剂量组8例，高剂量组7例。48周后，纽约心脏病协会分级的功能能力在高剂量组比低剂量组改善更明显（P = 0.04）。相比之下，两组静息和运动时的有创血流动力学变量变化以及最大运动能力相当。舒张压降低，两组间变化具有统计学意义（P = 0.01）。高剂量和低剂量治疗组血浆肌酐水平变化无差异，且没有患者因肾功能恶化而退出研究。关于神经体液活性，观察到两种治疗的反应存在差异的趋势，高剂量依那普利组去甲肾上腺素升高减弱。因此，尽管高剂量依那普利和低剂量依那普利对血流动力学和最大运动能力的影响相似，但在长期治疗后，高剂量依那普利治疗在重度心力衰竭症状方面优于低剂量治疗。
