Perindopril. A review of its pharmacological properties and therapeutic use in cardiovascular disorders.

Perindopril is a long acting angiotensin converting enzyme (ACE) inhibitor, which displays similar pharmacodynamic properties to other agents in this class. In common with enalapril, it is also a prodrug. After absorption, perindopril is hydrolysed to the active metabolite, perindoprilat, and with once daily administration adequate 24-hour inhibition of ACE is obtained. Perindopril 4 to 8mg once daily is usually effective for blood pressure control in patients with mild to moderate essential hypertension. Those patients who do not respond adequately to monotherapy with perindopril usually respond with the addition of a second agent, such as a thiazide diuretic. General practice trials indicate that perindopril is at least as effective and as well tolerated as usual therapeutic dosages of captopril, atenolol or hydrochlorothiazide plus amiloride in mild to moderate essential hypertension. Preliminary results indicate that perindopril may also be effective in patients with severe hypertension or congestive heart failure. Perindopril is generally well tolerated and has an adverse effect profile similar to that of other ACE inhibitors. It further clinical experience confirms initial findings, perindopril is likely to represent a useful alternative to other members of the ACE inhibitor class in all grades of hypertension and congestive heart failure.     

Perindopril: an updated review of its use in hypertension

Perindopril erbumine (perindopril) is a prodrug ester of perindoprilat, an angiotensin converting enzyme (ACE) inhibitor. Perindopril 4 to 8 mg once daily significantly reduces supine systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline values in hypertensive patients. These reductions are maintained for at least 24 hours, as evidenced by trough/peak ratios of >50%. Vascular abnormalities associated with hypertension were improved or normalised during perindopril treatment. Perindopril 4 to 8 mg once daily significantly decreased carotid-femoral aortic pulse wave velocity (PWV), improved arterial compliance, reduced left ventricular mass index and, in patients with recent cerebral ischaemia and/or stroke, preserved cerebral blood flow despite significantly reducing SBP and DBP. Further research is needed to establish the significance of promising results showing that reductions in aortic PWV were associated with reduced mortality in patients with end-stage renal failure, a third of whom received perindopril. Response rates (numbers of patients with supine DBP < or = 90 mm Hg) were significantly higher with perindopril 4 to 8 mg once daily (67 to 80%) than with captopril 25 to 50 mg twice daily (44 to 57%) in 3 randomised double-blind trials. In other clinical trials, the antihypertensive effects of perindopril were similar to those of other ACE inhibitors (including enalapril) and calcium-channel antagonists. Combination treatment with perindopril and an antihypertensive agent from another treatment class provided additional benefits, either as first-line treatment or in patients failing to respond to monotherapy. Perindopril monotherapy was also effective in the elderly and in patients with hypertension and concomitant disease. Perindopril has a similar adverse event profile to that of other ACE inhibitors; cough is the most common event reported during treatment, and is also the most common adverse event responsible for treatment withdrawal. Conclusions: Perindopril is a well tolerated ACE inhibitor that is significantly better than captopril (in terms of response rates) in the treatment of hypertension, and as effective as other ACE inhibitors. Perindopril appears to reverse some of the vascular abnormalities associated with hypertension, including arterial stiffness and left ventricular hypertrophy, although further research is needed to confirm promising results regarding its ability to decrease associated cardiovascular morbidity and mortality. Results from ongoing studies will help confirm the place of perindopril in the treatment of hypertension; currently, it is an effective and well tolerated treatment for patients with mild to moderate essential hypertension.     

培垛普利联合螺内酯治疗慢性心力衰竭的临床疗效观察

目的:观察培垛普利联合螺内酯对慢性心力衰竭(CHF)患者心功能和BNP的影响.方法:84例CHF患者随机分为治疗组和对照组,在常规治疗病情基本稳定的基础上,加用培垛普利4 mg,1次,日和螺内酯20 mg.1次/日.观察治疗前后心功能、左室射血分数(EF)、血清脑钠索(BNP)测定及不良反应等.结果:治疗组的心功能疗效总有效率为71.4%.对照组为52.4%;两组患者用药后的左室EF值均较用药前有明显的提高,其提高值治疗组更显著.血清BNP明显下降(P<0.01).结论:长期应用培垛普利与小剂量螺内酯联合治疗慢性心衰远期临床疗效显著,且使用安全.     

