Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Perindopril”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1998

Effects of perindopril on vascular wall and left ventricular hypertrophy in rats with experimental hypertension.

The model of hypertensive rat was established by using the method of abdominal aortic constriction, 33 male SD rats were randomly divided into 4 groups: group A (sham-operated rats serving as controls), group B (hypertensive rats serving as controls), group C (hypertensive rats subjected to low-dose perindopril treatment, 0.1 mg.kg-1/d) and group D (hypertensive rats receiving high-dose perindopril treatment, 1.5 mg.kg-1/d). The drug was administered by gavage for 4 weeks. At the end of the treatment, mean arterious pressure (MAP) was measured via catheter in the carotid artery. The heart was taken and weighed to calculate the ratio of left ventricular weight to body weight (LVW/BW). The ratio of medial mean thickness to mean diameter of lumen of aorta and superior mesenteric artery was calculated by morphometry. Concentration of angiotensin II (A II) in plasma and in aortic wall were determined by radioimmunoassay (PA II, AA II). Our results showed that both high-dose and low-dose perindopril may prevent hypertrophy of left ventricle and hypertrophy of the tunica media of superior mesenteric artery. In addition, high-dose perindopril may significantly inhibit hypertrophy of aortic media. The above effects of perindopril may be explained by inhibition on tissue renin-angiotensin system of both vascular wall and heart, but is not related to circulating A II (PA II).

Angiotensin II↗
PubMed2004

Effects of the angiotensin-converting enzyme inhibitor perindopril on endothelial injury and hemostasis in rabbit endotoxic shock.

OBJECTIVE: To assess the effects of the angiotensin-converting enzyme (ACE) inhibitor (ACEI) perindopril on prolonged endothelial cell dysfunction in a rabbit endotoxic model. DESIGN: Randomized, controlled, interventional trial. SETTING: University animal laboratory. SUBJECTS: A total of 65 male New Zealand White rabbits, randomly assigned to one of eight groups. INTERVENTIONS: Endotoxic shock was induced by a single lipopolysaccharide (LPS, serotype O55:B5) bolus (0.5 mg.kg(-1), i.v., Escherichia coli endotoxin). Coagulation factors and expression of monocyte tissue factor (TF) were determined by functional assay. Endothelium-dependent vascular relaxation was assessed by in vitro vascular reactivity. Immunohistochemical staining (CD31) was performed to assess endothelial injury of the abdominal aorta. These parameters were studied 5 days (D5) after the onset of endotoxic shock. Rabbits were randomized to receive perindopril (1 mg kg(-1) day(-1) orally) alone, or with N(G)-nitro-L-arginine methyl ester (L-NAME; 15 mg kg(-1) day(-1) orally), or L-NAME alone initiated 7 days before the onset of endotoxic shock and maintained for 5 days afterward. MEASUREMENTS AND RESULTS: Perindopril prevented altered endothelium-dependent relaxation to acetylcholine induced by LPS injection (E(max)=75.6+/-3.7 vs 42.3+/-9.4% in LPS group, p<0.05). This effect was inhibited by co-treatment with L-NAME. Perindopril had no effect on either LPS-induced endothelial histological injury or monocyte TF expression. CONCLUSION: These data suggest that perindopril can prevent endothelial dysfunction in endotoxin-induced shock through an NO-dependent mechanism.

Analysis of Variance↗
PubMed2000

Amperometric biosensor based on D-aminoacid oxidase for the R-perindopril assay.

A new amperometric biosensor based on D-aminoacid oxidase is described for the assay of R-perindopril. R-perindopril can be determined in the 400-20 nmol/L concentration range; the detection limit is 10 nmol/L. The selectivity was checked with S-perindopril, D- and L-proline, and polyvinylpyrrolidone. The main interfering species was D-proline. An automated system for the assay of R-perindopril based on the concept of flow injection with an amperometric biosensor (based on D-aminoacid oxidase) as detector is also described. The system is suitable for the on-line monitoring of R-perindopril at a sampling rate of 72 samples/h, in the linear range: 100 nmol/L -20 nmol/L with an RSD better than 0.09% (n = 10).

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

A new trial of the efficacy, tolerability, and safety of angiotensin-converting enzyme inhibition in mild systemic hypertension with concomitant diseases and therapies. Perindopril Therapeutic Safety Study Group (PUTS).

