雷米普利和卡托普利治疗心力衰竭引发首剂低血压反应比较

目的观察雷米普利和卡托普利治疗充血性心衰引发低血压反应的差异。方法随机开放药物平行对照试验。对117例经选择的充血性心力衰竭患者(NYHAⅡ~Ⅳ级)随机接受雷米普利2.5mg,或卡托普利6.25mg,服药前每15分钟测血压1次,服药后10h内每0.5h测血压1次。血压由动态血压监测仪记录。结果平均动脉压的最大下降值分别为:雷米普利组(1.32±1.42mmHg),卡托普利组(6.25±1.37)两组相比差异有极显著性(P<0.01)。舒张压下降>10mmHg者:卡托普利组7例(12.73%),雷米普利3例(4.76%),卡托普利组2例出现症状性低血压反应。结论雷米普利在首次用于充血性心力衰竭的治疗时安全、不易产生低血压反应。     

血管紧张素转换酶抑制剂治疗慢性心力衰竭首剂低血压反应的临床研究

目的　了解血管紧张素转换酶抑制剂 (ACEI)首剂应用时的低血压反应。方法　观察 4 0例慢性心力衰竭患者 ,其中培哚普利 (Perindopril)组首剂服 2mg、苯那普利(Benazepril)组 2 5mg、依那普利 (Enalapril)组 2 5mg及对照组 ,测基础及首剂服药后 0 5h、1h、2h、3h、4h、5h、6h的血压。结果　各组收缩压最大下降值 ,培哚普利为 6 0± 2 0mmHg。苯那普利为 5 8± 3 2mmHg。依那普利为 6 1± 4 0mmHg ,对照组为 (3 5± 3 8)mmHg ,各ACEI组均有血压下降 ,但组间无显著性差异 ,未见症状性低血压反应。结论　慢性心力衰竭首剂ACEI时虽有血压下降 ,但未见有首剂综合征的临床表现 ,故初步认为ACEI首剂应用于慢性心力衰竭是安全的。     

心力衰竭患者应用培哚普利与卡托普利的首剂低血压反应比较

目的　观察心力衰竭 (心衰 )患者对小剂量血管紧张素转换酶抑制剂的首剂低血压反应。方法　采用多中心、随机、平行对照的研究 ,16 7例 (5 9～ 91岁 )的心衰患者 (左室射血分数≤4 0 % )随机接受 2mg的培哚普利 (89例 )或 6 2 5mg的卡托普利 (78例 )治疗。应用动态血压监测用药前 2h及用药后 8h的血压改变。结果　以平均动脉压下降≥ 2 0mmHg(1mmHg =0 133kPa)和收缩压 <90mmHg定义为首剂低血压反应 ,培哚普利组的发生率明显低于卡托普利组 (10 1%与2 0 5 % ,P <0 0 5 )。培哚普利组最大的收缩压下降明显小于卡托普利组 [(19 2± 15 7)mmHg与(2 4 9± 17 6 )mmHg ,P =0 0 2 6 ]。所有的首剂低血压反应均无症状 ,仅通过动态血压监测发现。首剂低血压的发生与既往心肌梗死病史有关 ,合并陈旧性心肌梗死的心衰患者首剂低血压的发生率高于无心肌梗死病史的心衰组 (34 8%与 12 2 % ,P <0 0 1)。结论　培哚普利 2mg应用于心衰患者的首剂低血压发生率较低 ,培哚普利是一个相对安全的药物。合并陈旧性心肌梗死的心衰患者是发生首剂低血压的易患人群。     

培哚普利对充血性心力衰竭患者血压的影响

目的 :探讨培哚普利对充血性心力衰竭 (CHF)患者血压的影响 ,并对治疗前后血生化指标进行对比研究。方法 :将 6 2例CHF患者随机分为 3组 ,分别口服卡托普利首剂 6 .2 5mg ,2 4h后12 .5mg ,每日 3次 ;培哚普利首剂 2mg ,2 4h后 4mg ,每日 1次 ;安慰剂 1粒 ,每日 3次 ,均连服 2周。 结果 :首剂卡托普利使平均动脉压(MAP)降低 (16 .8± 2 .0 )mmHg(1mmHg =0 .133kPa) ,培哚普利作用不明显 ;2周后 ,卡托普利使卧位MAP降低(13.0± 2 .0 )mmHg ,立位降低 (16 .0± 3.0 )mmHg ,培哚普利使卧位MAP降低 (4.0± 2 .0 )mmHg ,立位降低 (6 .0± 2 .0 )mmHg(P <0 .0 1)。表明卡托普利首剂降压明显 ,而培哚普利无首剂降压反应 ,出现平缓的舒张压降低作用。结论 :培哚普利降压作用平缓 ,可作为CHF降压作用较为理想的药物之一 ,亦适合老年患者     