Perindopril/indapamide 2/0.625 mg/day: a review of its place in the management of hypertension

The fixed low-dose combination of the ACE inhibitor perindopril and the non-thiazide diuretic indapamide has been evaluated in the management of patients with mild to moderate hypertension. Combination therapy aims to improve overall therapeutic efficacy while minimising adverse effects. In well-designed multicentre clinical trials, perindopril/indapamide at doses ranging from 2/0.625 to 8/2.5 mg/day was significantly more effective than placebo in achieving adequate blood pressure (BP) control. A similar reduction in supine BP was observed when combined perindopril/indapamide 2/0.625 mg/day was compared with losartan 50 mg/day or atenolol 50 mg/day. Similar reductions in 24-hour ambulatory BP were also seen with perindopril/indapamide 2/0.625 mg/day and irbesartan 150 mg/day. However, response and normalisation rates were significantly higher with combination therapy than with losartan or irbesartan monotherapy. Combined perindopril/indapamide 2/0.625 mg/day therapy effectively reduced BP in elderly patients aged 65 to 85 years to a significantly greater extent than either atenolol 50 mg/day or placebo. Supine BP was also normalised in approximately two-thirds of patients in a small noncomparative trial in patients with hypertension and renal impairment. Low-dose perindopril/indapamide 2/0.625 mg/day was well tolerated in clinical trials; the most common adverse events were headache and cough. Hypokalaemia, associated with the use of diuretics, occurred with a higher incidence with combined perindopril/indapamide 2/0.625 mg/day therapy than with either atenolol 50 mg/day or placebo. Perindopril/indapamide 2/0.625 mg/day has shown efficacy in well designed comparative trials with atenolol, losartan and irbesartan including elderly patients and patients with renal impairment. Studies comparing this dosage of perindopril/ indapamide with other combination therapies would be beneficial in allowing the place of perindopril/indapamide to be more accurately determined. The fixed-low dose combination of perindopril/indapamide provides a promising and well tolerated treatment option in the management of patients with mild to moderate hypertension.     

Haemodynamic and humoral effects of oral perindopril, an angiotensin converting enzyme inhibitor, in man.

The tolerance to and dynamic effects of 1 week's oral treatment with the angiotensin converting enzyme inhibitor, perindopril, were assessed in a placebo controlled, parallel group study in 36 normotensive males. The daily dose of perindopril was 1, 2, 4, 8 or 16 mg. The drug was well tolerated and produced no change in routine haematology or serum biochemistry tests. Dose related inhibition of plasma angiotensin converting enzyme was observed. Perindopril 16 mg produced 90% inhibition 4 h after dosing and 60% after 24 h. A dose related rise in plasma renin activity followed doses of 4 mg and over. The renin remained above the normal range for 24 h. Perindopril caused a modest lowering of plasma aldosterone levels but had no effect on plasma adrenaline or noradrenaline levels. Standing diastolic blood pressure was lowered, particularly with 16 mg daily of perindopril but only a slight rise in heart rate occurred. Perindopril appears to be a well tolerated inhibitor of plasma angiotensin converting enzyme, with predictable effects on the renin angiotensin system and blood pressure. An appropriate dose range for further study would appear to be 4 to 16 mg daily.     

The pharmacokinetics of perindopril and its effects on serum angiotensin converting enzyme activity in hypertensive patients with chronic renal failure.

1. Perindopril, an orally active angiotensin converting enzyme inhibitor, was given to 23 hypertensive patients with stable chronic renal failure for 15 days. The dose of perindopril was 2 or 4 mg once a day according to the degree of renal failure. The creatinine clearance of the patients ranged from 6 to 67 ml min-1 1.73 m-2. The pharmacokinetics of perindopril and perindoprilat, its active metabolite, were studied after acute and chronic administration of perindopril. 2. The drug was well tolerated and creatinine clearance was unaltered by treatment. 3. In both groups, steady-state was reached within 3 days of chronic treatment. 4. After both acute and chronic drug administration renal impairment had no effect on perindopril pharmacokinetics but the pharmacokinetics of perindoprilat were altered significantly. After chronic administration the serum accumulation ratio was 1.81 in patients with mild renal failure and 5.35 in patients with severe renal failure. Chronic administration did not modify the renal clearance of perindoprilat nor its elimination half-life. 5. A significant correlation between the renal clearance of perindoprilat and creatinine clearance was observed (r = 0.87 first dose, r = 0.83 last chronic dose). 6. A non-linear relationship between serum perindoprilat concentration and inhibition of angiotensin converting enzyme was described by a modified Hill equation. Values of IC50 were 1.11 +/- 0.07 micrograms I-1 (mean +/- s.d.) in patients with severe renal failure and 1.81 +/- 0.20 micrograms l-1 in patients with moderate renal failure. Chronic administration increased maximal inhibition and decreased the time to maximal inhibition only in patients with severe renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)     

