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At least 19 recordsLinked to original sources
PubMed1994

Perindopril plus nifedipine versus perindopril plus hydrochlorothiazide in mild to severe hypertension: a double-blind multicentre study. The Multicentre Study Group on Treatment Association with Perindopril.

Thiazide diuretics are considered as the choice drug to combine with ACE inhibitors for the treatment of hypertension. However, there is much evidence showing that the combination of ACE inhibitors with a calcium channel blocker is effective and safe. We compared the safety and efficacy of perindopril 8 mg once daily plus nifedipine SR 10 mg twice daily with perindopril 8 mg once daily plus hydrochlorothiazide (HCTZ) 12.5 mg once daily in a two phase three month study. After a one month placebo run-in period, patients whose DBP averaged 95-125 mmHg received perindopril 4 mg once daily for the first open phase (n = 524). After one month those whose DBP remained > 90 mmHg were prescribed perindopril 8 mg once daily for a second month. Among them, those whose DBP were still > 90 mmHg entered the second phase for one month, in a double-blind fashion. Fifty-three patients received HCTZ (BP: 161.2/99.2 +/- 2.0/0.9 mmHg), 57 received nifedipine (BP: 161.4/98.7 +/- 2.2/0.7 mmHg). Five patients withdrew due to side-effects, three patients in the perindopril plus nifedipine group and two in the perindopril plus HCTZ group. After one month there was a significant drop in BP (P < 0.01) in both groups: perindopril plus HCTZ (-13.9/-11.9 mmHg) and perindopril plus nifedipine (-12.1/-10.8 mmHg). Heart rate was not significantly modified: perindopril plus HCTZ (-1.30 beats/min), perindopril plus nifedipine (+0.54 beats/min). There were no significant difference between the two combinations for BP reduction and heart rate. The incidence of adverse experiences was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Perindopril as monotherapy in hypertension: a multicenter comparison of two dosing regimens. The Perindopril Study Group.

Perindopril erbumine, a new long-acting, non-sulfhydryl-containing angiotensin converting enzyme inhibitor, was evaluated in 289 patients with hypertension in a 16-week, double-blind, placebo-controlled dose-ranging study. After 4 weeks of single-blind placebo treatment, patients with supine diastolic arterial pressures from 95 to 114 mm Hg were randomized to receive placebo, 4 mg perindopril once daily, or 2 mg perindopril twice daily. The daily dose of perindopril was increased by 4 mg every 4 weeks to a maximum of 16 mg per day. Mean decreases in systolic and diastolic arterial pressure were greater with perindopril than with placebo (p < 0.05). The dose-response curve flattened after 8 mg per day, and there was no difference in arterial pressure reduction or in the percentage of responders between once- and twice-daily administration of perindopril. Adverse reactions with perindopril were generally mild and, with the exception of cough, were similar with placebo. The findings of this study indicate that perindopril is effective, well tolerated, and suitable for once-daily administration for the treatment of hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

A dose-response study of perindopril in hypertension: effects on blood pressure 6 and 24 h after dosing. Perindopril Multicentre Dose-Response Study Group.

OBJECTIVE: To examine the dose-response characteristics of perindopril at the time of its peak and trough antihypertensive effects, with the primary outcome measure being changes in diastolic blood pressure. DESIGN: After a four-week, single-blind placebo run-in, patients were randomly allocated to four doses of perindopril or placebo using a parallel group design. SETTING: Sixteen specialist centres in the United States. PATIENTS: Of 483 patients entered into the run-in phase, 293 were eligible for randomization to perindopril or placebo therapy, with 260 patients included in the final efficacy analysis. INTERVENTIONS: Eligible patients were randomized to 12 weeks of therapy with perindopril 2, 4, 8 or 16 mg or placebo. MAIN RESULTS: At the final visit, all doses of perindopril significantly (P < 0.05) lowered diastolic blood pressure compared with placebo. The ratio of changes in placebo-corrected diastolic blood pressure at 24 versus 6 h for perindopril 2, 4 and 8 mg was 1.0, 1.0 and 0.97, respectively. The maximum antihypertensive effect was seen with perindopril 8 mg, with the 16 mg dose providing no additional response. Changes in systolic and diastolic blood pressure were similar. CONCLUSIONS: Perindopril is most effective at doses of 4 and 8 mg once daily, with similar reductions in diastolic blood pressure present at 6 and 24 h after dosing.

Antihypertensive Agents↗
PubMed2006

Effects of angiotensin-converting enzyme inhibition with perindopril on left ventricular remodeling and clinical outcome: results of the randomized Perindopril and Remodeling in Elderly with Acute Myocardial Infarction (PREAMI) Study.