培哚普利和依那普利治疗充血性心力衰竭患者首剂低血压反应差异的随机对照研究

培哚普利和依那普利治疗充血性心力衰竭患者首剂低血压反应差异的随机对照研究     

培哚普利对充血性心力衰竭患者的影响

目的：观察培哚普利对充血性心力衰竭患者的影响。方法：对30例充血性心力衰竭患者在常规强心、利尿、扩血管治疗基础上，加用培哚普利；另外30例充血性心力衰竭患者为对照组，进行常规抗心力衰竭治疗。比较两种方法治疗心力衰竭后心功能的变化。结果：治疗组心功能改善总有效率（93．3％），左室射血分数（58％），明显高于对照组（P〈0．05）。结论：培哚普利对充血性心力衰竭患者能明显改善心功能，心力衰竭的症状。     

培哚普利治疗充血性心力衰竭的临床观察

目的:研究培哚普利(商品名：雅施达)对充血性心力衰竭的临床近期及远期预后疗效。方法:充血性心力衰竭患者98例，随机分为A、B两组，A组50例给予培哚普利2—6mg，每天1次，B组48例为对照组。出院后坚持口服药物治疗，并定期(半年)门诊随访1—2年。于治疗前、出院前、出院后(每年)做超声心动图，评价心功能，判定生活质量，并统计病死率。结果:培哚普利可使充血性心力衰竭患者的近期心功能明显改善。随访1—2年培哚普利组患者的生活质量明显优于对照组，病死率较对照组亦降低。结论:充血性心力衰竭患者长期坚持使用培哚普利可使心功能改善、生活质量提高、病死率降低、预后改善。     

培哚普利对自发性高血压大鼠内源性一氧化碳的影响

目的探讨培哚普利对自发性高血压大鼠(SHR)内源性一氧化碳(CO)产生的影响。方法选取自发性高血压大鼠(SHR)及年龄、体质量相匹配的正常血压(WKY)大鼠各16只,随机各分为培哚普利组和对照组(各8只),胃内分别注入培哚普利2mg/(kg.d)或等量生理盐水14d,于试验开始前一天和结束当天分别采血,应用连二亚硫酸钠将血液中的多组分血红蛋白还原为血红蛋白(Hb)和碳氧血红蛋白(COHb),用双波长分光光度法测定全血420nm和432nm的吸光度,计算出COHb的百分含量,并用放射免疫技术检测血浆中血管紧张素Ⅱ(AngⅡ)的水平。结果培哚普利治疗后,WKY大鼠血压、AngⅡ及COHb百分含量无变化;但SHR血压及血浆AngⅡ含量明显降低[SHR组收缩压:培哚普利组:(153.5±10.1)比对照组:(170.6±11.4)mmHg,P<0.01;SHR组AngⅡ:培哚普利组:(427.7±31.7)比对照组:(529.7±40.5)pg/mL,P<0.01],培哚普利还明显升高COHb百分含量[SHR组COHb:培哚普利组:(1.40±0.14)%比对照组:(1.28±0.10)%,P=0.01]。SHR培哚普利组用药后较用药前血压和AngⅡ明显降低(P<0.05),而COHb百分含量明显升高[(1.40±0.14比1.29±0.16)%,P=0.001],实验结束时SHR培哚普利组和对照组COHb含量与AngⅡ浓度均呈负相关(r分别为-0.54和-0.49,P<0.05)。结论培哚普利可能通过抑制AngⅡ的生成,使内源性CO的产生增加。     