曲美他嗪联合培哚普利治疗慢性充血性心力衰竭疗效观察

目的观察曲美他嗪（TMZ）联合培哚普利治疗慢性充血性心力衰竭（CHF）患者的临床疗效。方法72例CHF患者随机分为研究组和对照组，均给予内科常规抗心衰治疗。对照组加服培哚普利，初始剂量2mg，每日1次，逐渐加至靶剂量4mg，每日1次；研究组在对照组的基础上接受曲美他嗪20mg／次，3次/d。治疗12周。结果治疗12周，两组心功能较治疗前有明显改善，治疗组临床总有效率为93．4％，较对照组（80．6％）显著提高（P〈0．05）；超声心动图LVEF均较治疗前有明显改善（P〈0．01或P〈0．051．但治疗组较对照组改善更为显著（P〈0．05）。治疗组LVEDD、LVESD、LADD均较治疗前改善，差异有显著性（P〈0．01或P〈0．05），而对照组无改善；两组均未发现有明显的不良反应。结论TMZ联合培哚普利治疗CHF是一种安全有效的方法。     

培哚普利对充血性心力衰竭患者校正后QT离散度的影响

目的：观察培哚普利对充血性心力衰竭患者校正后ＱＴ离散度的影响。方法：造反确诊的充血性心力衰竭者４２例,随机分为治疗组和对照组。对照组使用强心剂、利尿剂及对症治疗;治疗组在此基础上加用培哚普利４～８ｍｇ;疗程均为３～４周。于治疗前及治疗后进行ＱＴ离散度的测定。结果：治疗组治疗后ＱＴｃｄ明显低于治疗前,而对照组治疗前后ＱＴｃｄ无明显变化。结论：培哚普利能有效地缩短心肌复极化的离散程度,有利于患者心肌电     

应用动态血压监测评价培哚普利治疗原发性高血压的降压疗效

目的：应用动态血压监测（ABPM）评估培哚普利（Perindopril）对轻、中度原发性高血压（EH）病人的24h降压效果。方法：轻、中度EH病人36例,服用2周安慰剂,坐位舒张压仍在95ˉ114mmHg者给与培哚普利4mg/d治疗8周。及治疗2、4、6、8周末测诊室血压,于服安慰剂末及治疗8周末应用ABPM。结果：培哚普利治疗8周,降压总有效率为83.3%;24h各时点血压均较治疗前显著下降（P＜0.01）不伴有心率及血压昼夜节律的改变;降低收缩压和舒张压的谷／峰值分别为80.6%和86.7%。结论：培哚普利能平稳、有效的控制EH病人24h血压,且病人总体耐受良好。     

Candesartan

Candesartan cilexetil is the prodrug of candesartan, an angiotensin II receptor antagonist. Candesartan binds selectively and non-competitively to the angiotensin II receptor type 1, thus preventing the actions of angiotensin II. Clinical trials have demonstrated its efficacy at a dose range of 2 to 32 mg once daily in hypertension of all grades, heart failure, in reducing urinary albumin excretion in diabetes mellitus and in coexisting hypertension and renal failure. Pharmacokinetic properties of candesartan cilexetil in elderly patients are not significantly different from those in younger individuals. Hepatic impairment does not change pharmacokinetics of candesartan cilexetil at doses up to 12 mg/day. No dose adjustment is necessary in patients with mild or moderate renal impairment. Tolerability of candesartan cilexetil is not much different from that of placebo. All adverse events are usually of mild to moderate severity and not dose-related. The most common adverse events were headache, upper respiratory tract infection, back pain, and dizziness. The incidence of these adverse effects, as well as of cough, was similar in patients treated with candesartan cilexetil or placebo. The incidence of adverse events in long-term trials was not different from that in short-term trials. Tolerability of candesartan cilexetil does not differ with either age or gender.     