BACKGROUND: Angiotensin-converting enzyme inhibitors reduce mortality and remodeling after myocardial infarction in patients with left ventricular dysfunction. METHODS: Perindopril and Remodeling in Elderly With Acute Myocardial Infarction (PREAMI), a double-blind, randomized, parallel-group, multicenter, placebo-controlled study, determined whether similar benefits occur in elderly postinfarction patients with preserved left ventricular function. A total of 1252 patients 65 years or older with a left ventricular ejection fraction of 40% or higher and recent acute myocardial infarction were randomized to receive perindopril erbumine or placebo (8 mg/d) for 12 months. The combined primary end point was death, hospitalization for heart failure, or left ventricular remodeling. Secondary end points included cardiovascular death, hospitalization for reinfarction or angina, and revascularization. RESULTS: The primary end point occurred in 181 patients (35%) taking perindopril and 290 patients (57%) taking placebo, with a significant absolute risk reduction of 0.22 (95% confidence interval, 0.16 to 0.28; P<.001). A total of 126 patients (28%) and 226 patients (51%) in the perindopril and placebo groups, respectively, experienced remodeling. The mean increase in left ventricle end-diastolic volume was 0.7 mL with perindopril compared with 4.0 mL with placebo (P<.001). In the perindopril group, 40 deaths (6%) and 22 hospitalizations (4%) for heart failure occurred, whereas 37 deaths (6%) and 30 hospitalizations (5%) occurred in the placebo group. Treatment did not affect death, whereas the hospitalization rate for heart failure was slightly reduced (absolute risk reduction, 0.01; 95% confidence interval, -0.01 to 0.02). No treatment effect on other secondary end points was detected. CONCLUSION: We found that 1-year treatment with 8 mg/d of perindopril reduces progressive left ventricular remodeling that can occur even in the presence of small infarct size, but it was not associated with better clinical outcomes.

Aged↗
PubMed1994

Once daily perindopril versus slow release diltiazem in the treatment of mild to moderate essential hypertension. Canadian Study Group on Perindopril.

The efficacy and acceptability of the angiotensin-converting enzyme (ACE) inhibitor perindopril were compared with those of an established treatment for hypertension in Canada, slow release diltiazem. Hypertensive patients aged 18 to 64 years presenting a mean sitting diastolic blood pressure (DBP) between 95 and 110 mmHg inclusive were randomized if they were without any concurrent serious renal, hepatic, cardiac or psychiatric illnesses. A total of 49 of 83 patients qualified for randomization after four weeks on placebo; 23 were assigned to the perindopril treatment group and 26 to the diltiazem treatment group. Starting doses (4 mg od in the perindopril group and 120 mg [60 mg bid] in the diltiazem group) were increased to a maximum of 8 mg od in the perindopril group and to 360 mg (180 mg bid) in the diltiazem group if DBP remained above 90 mmHg. Hydrochlorothiazide was added at week 8 if goal blood pressure was not achieved with the maximum dose. Both groups were comparable at randomization; baseline systolic blood pressure (SBP)/DBP were 153/100 mmHg and 150/99 mmHg in the perindopril and diltiazem groups, respectively. A significant decrease in SBP/DBP was observed from the second week of treatment: -10/-8 mmHg in the perindopril group and -8/-8 mmHg in the diltiazem group. This fall in blood pressure was maintained throughout the duration of the trial: -13/-9 and -13/-11 mmHg for the perindopril and diltiazem groups, respectively, at week 12, at which time monotherapy was taken by over 80% of patients and compliance was consistently over 90%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

ACE-inhibition with perindopril in essential hypertensive patients with concomitant diseases. The Perindopril Therapeutic Safety Collaborative Research Group.

PURPOSE: Many hypertensive patients have other, usually long-term diseases. Antihypertensive therapy may interfere with these diseases and their therapies. In the present study, the possible interactions of the ACE-inhibitor perindopril with several of the most common long-term diseases was evaluated. PATIENTS AND METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, the effect of perindopril was evaluated in 490 patients with mild essential hypertension and any one of the following concomitant diseases: hyperlipidemia, type II diabetes mellitus, ischemic heart disease, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, chronic obstructive pulmonary disease, or degenerative joint disease treated with nonsteroidal anti-inflammatory drugs (NSAIDs). After a 3-week single-blind placebo run-in, the patients received either perindopril (4 mg/d) or matching placebo for 6 weeks. RESULTS: Blood pressure was effectively reduced by perindopril irrespective of the associated disease. The rate of spontaneously reported side effects was low. Treatment with perindopril was free from adverse interactions with the concomitant diseases and therapies. Moreover, favorable actions could be observed in patients with ischemic heart disease (reduction of maximal ST-segment depression during peak exercise and decrease in the number of angina attacks), in patients with proteinuria (decrease in albuminuria in patients with normal serum creatinine levels), and in patients with NSAID-treatment (increase in prostaglandin E2 concentration in gastric mucosa suggesting gastric cytoprotection). CONCLUSION: This trial shows that ACE-inhibition with perindopril represents a simple, safe, and effective short-term therapeutic option for the large proportion of patients with mild essential hypertension and concomitant diseases and therapies.