A multicenter, double-blind, randomized, and placebo-controlled trial, the Perindopril Therapeutic Safety Study (PUTS), was designed to assess the interaction between angiotensin-converting enzyme (ACE) inhibition and the diseases and therapies commonly found associated with mild hypertension. A total of 480 male and female patients aged 30-70 years with a diastolic pressure of 90-104 mm Hg were included after a 3-week placebo run-in if they satisfied standard criteria for any of the following: hyperlipidemia, type II diabetes, ischemic heart disease, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, chronic obstructive lung disease or treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). At the end of the placebo run-in period, patients were randomly assigned to either placebo or perindopril 4 mg once daily. A total of 460 patients completed the 6-week double-blind phase, comprising 3 assessments at 1, 3, and 6 weeks. In this report, the principal results obtained in 5 disease groups (hyperlipidemia, type II diabetes, ischemic heart disease, nephropathy with proteinuria, and NSAID treatment) will be reported. A total of 269 patients belonging to one of the aforementioned 5 disease groups completed the double-blind phase of the study and were included for statistical evaluation. In the perindopril group, systolic and diastolic blood pressures decreased significantly more than in the placebo group, and a sitting diastolic blood pressure of 90 mm Hg was achieved in 65% of patients in the perindopril group and 30% of patients in the placebo group. The incidence of symptoms spontaneously reported by the patients was low: 2 patients of the perindopril group complained of cough.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Perindopril versus captopril: efficacy and acceptability in an Italian multicenter trial.

The aim of this 3-month, double-blind, double-dummy, parallel group study was to compare the antihypertensive efficacy and acceptability of perindopril (4-8 mg/day) in 54 patients (30 males, 24 females, 25-68 years of age) and captopril (50-100 mg/day) in 54 patients (39 males, 15 females, 29-66 years of age) in the treatment of essential hypertension. In a subgroup of 38 patients a complete echocardiographic study was performed. The two groups had similar (ANOVA) blood pressure (BP), heart rate (HR), body mass index, and duration of hypertension. Supine and standing BP was significantly reduced by both drugs, without differences between them. Owing to poor control of BP, hydrochlorothiazide (25 mg/day) was added to 27% of patients on perindopril and to 41% of patients on captopril (p less than 0.05). Normalization of supine diastolic BP (less than or equal to 90 mm Hg) was obtained in 67% of patients on perindopril and in 47% of patients on captopril (p less than 0.01). No change in HR was detected. Only mild untoward effects were recorded. Left ventricular mass was significantly reduced by either drug, with no change in systolic function. In conclusion, perindopril and captopril, at these doses, were both well tolerated and on average reduced BP to a similar extent; however, treatment with perindopril showed that fewer patients needed the addition of a thiazide and BP became normal in a larger number of patients.

Adult↗
PubMed2006

Effect of perindopril on renal medullary hemodynamics in genetically hypertensive rats.

BACKGROUND: Early and chronic angiotensin converting enzyme (ACE) inhibition prevents hypertension and improves the pressure natriuresis in Lyon hypertensive (LH) rats. The effect of this treatment on the responses of renal medullary blood flow (MBF) to angiotensin II (Ang II) was studied. METHODS: In chronic experiments, Ang II (7.5 to 480 ng/kg, intravenous) was injected in 15-week-old anesthetized LH and normotensive (LL) control rats treated orally since weaning with perindopril (0.4 or 1.5 mg/kg/day) with or without pretreatment with indomethacin (5 mg/kg intravenous). In acute experiment, Ang II (30 to 480 ng/kg intravenous) was given in LH rats treated acutely with perindopril (1.5 mg/kg, intravenous bolus). RESULTS: Administration of Ang II induced dose-dependent decreases in MBF, which were greater in LH than in LL rats. In LL rats, the initial and short-lasting (<1 min) medullary vasoconstriction evoked by Ang II was followed by a long-lasting (>2 min) and dose-dependent medullary vasodilation, which was blunted in LH rats. Chronic perindopril treatment normalized the blood pressure level in LH rats and corrected their blunted medullary vasodilation, whereas the same treatment had no significant effect in LL rats. In chronically perindopril-treated LH rats, indomethacin decreased by 90% the medullary vasodilation induced by Ang II. Acute perindopril treatment did not modify the medullary responses to Ang II in LH rats. CONCLUSIONS: Chronic ACE inhibition restores the vasodilator response of MBF to Ang II in LH rats. This effect, which is not observed after acute inhibition, is mainly mediated through the release of prostaglandins.