Perindopril: a review of its use in patients with or at risk of developing coronary artery disease

Perindopril (Coversyl) is a prodrug ester of perindoprilat, an ACE inhibitor. This agent has shown pharmacodynamic effects beyond those responsible for lowering blood pressure (BP), including the improvement of endothelial function and the normalisation of vascular and cardiac structure and function. Perindopril has a well established role in the treatment of patients with hypertension or heart failure. In the EUROPA trial, once-daily perindopril 8 mg prevented cardiovascular events in patients with stable coronary artery disease (CAD) without any apparent heart failure receiving standard recommended therapy. In the ASCOT-BPLA trial, a calcium channel antagonist +/- perindopril regimen demonstrated significant cardiovascular benefits compared with a conventional beta-blocker +/- diuretic regimen in patients with hypertension who were at risk of developing cardiovascular events. These trials demonstrate that while perindopril, in addition to standard recommended therapy, has a potential role in preventing cardiovascular events in hypertensive patients, its role in the management of patients with stable CAD is clearly established.     

卡维地洛与培哚普利配伍治疗慢性充血性心力衰竭疗效观察

目的观察卡维地洛与培哚普利治疗慢性充血性心力衰竭(CHF)的疗效和安全性。方法将76例轻、中度慢性CHF患者随机分为2组,每组各38例,治疗组应用卡维地洛配伍培哚普利;对照组单用培哚普利。在心力衰竭标准用药的基础上,卡维地洛、培哚普利均由小剂量开始,逐渐递增至目标剂量。在12个月内检查超声心动图3次,以评价左室功能和容积。结果治疗后两组的左室射血分数(LVEF)均有增加,左室收缩末期容积(LVESV)和左室舒张末期容积(LVEDV)均减少,治疗组与对照组比较,有显著性差异(P<0.05)。治疗组有27例(71%)耐受目标剂量,其常见不良反应为头晕、咳嗽,两组不良反应情况无显著性差异(P>0.05)。两组均未发现肝肾功能损害或电解质、糖代谢变化。结论卡维地洛配伍培哚普利在心力衰竭标准用药的基础上治疗轻中度CHF患者安全、有效,可显著改善左室重塑。     

培哚普利与卡托普利治疗原发性高血压各60例的比较

目的 :比较培哚普利与卡托普利对原发性高血压的治疗作用。方法 :中度原发性高血压病人12 0例 ,随机分为 2组。培哚普利组 60例 (男性 4 5例 ,女性 15例 ;年龄 60±s 15a) ,采用培哚普利 4～ 8mg ,po ,qd× 4wk ;卡托普利组 60例 (男性 4 5例 ,女性 15例 ;年龄 60± 14a) ,采用卡托普利 12 .5～ 2 5mg ,po ,tid× 4wk。每组 16例进行了 2 4h动态血压监测。结果 :培哚普利组总有效率为92 % ,卡托普利组总有效率为 78% ,2组差异不显著(P >0 .0 5) ;不良反应发生率 ,培哚普利组 12 % ,卡托普利组 2 8% (P <0 .0 5) ,均轻微。结论 :培哚普利与卡托普利对中度高血压病疗效均较好 ,培哚普利组不良反应较少     

ANGIOTENSIN-CONVERTING ENZYME INHIBITION AS FIRST-LINE TREATMENT FOR HYPERTENSION

1. Perindopril (4 mg) was compared with atenolol (50 mg), captopril (25 mg b. d.) or a diuretic (hydrochlorothiazide 50 mg and amiloride 5 mg) in three studies involving a total of 503 hypertensive patients with a diastolic blood pressure (DBP) of 95–125 mmHg.
2. A 4 week single-blind placebo period preceded 12 weeks of active treatment. Dose titration was at weeks 4 and 8 if supine DBP >90 mmHg. The dose was doubled and if necessary a diuretic was added in the atenolol or captopril comparisons, and atenolol was added in the diuretic study.
3. The fall in supine blood pressure (BP) was 27/17 mmHg with perindopril and 21/16 mmHg for atenolol. Monotherapy controlled 55% of patients on perindopril and 48% on atenolol, increasing to 78% and 58% with the addition of hydrochlorothiazide, respectively. Captopril caused a BP fall of 19/12 mmHg compared with 27/18 mmHg for perindopril, with 49% of both groups being controlled on monotherapy.
4. Diuretic addition produced a greater antihypertensive effect with perindopril (75%) compared with 57% for captopril in achieving control. Perindopril caused a comparable fall in supine BP to the diuretic combination 27/19 mmHg and 31/18 mmHg, but the fall in erect systolic BP was significantly greater for the diuretic. At 3 months, 85% of the diuretic group and 78% of the perindopril group achieved the target BP.
5. A multicentre trial of 856 patients treated with perindopril (690 patients treated for 1 year or more) has shown that BP control is maintained in the long term with a low incidence of side-effects (7.9%) causing withdrawal from treatment. These studies demonstrate that perindopril compares favourably with standard first-line therapy for mild to moderate hypertension.     