比较伊贝沙坦与培哚普利对充血性心力衰竭患者细胞因子和血管紧张素II的影响

目的:比较伊贝沙坦与培哚普利对充血性心力衰竭（CHF）患者血清肿瘤坏死因子α（TNFα）、白细胞介素6（IL6）、血浆血管紧张素II（AngII）的影响。方法:测定健康对照者38例和CHF患者83例治疗前、后TNFα、IL6和AngII浓度。CHF患者83例随机分为伊贝沙坦组（n=43）和培哚普利组（n=36）,4例不能耐受而退出。治疗前及治疗后8周用彩色多普勒二维超声显像仪测定左心室射血分数（LVEF）。结果:CHF组血清TNFα、IL6和血浆AngII水平显著高于健康对照组（P<0.01）。血清TNFα、IL6水平与CHF的原发病无相关,而与LVEF呈负相关（r=-0.56,r=-0.60,P<0.01）,伊贝沙坦组、培哚普利组治疗8周后TNFα、IL6水平显著下降,伊贝沙坦降低IL6较培哚普利显著（P<0.05）,LVEF显著提高（P<0.05）。结论:CHF患者血清TNFα、IL6、AngII水平显著升高,且与LVEF呈负相关。伊贝沙坦及培哚普利具有降低血清TNFα、IL6水平及改善LVEF的作用。伊贝沙坦降低IL6较培哚普利显著,且耐受性好。     

培哚普利对心衰患者心律失常的治疗作用

在血管紧张素转换酶抑制剂（ＡＣＥＩ）培哚普利使用后，观察心功能及心律失常的变化，以明确ＡＣＥＩ对充血性心力衰竭（ＣＨＦ）患者心律失常的治疗作用。ＣＨＦ患者３５２例随机分为培哚普利组（Ｔ组）和对照组（Ｃ组），Ｔ组在Ｃ组基础上加用培哚普利２ｍｇ／ｄ￣４ｍｇ／ｄ，分别在用药及用药后４个月、１２个月、２４个月进行２４ｈＨｏｌｔｅｒ、心脏二维超声检查测定心功能及左室形态变化。结果Ｔ组４个月、１２个月、２４个     

First-dose hypotension after angiotensin-converting enzyme (ACE) inhibitors in chronic heart failure: a comparison of enalapril and perindopril. Slovak Investigator Group

BACKGROUND: First-dose hypotension refers to an observed reduction in blood pressure after the administration of the first dose of ACE inhibitors in patients with congestive heart failure. AIM: To compare the first-dose responses of low-dose enalapril and perindopril in patients with stable symptomatic chronic heart failure. METHODS: Single blind, randomised, multicenter, parallel, prospective study. Patients (N=298) with chronic heart failure due to ischemic heart disease or dilated cardiomyopathy, NYHA II-IV, ejection fraction<40%, age>18 years, naive to ACE inhibitors or ATI-receptor blocker, were randomised to receive a single dose of 2. 5 mg enalapril or 2.0 mg perindopril. Baseline laboratory and clinical examinations were performed before entry into the study. Ambulatory blood pressure monitoring started 2 h before the study medication was given, and continued for at least 10 h after the medication. RESULTS: The maximum drop in blood pressure appeared approximately 4 h after dose administration in both groups, and was more pronounced in the enalapril group. Patients in the enalapril group had a significantly higher incidence of asymptomatic hypotension. No symptomatic hypotension requiring a change in medication or a prolongation of hospitalisation was observed. CONCLUSION: A low dose of perindopril is well-tolerated at initiation of ACE inhibitor therapy in patients with chronic heart failure and causes less first-dose hypotension than a low dose of enalapril.     

A Comparative Study of the First Dose Hypotensive Effects of Captopril and Perindopril in Patients with Heart Failure

Angiotensin converting enzyme (ACE) inhibitors reduce morbidity and mortality in patients with heart failure and are a first-line therapy for chronic heart failure. However, the first-dose may be associated with asymptomatic or symptomatic hypotension. In previous small series with different ACE inhibitors, different blood pressure responses have been reported. We defined hypotension as a fall in mean blood pressure 20 mm Hg and an absolute value of systolic blood pressure 90 mm Hg and diastolic blood pressure 60 mm Hg. We studied the evolution of mean, systolic and diastolic blood pressure after initiation of perindopril and captopril treatments in a multicentre, double-blind, randomised, comparative, prospective study. One hundred seventy-six patients, mean age 64.9 ± 12.1 years, 116 men, with symptomatic heart failure, NYHA class II–IV, and a left ventricular ejection fraction <40%, were randomised to receive a single dose of captopril 6.25 mg (n = 85) or perindopril 2 mg, (n = 91). Systolic and diastolic blood pressure were recorded with Dinamap every 15 minutes during a baseline period of 2 hours, every 30 minutes from 2 to 7 hours and at 8 hours after the drug administration. Baseline characteristics of both groups were similar (demography, heart failure aetiology, NYHA class and blood pressure). Throughout the study there were 23 asymptomatic episodes of hypotension in the captopril group and 6 in the perindopril group (p = 0.039). One patient in the captopril group had symptomatic episodes.Mean blood pressure falls were significantly higher in the captopril versus perindopril group at 60 minutes (–4.6 mm Hg vs +0.7 mm Hg; p = 0.004), 75 minutes (–4.4 mm Hg vs –1.1 mm Hg; p = 0.042), and 180 minutes (–3.4 mm Hg vs +0.0 mm Hg; p = 0.042).When elderly patients (70 years) were considered the same pattern of response was found. In summary, first-dose hypotension is not negligible on initiation of therapy with ACE inhibitors in heart failure patients with low ejection fraction. Perindopril results in significantly less reduction in blood pressure and a lower incidence of symptomatic or asymptomatic hypotensive episodes and allows a safer start of therapy than captopril in heart failure patients.     