Angiotensin II↗
PubMed2001

Efficacy of perindopril in the treatment of systemic hypertension.

The angiotensin-converting enzyme inhibitor, perindopril erbumine, has been approved for use in the United States only recently but has been studied extensively worldwide over the last decade. Placebo-controlled trials in a wide range of patients with hypertension, including the elderly, those with isolated systolic hypertension, and those with concomitant diseases such as hyperlipidemia, diabetes, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, and chronic obstructive pulmonary disease, have shown that perindopril is highly effective in lowering both systolic and diastolic blood pressure (BP). Studies in which BP has been monitored for 24-hour intervals show that perindopril (1) has a gradual onset of action, (2) provides smooth BP control over its once-daily dosing interval, (3) has a trough-peak ratio of about 1, and (4) maintains its antihypertensive efficacy despite missed doses. Perindopril increases arterial compliance and reverses left ventricular hypertrophy in hypertensive patients. Both of these effects are at least partly independent of its ability to lower BP. Perindopril is safe and well tolerated in patients with hypertension. Rates of adverse events and discontinuation because of such events are low.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack.

BACKGROUND: Blood pressure is a determinant of the risk of stroke among both hypertensive and non-hypertensive individuals with cerebrovascular disease. However, there is uncertainty about the efficacy and safety of blood-pressure-lowering treatments for many such patients. The perindopril protection against recurrent stroke study (PROGRESS) was designed to determine the effects of a blood-pressure-lowering regimen in hypertensive and non-hypertensive patients with a history of stroke or transient ischaemic attack. METHODS: 6105 individuals from 172 centres in Asia, Australasia, and Europe were randomly assigned active treatment (n=3051) or placebo (n=3054). Active treatment comprised a flexible regimen based on the angiotensin- converting-enzyme inhibitor perindopril (4 mg daily), with the addition of the diuretic indapamide at the discretion of treating physicians. The primary outcome was total stroke (fatal or non-fatal). Analysis was by intention to treat. FINDINGS: Over 4 years of follow up, active treatment reduced blood pressure by 9/4 mm Hg. 307 (10%) individuals assigned active treatment suffered a stroke, compared with 420 (14%) assigned placebo (relative risk reduction 28% [95% CI 17-38], p<0.0001). Active treatment also reduced the risk of total major vascular events (26% [16-34]). There were similar reductions in the risk of stroke in hypertensive and non-hypertensive subgroups (all p<0.01). Combination therapy with perindopril plus indapamide reduced blood pressure by 12/5 mm Hg and stroke risk by 43% (30-54). Single-drug therapy reduced blood pressure by 5/3 mm Hg and produced no discernable reduction in the risk of stroke. INTERPRETATION: This blood-pressure-lowering regimen reduced the risk of stroke among both hypertensive and non-hypertensive individuals with a history of stroke or transient ischaemic attack. Combination therapy with perindopril and indapamide produced larger blood pressure reductions and larger risk reductions than did single drug therapy with perindopril alone. Treatment with these two agents should now be considered routinely for patients with a history of stroke or transient ischaemic attack, irrespective of their blood pressure.

Aged↗
PubMed2001

Comparison of spectrophotometric and an LC method for the determination perindopril and indapamide in pharmaceutical formulations.

A new sensitive, simple, rapid and precise reversed-phase high performance liquid chromatographic (HPLC) and two spectrophotometric methods have been developed for resolving binary mixture of perindopril and indapamide in the pharmaceutical dosage forms. The first method is based on HPLC on a reversed-phase column using a mobile phase of phosphate buffer pH 2.4 and acetonitrile (7:3 v/v) was used. Linearity range for perindopril and indapamide was 5.0-70.0 and 8.0-35.0 microg ml(-1). In the second method, the first derivative spectrophotometry with a zero-crossing technique of measurement is used for the simultaneous quantitative determination of perindopril and indapamide in binary mixtures without previous separation step. Linear calibration graphs of first derivative values at 225.7 and 255.4 nm for perindopril and indapamide, respectively. The third method is based on ratio derivative spectrophotometry, the amplitudes in the first derivative of the ratio spectra at 226.5 and at 255.3 nm were selected to determine perindopril and indapamide in the binary mixture. All the proposed methods showed good linearity, precision and reproducibility. The proposed methods were successfully applied to the pharmaceutical dosage forms containing the above-mentioned drug combination without any interference by the excipients.