Adult↗
PubMed1992

Synthesis and ACE inhibitory activity of the stereoisomers of perindopril (S 9490) and perindoprilate (S 9780).

Perindopril, a powerful ACE inhibitor contains 5 chiral carbons, thus there is the possibility of 2(5) = 32 stereoisomers for the general structure 1. These 32 stereoisomers were synthesized by cross-coupling the 8 stereoisomers of perhydroindole 2-carboxylic acid benzylester with the 4 stereoisomers of 2-(1-carbethoxybutylamino) propionic acid 4, then hydrogenating the resulting benzylesters. Each stereoisomer of perindopril furnished by saponification the corresponding diacid stereoisomer 2 of perindoprilate which is the active form of perindopril. For each of the 32 stereoisomers 2 the in vitro ACE inhibitory potency (IC50) was determined. Four of them, including perindoprilate, had activities in the nanomolar range, and four more were ca. 10 x less active. The four acid esters 1 corresponding respectively to the four most active diacids 2 in vitro were studied (1 mg/kg via the oral route) for their in vivo activity in dogs. It could be concluded that p.o. absorption of the active acid esters 1 and their activation to the active diacid 2 depended only on the chiralities of the two ring junction carbons of the perhydroindole ring.

Administration, Oral↗
PubMed2004

Effects of perindopril-based blood pressure lowering and of patient characteristics on the progression of silent brain infarct: the Perindopril Protection against Recurrent Stroke Study (PROGRESS) CT Substudy in Japan.

Controversy persists as to whether reducing the blood pressure of patients with a history of stroke leads to an increased risk of silent brain infarct (SBI) and dementia. A total of 667 patients were randomized to receive the angiotensin-converting enzyme (ACE) inhibitor perindopril (4 mg daily), with or without the diuretic indapamide (2 mg daily) or matching placebo(s). Brain CT scanning was performed annually over the mean follow-up period of 3.9 years. Active treatment reduced the blood pressure (systolic/diastolic) by 5.2/2.6 mmHg over the follow-up period. A total of 119 new SBI were detected and 92% of them were lacunar type small infarcts. The frequency of reaching the primary end-point (recurrent symptomatic stroke or new SBI) was similar in the placebo group (26.5%) and in the active treatment group (25.9%). There was no significant difference in brain atrophy indices between two groups. In the subgroup with a history of large artery infarction, 7 out of 55 patients from the placebo group developed new SBI, while none of the 40 patients from the active treatment group did so (p = 0.020). The baseline diastolic blood pressure was significantly associated with the risk of new SBI (p = 0.004), but the stroke subtype was not. In conclusion, blood pressure-lowering with a perindopril-based regimen did not increase the risk of SBI and brain atrophy in patients with a history of stroke. The baseline diastolic blood pressure was an independent predictor of new SBI, but the index stroke subtype did not influence the risk of SBI.

Aged↗
PubMed2001

Perindopril: an updated review of its use in hypertension.

UNLABELLED: 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.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Short-term and long-term cardiovascular actions of different doses of perindopril in the rabbit.

