MacFadyen R J, Lees K R, Reid J L
University Department of Medicine and Therapeutics, University of Glasgow.
Br Heart J. 1991 Sep;66(3):206-11. doi: 10.1136/hrt.66.3.206.
To compare the first dose responses to low dose angiotensin converting enzyme inhibitors (captopril, enalapril, and perindopril) in elderly patients with stable chronic heart failure.
Double blind, randomised, placebo controlled, parallel, group prospective study of elderly patients with stable chronic heart failure.
General hospital in-patient admissions for supervised diuretic withdrawal (24-48 hours) and the introduction of angiotensin converting enzyme inhibitor therapy.
48 unselected elderly (58-85 years) patients with symptomatic but stable chronic heart failure (New York Heart Association grades II-IV) confirmed by clinical history, examination, and cardiological investigations. Patients gave their written and informed consent to receive their initial treatment under double blind conditions; blood pressure was monitored and blood samples taken to measure the pharmacokinetic and neurohormonal responses.
Patients were randomised to receive a daily oral dose of placebo, captopril (6.25 mg), enalapril (2.5 mg), or perindopril (2 mg).
Blood pressure and heart rate responses, drug concentration, and plasma renin and ACE activities. Differences between treatment groups were analysed by analysis of variance.
The four randomised groups of patients had similar age, severity of heart failure (NYHA class), pretreatment diuretic dosage, plasma renin activity, and serum electrolyte state. Placebo treatment caused a modest but significant diurnal fall in blood pressure. Captopril produced a significant early (1.5 hours) and brief fall in blood pressure. The blood pressure fall with enalapril was later (4-10 hours), longer lasting, and was associated with significant slowing of supine heart rate. Though perindopril produced a similar plasma ACE inhibition to that produced by enalapril, it only caused changes in blood pressure that were similar to those caused by placebo.
This controlled study is the first to indicate a qualitative difference in the acute response to angiotensin converting enzyme inhibitors with similar structure and metabolism (that is, enalapril and perindopril). Low dose perindopril seems to be less likely to cause hypotension in patients with heart failure. The explanation for the differences is unclear but may reflect differential effects on local tissue angiotensin generation.
比较老年稳定型慢性心力衰竭患者对低剂量血管紧张素转换酶抑制剂（卡托普利、依那普利和培哚普利）的首剂反应。
对老年稳定型慢性心力衰竭患者进行双盲、随机、安慰剂对照、平行分组前瞻性研究。
综合医院住院部，用于监督利尿剂撤药（24 - 48小时）并开始血管紧张素转换酶抑制剂治疗。
48例未经挑选的老年（58 - 85岁）患者，有症状但病情稳定的慢性心力衰竭（纽约心脏病协会II - IV级），经临床病史、检查和心脏检查确诊。患者书面知情同意在双盲条件下接受初始治疗；监测血压并采集血样以测量药代动力学和神经激素反应。
患者随机接受每日口服安慰剂、卡托普利（6.25毫克）、依那普利（2.5毫克）或培哚普利（2毫克）。
血压和心率反应、药物浓度以及血浆肾素和ACE活性。治疗组间差异采用方差分析。
四组随机分组的患者年龄、心力衰竭严重程度（纽约心脏病协会分级）、治疗前利尿剂剂量、血浆肾素活性和血清电解质状态相似。安慰剂治疗导致血压出现适度但显著的日间下降。卡托普利使血压在早期（1.5小时）出现显著且短暂的下降。依那普利导致的血压下降较晚（4 - 10小时），持续时间更长，且与仰卧位心率显著减慢有关。尽管培哚普利产生的血浆ACE抑制作用与依那普利相似，但它仅引起与安慰剂相似的血压变化。
这项对照研究首次表明，结构和代谢相似的血管紧张素转换酶抑制剂（即依那普利和培哚普利）在急性反应上存在质的差异。低剂量培哚普利似乎在心力衰竭患者中引起低血压的可能性较小。差异的原因尚不清楚，但可能反映了对局部组织血管紧张素生成的不同影响。