Antihypertensive Agents↗
PubMed1998

Fixed low-dose perindopril-indapamide combination in hypertensive patients with chronic renal failure.

The angiotensin converting enzyme inhibitor perindopril and the diuretic indapamide have been shown to be effective antihypertensive agents in patients with chronic renal failure. A fixed low-dose combination of these two agents has been proposed in the treatment of hypertension. We evaluated this combination in 26 patients with mild to moderate essential hypertension and mild to severe chronic renal failure that did not require dialysis. This was a multicenter, open trial consisting of a 2-week single-blind placebo washout period followed by 12 weeks of active treatment. At week 0, the patients received 2 mg perindopril/0.625 mg indapamide once a day or every other day, with the possibility of dosage adjustment to perindopril 4 mg/indapamide 1.25 mg at week 2, week 4, or week 8. A pharmacokinetic analysis using a population pharmacokinetic approach was performed at week 8. Twenty-three patients completed the 12-week study, at which time 14 patients were receiving 2 mg perindopril/0.625 mg indapamide daily, three were receiving 2 mg perindopril/0.625 mg indapamide every other day, and six perindopril 4 mg/indapamide 1.25 mg. Blood pressure readings (supine) decreased from 170.4+/-19.2 / 101.5+/-6.7 mm Hg before active treatment to 146.5+/-19.7 / 86.5+/-10.6 mm Hg at the end of treatment (P < .0001). Pharmacokinetic analysis showed that for indapamide and perindoprilat (the active metabolite of perindopril) the area under the curve (AUC24) increased with the severity of renal failure. No interaction was noted between the two drugs. Mean serum creatinine and sodium and serum potassium levels remained stable during the study. Impairment of renal function occurred in one patient and was considered unrelated to treatment. We conclude that a fixed low-dose perindopril-indapamide combination as first-line treatment has a good safety/efficacy ratio in hypertensive patients with chronic renal failure.

Adolescent↗
PubMed2001

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 > or = 20 mm Hg and an absolute value of systolic blood pressure < or = 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 (> or =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.

Aged↗
PubMed1999

Perindopril, an angiotensin converting enzyme inhibitor, in pulmonary hypertensive rats: comparative effects on pulmonary vascular structure and function.

1. Hypoxic pulmonary hypertension in rats (10% O2, 4 weeks) is characterized by changes in pulmonary vascular structure and function. The effects of the angiotensin converting enzyme inhibitor perindopril (oral gavage, once daily for the 4 weeks of hypoxia) on these changes were examined. 2. Perindopril (30 mg kg-1 d-1) caused an 18% reduction in pulmonary artery pressure in hypoxic rats. 3. Structural changes (remodelling) in hypoxic rats included increases in (i) critical closing pressure in isolated perfused lungs (remodelling of arteries <50 microm o.d.) and (ii) medial wall thickness of intralobar pulmonary arteries, assessed histologically (vessels 30 - 100 and 101 - 500 microm o.d.). Perindopril 10 and 30 mg kg-1 d-1 attenuated remodelling in vessels < or = 100 microm (lungs and histology), 30 mg kg-1 d-1 was effective in vessels 101 - 500 microm but neither dose prevented hypertrophy of main pulmonary artery. 3 mg kg-1 d-1 was without effect. 4. Perindopril (30 mg kg-1 d-1) prevented the exaggerated hypoxic pulmonary vasoconstrictor response seen in perfused lungs from hypoxic rats but did not prevent any of the functional changes (i.e. the increased contractions to 5-HT, U46619 (thromboxane-mimetic) and K+ and diminished contractions to angiotensins I and II) seen in isolated intralobar or main pulmonary arteries. Acetylcholine responses were unaltered in hypoxic rats. 5. We conclude that, in hypoxic rats, altered pulmonary vascular function is largely independent of remodelling. Hence any drug that affects only remodelling is unlikely to restore pulmonary vascular function to normal and, like perindopril, may have only a modest effect on pulmonary artery pressure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Comparison of trough effect of telmisartan vs perindopril using self blood pressure measurement: EVERESTE study.