Short-term (one week) and chronic (six week) cardiovascular effects of orally administered perindopril were examined in the rabbit to demonstrate if short-term results can predict chronic outcomes. In short-term treatment, five doses of perindopril were examined in random order separated by a one week recovery period in each of six rabbits. Two doses of perindopril which resulted in a moderate hypotensive effect (-14 mmHg) and no hypotensive effect, respectively, were then selected for long-term treatment. Each rabbit in the short-term study received perindopril in doses of 0.01, 0.06, 0.32, 1.8 and 10 mg kg-1 day-1 for a week at a time. Rabbits on long-term treatment received either 0.3 or 0.01 mg kg-1 day-1 perindopril for six weeks. All rabbits had their mean arterial blood pressure (MAP) and heart rate recorded throughout treatment. Plasma angiotensin I (AngI), perindoprilat, angiotensin converting enzyme (ACE) inhibition were also assayed. Perindopril treatment for one week produced a dose-dependent hypotensive effect with the threshold dose, 0.06 mg kg-1 day-1, producing a 6.5 +/- 1.8 mmHg fall in MAP. The highest dose (10.0 mg kg-1 day-1) produced a large fall in blood pressure of -29.6 +/- 4.2 mmHg. The 0.01 and 0.06 mg kg-1 day-1 doses of perindopril produced an average 2.65 fold increase in plasma AngI levels compared to the initial control. The three higher doses (0.32-10.0 mg kg-1 day-1) of perindopril produced an equivalent 5.7 fold increase in plasma AngI levels compared to the initial controls. However, over six weeks 0.01 mg kg-1 day-1 perindopril induced a similar decrease in MAP as the 30 fold higher dose (-9.3 mmHg compared to -11.7 mmHg,). This was in spite of a 3 fold difference in plasma perindoprilat concentrations between the high and low dose perindopril groups. Plasma ACE inhibition was > 80% with both doses of perindopril. The results indicate that while perindopril decreases MAP in a dose-dependent manner in short-term (one week) periods, over longer treatment times (six weeks) low concentrations of perindopril, non-hypotensive with short-term treatment, may be as anti-hypertensive as considerably higher doses.

Angiotensin I↗
PubMed2004

A systematic review and meta-analysis of the efficacy and safety of a fixed, low-dose perindopril-indapamide combination as first-line treatment of hypertension.

BACKGROUND: A low-dose combination of perindopril and indapamide may effectively reduce blood pressure (BP) in hypertensive patients, but some factors related to study design might have contributed to the between-group differences in the rate of reduction of BP observed in some trials. OBJECTIVE: The aim of this study was to systematically assess the efficacy and safety profiles (through review of randomized, controlled trials) of the fixed, low-dose combination perindopril 2 mg and indapamide 0.625 mg given as 1 tablet daily as first-line antihypertensive therapy in patients with mild to moderate hypertension. METHODS: We searched MEDLINE (1966-April 2003), EMBASE (1980-March 2003), BIOSIS (1999-December 2002), and the Cochrane Library, using the medical subject headings with the search terms perindopril, indapamide, hypertension, randomized controlled trials, randomly, random, randomization, perindopril-indapamide, essential hypertension, and primary hypertension. Additional articles were obtained from the reference lists of relevant reviews and papers. RESULTS: We reviewed 11 trials (5936 individuals). In 5 studies of perindopril-indapamide versus placebo, the between-group weighted mean differences (WMDs) for both systolic and diastolic BP (SBP and DBP, respectively) favored perindopril-indapamide (SBP, -9.03 mm Hg [95% CI, -9.54 to -8.52]; DBP, -5.09 mm Hg [95% Cl, -5.42 to -4.77]; both P < 0.01 for z score for overall effect). In 6 studies of perindopril-indapamide versus routine antihypertensives, the between-group WMDs for SBP and DBP favored perindopril-indapamide (SBP, -3.72 mm Hg [95% CI, -7.11 to 0.33], P = 0.03 for z score for overall effect; DBP, -1.71 mm Hg [95% CI, -2.27 to -1.16], P < 0.01 for z score for overall effect). Five studies compared perindopril-indapamide and placebo; in the remaining 3 studies, which assessed perindopril-indapamide versus routine antihypertensives, the between-group WMDs for SBP and DBP favored perindopril-indapamide (SBP, -4.00 mm Hg [95% CI, -6.54 to -1.47], P < 0.01; DBP, -1.02 mm Hg [95% CI, -1.73 to -0.31], P < 0.01). Adverse events and withdrawals were not significantly different between perindopril-indapamide, placebo, or routine antihypertensive drugs. CONCLUSION: The studies in our analysis consistently demonstrated that a fixed, low-dose perindopril-indapamide combination has a favorable safety profile and may be efficacious as first-line treatment for patients with mild to moderate essential hypertension.

Adult↗
PubMed1995

The influence of perindopril and the diuretic combination amiloride+hydrochlorothiazide on the vessel wall properties of large arteries in hypertensive patients.