Modulation of gentamicin nephrotoxicity by chronic inhibition of angiotensin-I-converting enzyme in rat

Perindopril, a new specific and potent inhibitor of angiotensin-I-converting enzyme, was used to evaluate the possible participation of inhibition of the renin-angiotensin system in the development of aminoglycoside-induced renal failure. Kidney function, morphology and biochemistry were evaluated at regular intervals throughout the study. Perindopril was given orally to rats at a daily dose of 2 mg/kg for 15 days prior to and during 15-day gentamicin treatment given intraperitoneally at a daily dose of 50 mg/kg. Perindopril treatment alone induced no modification in renal function or structure. Gentamicin treatment alone induced typical renal lesions which were scored as moderate and a slight but significant decrease in ACE blood levels. Concurrent treatment with perindopril and gentamicin induced a greater drop in ACE blood levels than after the administration of perindopril alone and produced more marked renal impairment than after the administration of gentamicin alone. These observations suggest that the integrity of the renin-angiotensin system may play an important role in limiting kidney injury during aminoglycoside-induced nephrotoxicity.     

Imidapril: a review of its use in essential hypertension, Type 1 diabetic nephropathy and chronic heart failure

Imidapril (Tanatril), through its active metabolite imidaprilat, acts as an ACE inhibitor to suppress the conversion of angiotensin I to angiotensin II and thereby reduce total peripheral resistance and systemic blood pressure (BP).In clinical trials, oral imidapril was an effective antihypertensive agent in the treatment of mild to moderate essential hypertension. Some evidence suggests that imidapril also improves exercise capacity in patients with chronic heart failure (CHF) and reduces urinary albumin excretion rate in patients with type 1 diabetes mellitus. Imidapril was well tolerated, with a lower incidence of dry cough than enalapril or benazepril, and is a first choice ACE inhibitor for the treatment of mild to moderate essential hypertension.     

Perindopril for control of blood pressure in patients with hypertension and other cardiovascular risk factors: an open-label, observational, multicentre, general practice-based study

BACKGROUND AND OBJECTIVES: Hypertension, one of the major treatable cardiovascular (CV) risk factors, usually occurs in association with other major risk factors. As well as providing rapid blood pressure (BP) goal attainment, antihypertensive therapy should also provide reductions in CV events and mortality in a wide range of patients. For this, higher dosages and combinations of antihypertensive agents are often required. ACE inhibitors are recommended as first-line agents for control of hypertension in patients with additional CV risk factors. The PEACH (Perindopril's Effect At Controlling Hypertension) study was a community-based study performed to evaluate the effectiveness and safety of high-dose perindopril in patients with mild-to-moderate hypertension and additional risk factors for CV disease. METHODS: This was an open-label, multicentre observational study conducted in Canadian general practice clinics. The study assessed the efficacy and tolerability of perindopril given once daily for 10 weeks uptitrated to the maximal recommended dose of perindopril as required for BP control in newly diagnosed or previously treated patients with uncontrolled mild to moderate hypertension and >or=1 additional risk factor. Patients not achieving target BP after 2 weeks of therapy were uptitrated from perindopril 4 mg to perindopril 8 mg once daily. Efficacy endpoints included reduction in systolic (SBP) and diastolic (DBP) BP and BP control. Tolerability assessments included adverse effects and physicians' assessment of tolerability. The number of missed doses was also recorded. RESULTS: Overall, 2220 patients with hypertension and >or=1 other risk factor were prescribed perindopril at 291 centres; 51.9% were male, 78.3% Caucasian, 12.8% Asian, 36.2%>or=65 years of age and 34.5% had uncontrolled BP despite previous antihypertensive treatment. Compared with previously treated patients, treatment-naive patients had fewer risk factors, and a higher proportion were Asian (p<0.05 for all comparisons). Most patients (76%) had 1-2 risk factors. Perindopril produced significant SBP/DBP reductions at 2 and 10 weeks (-15.8/-8.0 and -21.1/-11.0 mmHg, respectively). Overall, at week 10, BP control rate was 53.6%, better than at week 2 in the overall cohort and in all subgroups. Uptitration to high-dose perindopril to achieve BP control was required in 46% of patients with one additional risk factor compared with 64% of patients with >or=4 additional risk factors. These results demonstrate that the more risk factors the patient has, the greater the need for high-dose perindopril to achieve BP control. Perindopril was well tolerated as indicated by the high proportion of physicians (95.9%) reporting 'good' to 'excellent' tolerability at week 10. CONCLUSION: In this community-based clinical practice trial, up to 10 weeks' perindopril therapy, uptitrated to the maximal recommended dose as required for BP control, significantly reduced SBP/DBP in patients with mild-to-moderate hypertension and additional CV risk factors. Patients with more risk factors were more likely to require high-dose perindopril.     