This multicentre study was aimed at comparing the trough effect of telmisartan and perindopril on diastolic blood pressure (DBP), using self blood pressure measurement (SBPM). A second objective was to compare the data obtained from SBPM with those provided by automatic office BP measurement. A total of 441 mild-to-moderate hypertensive patients were randomised to receive either telmisartan 40 mg or perindopril 4 mg for a period of 12 weeks. Patients whose clinic DBP remained higher than or equal to 90 mmHg at the end of the 6th week (W6) were given a double-dose regimen. Office BP and SBPM were performed at baseline (W0), at W6 and at week 12 (W12), both with the same automatic device. A greater diminution of trough DBP was obtained with telmisartan (-6.6+/-6.7 mmHg) than with perindopril (-5.1+/-7.0 mmHg; P=0.018). Regarding clinic BP, the same results were observed. Doubling dose was significantly less frequent with telmisartan (41%; n=85) than with perindopril (55%; n=115, P=0.005). Mean values of SBPM were lower than office BP values, with a difference of a greater importance at W0 than at W12: 6.6 vs 4.7 mmHg for systolic blood pressure (P<0.005) and 3.2 vs 1.4 mmHg for DBP (P<0.0001). At W12, isolated office hypertension was found in 9% of the patients (n=37), while there were 14% of the patients (n=55) with isolated home hypertension. In conclusion, the trough effect on DBP was statistically higher with telmisartan than with perindopril. SBPM values were lower than office BP values, with greater differences before than after treatment. About a quarter of the patients were found to be controlled with a method but not with the other one.

Adult↗
PubMed1994

An angiotensin converting enzyme inhibitor, perindopril, prevents progression of preformed atherosclerotic lesions in the cholesterol-fed rabbit.

1. The aim was to determine whether the angiotensin converting enzyme inhibitor perindopril, at a concentration approaching that used in human antihypertensive therapy, influences progression of preformed atherosclerotic plaques. 2. Rabbits had their right carotid artery deendothelialized with a balloon catheter, which resulted in the formation of a myointimal thickening. 3. At 14 weeks post surgery groups I, II and III (n = 6 per group) were fed a 1% cholesterol-enriched diet for 6 weeks, then group I rabbits were sacrificed. Groups II and III were placed on a normolipidaemic diet for a further 6 weeks with group III rabbits also receiving 0.3 mg day-1 kg-1 perindopril. Groups IV and V were treated the same as groups II and III, respectively, except that they received a normal diet throughout. 4. Group I rabbits fed a 1% cholesterol-enriched diet for 6 weeks developed lipid-filled lesions covering 26.3 +/- 14.3% of the surface area of the descending thoracic aorta. This was exacerbated in rabbits fed a 1% cholesterol diet for 6 weeks followed by 6 weeks on a normal diet (61.2 +/- 27.3%). In rabbits fed a 1% cholesterol diet for 6 weeks than a normal diet for a further 6 weeks plus 0.3 mg day-1 kg-1 perindopril, the percentage surface area covered by lesions was 21.8 +/- 15.8%. No lesions developed in the aortas of rabbits fed a normal diet. In the right coronary artery the resulting neointima in rabbits fed a 1% cholesterol diet for 6 weeks only was 42.4 +/- 5.7% of the cross-sectional area of the vessel wall, 57.4 +/- 8.0% in rabbits receiving 6 weeks' cholesterol diet than 6 weeks' normal diet, 36.0 +/- 6.6% in rabbits fed a 6-week cholesterol diet than 6 weeks' normal diet with 0.3 mg day-1 kg-1 perindopril and 33.2 +/- 4.9% and 31.8 +/- 3.1% in rabbits on a normal diet throughout with 0 and 0.3 mg day-1 kg-1 perindopril respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Further evidence that chronic perindopril treatment maintains neurohormonal suppression but does not lower blood pressure in chronic cardiac failure.