OBJECTIVE: To compare the cardiovascular effects of 6 months of treatment with the angiotensin converting enzyme inhibitor perindopril and with the diuretic combination amiloride+hydrochlorothiazide, and to study possible persistence of observed treatment effects after discontinuation of antihypertensive therapy. DESIGN: A placebo run-in period preceded a 6-month active-treatment phase in 41 patients with essential hypertension, according to a double-blind, randomized, parallel-group design. Patients received either 4 mg perindopril or 2.5/25 mg amiloride+hydrochlorothiazide once a day. Patients were then studied for a 3-month single-blind placebo run-out period. RESULTS: After 6 months of treatment, systolic blood pressure was reduced significantly by perindopril (supine by 11%, sitting by 10%) and by amiloride+hydrochlorothiazide (supine by 8%, sitting by 12%). Diastolic blood pressure was also decreased significantly by perindopril (supine by 8%, sitting by 11%) and by amiloride+hydrochlorothiazide (supine by 4%, sitting by 9%). Mean arterial pressure decreased significantly during treatment with perindopril (by 9%) and with amiloride+hydrochlorothiazide (by 6%). Cardiac index increased with perindopril (by 6%), because of an increased stroke index (by 5%), but amiloride+hydrochlorothiazide did not change cardiac function. Systemic vascular resistance index decreased significantly more with perindopril (by 14%) than with amiloride+hydrochlorothiazide (by 8%). The distensibility of the common carotid artery was significantly enhanced by perindopril (by 16%), but not changed by amiloride+hydrochlorothiazide (1% difference). The difference between perindopril and amiloride+hydrochlorothiazide for carotid distensibility was statistically significant. The compliance of the common carotid artery tended to be increased more by perindopril (by 7%) than by amiloride+hydrochlorothiazide, which induced a 5% decrease in carotid compliance. After withdrawal of therapy, for both drugs, all treatment-induced changes were reversed to pretreatment values within 7 weeks. CONCLUSION: The distensibility of the elastic common carotid artery was increased by perindopril, but not by amiloride+hydrochlorothiazide. Large-artery properties of the muscular arteries and systemic vascular resistance improved with both drugs, but in general the changes were more pronounced with perindopril than with amiloride+hydrochlorothiazide. The present results indicate a more pronounced effect of perindopril at both macro- and microcirculatory levels, which will consequently lead to a larger decrease in cardiac afterload. After discontinuation of therapy all parameters returned to baseline values within 7 weeks.

Adult↗
PubMed1992

Antihypertensive efficacy and safety of perindopril in mild-to-moderate essential hypertension: results of a double-blind multicenter study versus atenolol.

A 3-month double-blind multicenter trial compared the efficacy and safety of perindopril, a new angiotensin-converting enzyme (ACE) inhibitor, with atenolol in mild-to-moderate essential hypertension. A total of 190 patients, 49 of whom were diabetic, entered the perindopril-atenolol comparison. Of these, 163 had been previously treated and had a 4-week run-in period on placebo; 27 had previously been untreated and received placebo for 2 weeks. At entry, all patients who had a supine diastolic blood pressure (DBP) of 95-115 mm Hg were randomized to receive perindopril 2 mg or atenolol 25 mg, once daily. Patients were assessed at 2 weekly intervals for the first month and then monthly for 2 more months. If supine DBP was greater than 90 mm Hg, treatment was increased by stepwise doubling of dose up to 8 mg perindopril or 100 mg atenolol once daily, and later by the addition of hydrochlorothiazide 25 mg, (indapamide 2.5 mg in diabetic patients) once daily. The two groups were homogeneous prior to treatment except for supine and erect heart rate, which were higher in the perindopril group than in the atenolol group (p less than 0.05). Mean supine DBP was 101.1 +/- 0.6 mm Hg in the perindopril group (n = 94) and 99.9 +/- 0.6 mm Hg in the atenolol group (n = 96). After 3 months' active treatment, 74% of patients in the perindopril group achieved a supine DBP of less than or equal to 90 mm Hg and 73% of patients in the atenolol group achieved the same goal. Monotherapy controlled supine DBP in 67% of the perindopril group and 63% of the atenolol group. The decrease in supine DBP was not significantly different between the two groups (-12.9 +/- 0.9 versus -14.7 +/- 0.9 mm Hg) but the decrease in erect DBP was lower in the perindopril group (-10.3 +/- 0.9 versus - 13.4 +/- 1.0 mm Hg, p less than 0.02). Heart rate was reduced in the atenolol group (p less than 0.001). Sixteen patients withdrew from the study; nine were attributed to adverse events, two in the perindopril group and seven, including one death, in the atenolol group. Cough was spontaneously reported by 13% patients of the perindopril group and 1% patients of the atenolol group. In 5% of the perindopril cases this was mild and associated with upper respiratory tract infection. The nature and incidence of other symptoms were similar with both drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