培哚普利与贝那普利治疗左心心力衰竭的比较

目的 :比较培哚普利与贝那普利治疗心力衰竭的疗效。方法 :培哚普利组 4 0例 (男性 2 7例 ,女性 13例 ,年龄 67a±s10a)应用培哚普利 4mg ,po ,qd .贝那普利组 4 0例 (男性 2 7例 ,女性 13例 ,年龄 71a± 9a)应用贝那普利 10mg ,po ,qd。 2组疗程均为 4wk。结果 :培哚普利组抗心力衰竭有效率为 82 % ,贝那普利组抗心力衰竭有效率为 80 % ,2组间差异无显著意义 (P >0 .0 5)。 2药均有减轻心肌缺血、改善左室收缩功能作用。 2组副作用均轻微。结论 :培哚普利和贝那普利抗心力衰竭作用相近     

ACE inhibitors in heart failure--switching from enalapril to perindopril

Although ACE inhibitors have demonstrated their beneficial effects in heart failure, whether different agents may induce different benefits remains unclear. We designed an open, sequential, prospective study switching heart failure patients receiving enalapril to perindopril which has been reported to be longer acting and better tolerated. The objective of the study was to find out if clinical and functional status could be further improved by changing from enalapril 30 mg daily to a perindopril 4 mg daily. Assessments of clinical status, echocardiography and nuclear ventriculography were performed at baseline under enalapril (30 mg mean dose (b.i.d.)), then 6 and 12 months after the switch to perindopril (4 mg/day mean dose). Thirty-one patients were included (90% men, aged 56.5 +/- 11.8 years, mean radionuclide left ventricular (LV) ejection fraction 22.4 +/- 8.5 %). After 6 months of treatment, NYHA functional class was significantly improved; the percentage of patients in class I increased to 57% after perindopril versus 20% at baseline (p < 0.001), and 50% of the total study population gained at least one NYHA class. After 12 months of treatment, 80% of the patients were in NYHA class I. Blood pressure decreased significantly with a good tolerance at 6 months and then remained stable. After 12 months of treatment, significant reductions of LV end-diastolic diameter (61.4 +/- 5.3 vs. 64.5 +/- 6.5 mm; p = 0.001) and LV mass index (143.3 +/- 21.5 vs. 164.2 +/- 40.2 g/m2; p < 0.001) were observed, reflecting a positive effect on the LV remodelling process. Despite some limitations, because it is of an open-label design with a small number of patients, our study found significant differences in clinical and objective parameters in heart failure patients switched from enalapril to perindopril. The prognostic significance of these findings remains to be investigated.     

Ramipril. A review of its pharmacological properties and therapeutic efficacy in cardiovascular disorders

Ramipril is a long acting angiotensin converting enzyme (ACE) inhibitor, which exhibits similar pharmacodynamic properties to captopril and enalapril. Like enalapril it is a prodrug, which is hydrolysed after absorption to form the active metabolite ramiprilat which has a long elimination half-life, permitting once daily administration. In hypertensive patients daily doses in the range 2.5 to 20 mg are usually effective in reducing high blood pressure and maintaining satisfactory control during long term treatment. Patients who do not respond adequately to monotherapy with ramipril usually respond with the addition of a diuretic such as hydrochlorothiazide or piretanide. Ramipril 5 to 10 mg once daily shows comparable antihypertensive efficacy to usual therapeutic dosages of captopril, enalapril and atenolol in patients with mild to moderate essential hypertension. Preliminary data indicate that ramipril may be effective in indications such as severe essential hypertension and renal hypertension. It has also displayed beneficial effects in patients with moderate to severe congestive heart failure. Ramipril has been well tolerated and exhibits an adverse effect profile typical of ACE inhibitors as a class. In conclusion, ramipril will likely represent a useful alternative ACE inhibitor for use in patients with hypertension or congestive heart failure.