Effect of twelve-month combined therapy with perindopril and indapamide on the level of blood pressure and left ventricular hypertrophy in patients with hypertensive disease

Left ventricular hypertrophy (LVH) in patients with hypertensive disease is associated with unfavorable prognosis. Long term and effective antihypertensive therapy is capable to cause reverse development of LVH. We included in this study 72 patients (27 men, 45 women, age from 34 to 72 years) with untreated 1st and 2nd degree arterial hypertension (systolic blood pressure 140-179 mm Hg and/or diastolic blood pressure 99-109 mm Hg) and echocardiographical signs of LVH (left ventricular myocardial mass index >120 g/m2 in men and >100 g/m2 in women). After that the patients were randomized into 2 groups: the study group (39 patients, mean age 53.0+/-11.6 years) received combination of perindopril and indapamide in initial dose of 2 mg/0.625 mg, and comparison group (33 patients, mean age 54.4+/-8.2 years) received monotherapy with enalapril (10 mg). Once daily dosing of the preparation provided high level of compliance of patients with treatment. During 12-month therapy with combination of perindopril and indapamide target blood pressure (<140/90) was achieved in 74.4% of patients, during monotherapy with enalapril--in 27.3% of patients. Significant decrease of left ventricular myocardial mass index (LVMMI) with combination therapy was observed by 6th month of treatment (from 260 to 234 g), with monotherapy within same period of time--from 267 to 260 g. As a result of 12 months therapy of patients with I-II degree of hypertension with perindopril and indapamide LVMMI decreased by 17.5% while monotherapy with enalapril was associated with 5.6% decrease of LVMMI. Lowering of LVMMI occurred mainly at the account of decrease of left ventricular wall thickness.     

Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER

Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.     

Initial blood pressure response to enalapril in hospitalized patients (Studies of Left Ventricular Dysfunction [SOLVD]).

Studies of Left Ventricular Dysfunction (SOLVD) is a randomized trial of enalapril versus placebo in reducing mortality in patients with cardiac dysfunction (defined as left ventricular ejection fraction less than or equal to 35%). Before randomization, patients at risk for hypotension were hospitalized for a test dose of 2.5 mg of enalapril administered orally at baseline and again 12 hours later. As of February 1989, 89 of 7,539 (1.2%) patients had been studied during hospitalization. Baseline systolic and diastolic blood pressures were 115 +/- 18 and 73 +/- 10 mm Hg, respectively. After enalapril, systolic blood pressure decreased slightly but significantly 8 to 20 hours after the initial dose (mean reduction 8 to 11 mm Hg). In this highly selected group of 89 patients, symptoms relating to decrease in blood pressure were noted in 13 (15%). It is emphasized that most patients with cardiac dysfunction readily tolerate enalapril. However, the agent should be administered with caution to patients with advanced congestive failure and diminished baseline blood pressure, owing to a significant incidence of symptomatic hypotension.     

Antihypertensive Utility of Perindopril in a Large, General Practice-Based Clinical Trial

The authors evaluated, in a community-based open-label trial, the effectiveness and safety of perindopril in 13,220 US hypertensive patients and studied how physicians adhere to hypertension treatment guidelines. Patients received perindopril 4 mg q.d. for 6 weeks. Based on physicians' perception of blood pressure response, the patient was either maintained on 4 mg or the dose was increased to 8 mg for an additional 6 weeks. From baseline to week 12, the mean sitting blood pressure significantly declined from 156.9/94.5 mm Hg to 139.2/84.0 mm Hg. Further dose titration resulted in a clinically significant reduction in blood pressure in all patients with inadequate response on 4 mg at week 6. Blood pressure control (<140/<90 mm Hg) was achieved at 12 weeks in 48.8% patients. The subpopulation analyses demonstrated that perindopril monotherapy was effective in both men and women, in patients of all ethnicities, and in patients <65 and ≥65 years of age. Perindopril was safe and well tolerated in all hypertensive subgroups including high-risk patients. Physicians were more attuned to controlling diastolic than systolic blood pressure, and their adherence to the treatment guidelines was found to be not optimal.     

Antihypertensive utility of perindopril in a large, general practice-based clinical trial

The authors evaluated, in a community-based open-label trial, the effectiveness and safety of perindopril in 13,220 US hypertensive patients and studied how physicians adhere to hypertension treatment guidelines. Patients received perindopril 4 mg q.d. for 6 weeks. Based on physicians' perception of blood pressure response, the patient was either maintained on 4 mg or the dose was increased to 8 mg for an additional 6 weeks. From baseline to week 12, the mean sitting blood pressure significantly declined from 156.9/94.5 mm Hg to 139.2/84.0 mm Hg. Further dose titration resulted in a clinically significant reduction in blood pressure in all patients with inadequate response on 4 mg at week 6. Blood pressure control (<140/<90 mm Hg) was achieved at 12 weeks in 48.8% patients. The subpopulation analyses demonstrated that perindopril monotherapy was effective in both men and women, in patients of all ethnicities, and in patients <65 and ≤65 years of age. Perindopril was safe and well tolerated in all hypertensive subgroups including high-risk patients. Physicians were more attuned to controlling diastolic than systolic blood pressure, and their adherence to the treatment guidelines was found to be not optimal.     

Antihypertensive efficacy of the ACE-inhibitor perindopril in the elderly

To assess the antihypertensive efficacy of the angiotensin-converting enzyme (ACE)-inhibitor, perindopril, in the elderly, patients >65 years of age with supine diastolic blood pressure (BP) > or =90 and < or =110 mm Hg at the end of a 4-week placebo washout period were treated with perindopril 4-8 mg/daily vs placebo using a multicentre, randomised, double-blind, parallel group design. Of the 191 patients entered, 183 completed 8 weeks of double-blind therapy. Average age was 72-73 years. Supine and standing BP at the end of the placebo run-in period were 173/96 vs 168/96 mm Hg. BPs were measured in the morning, 20-25 h after the previous day's dose (ie, at the end of the dosing interval). In the placebo group, supine and standing diastolic BP decreased by 3-4 mm Hg, and systolic BP by 6-7 mm Hg. In the perindopril-group, diastolic BP decreased by 6-7 mm Hg and systolic BP by 10-13 mm Hg (both P < 0.01 vs placebo). These data indicate a substantial placebo response of particularly systolic BP in older hypertensives and indicate the importance of a parallel placebo-group to assess the extent of the actual drug's effect. Perindopril caused additional decreases in diastolic BP by about 2 mm Hg, and in systolic BP by 4-5 mm Hg. The extent of this drug-effect may be less in older vs middle-aged hypertensives.     

Differences in first dose response to angiotensin converting enzyme inhibition in congestive heart failure: a placebo controlled study.

OBJECTIVE--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. DESIGN--Double blind, randomised, placebo controlled, parallel, group prospective study of elderly patients with stable chronic heart failure. SETTING--General hospital in-patient admissions for supervised diuretic withdrawal (24-48 hours) and the introduction of angiotensin converting enzyme inhibitor therapy. PATIENTS--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. INTERVENTION--Patients were randomised to receive a daily oral dose of placebo, captopril (6.25 mg), enalapril (2.5 mg), or perindopril (2 mg). MAIN OUTCOME MEASURES--Blood pressure and heart rate responses, drug concentration, and plasma renin and ACE activities. Differences between treatment groups were analysed by analysis of variance. RESULTS--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. CONCLUSIONS--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.     

Differences in first dose response to angiotensin converting enzyme inhibition in congestive heart failure: a placebo controlled study.

OBJECTIVE--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. DESIGN--Double blind, randomised, placebo controlled, parallel, group prospective study of elderly patients with stable chronic heart failure. SETTING--General hospital in-patient admissions for supervised diuretic withdrawal (24-48 hours) and the introduction of angiotensin converting enzyme inhibitor therapy. PATIENTS--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. INTERVENTION--Patients were randomised to receive a daily oral dose of placebo, captopril (6.25 mg), enalapril (2.5 mg), or perindopril (2 mg). MAIN OUTCOME MEASURES--Blood pressure and heart rate responses, drug concentration, and plasma renin and ACE activities. Differences between treatment groups were analysed by analysis of variance. RESULTS--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. CONCLUSIONS--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.