AIMS: Previous studies in heart failure (CHF) after temporary diuretic withdrawal have suggested that perindopril is associated with no first dose hypotension in comparison with other ACE inhibitors (ACEI) or placebo. The aim of this study was to explore further the profile of perindopril during chronic dosing. METHODS: We report the effects of acute and chronic (8 weeks) treatment with the ACE inhibitor perindopril (Per, 2-->4 mg daily) or placebo (P) in a double-blind parallel group study of 24 diuretic treated patients (17M; 67 +/- 8 years, 80 +/- 17 kg) with ischaemic cardiomyopathy (fractional shortening, 19 +/- 5%; radionuclide ejection fraction, 31 +/- 3%). Baseline biochemical, hormonal (ACE, Ang I, Ang II), isotopic renal function (GFR, ERPF, ECFV), pretreatment diuretic dose and heart failure scores were similar between groups. Concomitant cardiac treatments remained unchanged and diuretic withdrawal was not used to introduce treatment. RESULTS: There were no significant effects on electrolytes, liver function tests, serum or erythrocyte magnesium. There was no significant first dose fall in SBP over 6 h) (P, baseline 137 +/- 18; min 115 +/- 16 mmHg; Per, baseline 137 +/- 15; min 118 +/- 17 mmHg). Neither supine nor erect BP was significantly affected by chronic treatment (P, erect baseline 134 +/- 23/76 +/- 10 to 124 +/- 41/74 +/- 10 mmHg; Per, baseline 135 +/- 21/76 +/- 14 to 128 +/- 22/70 +/- 12 mmHg, P=NS). Active treatment was associated with significant ACE inhibition (P, baseline 47 +/- 17 to 43 +/- 17; Per baseline 49 +/- 15 to 14 +/- 7); aldosterone (P, baseline 337 +/- 179 to 375 +/- 306; Per, baseline 335 +/- 357 to 293 +/- 155 pg ml(-1)) and Ang II suppression (P, baseline 9 +/- 9 to 20 +/- 39; Per baseline 10 +/- 9 to 3 +/- 3 pM). Isotopic renal function was unaffected by either treatment. CONCLUSIONS: At this dose (2-4 mg orally) chronic perindopril therapy has no significant effect on blood pressure or renal function. Sustained neurohormonal suppression of ACE and AII occurred without evidence of AII reactivation. A lack of effect on BP at these doses may make perindopril suitable for study in unstable patients with acute HF or useful in those patients where there are concerns over ACEI induced hypotension.

Aged↗
PubMed1991

Acute and chronic effects of perindopril on tissue angiotensin converting enzyme activity.

The pattern of inhibition of tissue angiotensin converting enzyme (ACE) was studied in rats after acute and chronic (14 days) oral administration of perindopril. Free and total tissue ACE were measured by quantitative in vitro autoradiography using [125I]-351A as a radioligand and compared with plasma ACE and pressor responses to angiotensin I. Following oral perindopril, plasma perindoprilic acid and the pattern of inhibition of plasma ACE activity were maximal at 1 to 2 h, but recovered over 24 h. However, inhibition of the pressor response to angiotensin I was more prolonged, being 95% at 4 h, but had not fully recovered by 24 h. Acutely, ACE was markedly inhibited in renal proximal tubules, lung parenchyma, and aortic wall. At 24 h, ACE in these tissues had only partially recovered. Angiotensin converting enzyme in vascular endothelium of other organs showed a similar pattern of inhibition. In contrast, ACE in testicular seminiferous tubules was unaffected by perindopril. After chronic (14 days) administration of perindopril, total plasma ACE increased 3-fold, of which 49% was occupied by the inhibitor. Total tissue ACE in kidney and aorta did not change, and the pattern of inhibition observed acutely was maintained during chronic treatment. These results demonstrate a prolonged effect of ACE inhibitors on tissue ACE that may better explain the time course of these drugs than the changes in plasma ACE or plasma levels of the drugs.

Angiotensin I↗
PubMed2005

The effect of perindopril on cardiovascular morbidity and mortality in patients with diabetes in the EUROPA study: results from the PERSUADE substudy.

AIMS: The aim of this study was to assess the effect of the angiotensin converting enzyme inhibitor perindopril on cardiovascular events in diabetic patients with coronary artery disease. METHODS AND RESULTS: A total of 1502 diabetic patients with known coronary artery disease and without heart failure of 12 218 overall in the EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery (EUROPA) disease were randomized in a double-blinded manner to perindopril 8 mg once daily or placebo. Follow-up was for a median of 4.3 years. The primary end point was cardiovascular death, non-fatal myocardial infarction, and resuscitated cardiac arrest. Perindopril treatment was associated with a non-significant reduction in the primary endpoint in the diabetic population, 12.6 vs. 15.5%, relative risk reduction 19% [(95% CI, -7 to 38%), P=0.13]. This was of similar relative magnitude to the 20% risk reduction observed in the main EUROPA population. CONCLUSION: Perindopril tends to reduce major cardiovascular events in diabetic patients with coronary disease in addition to other preventive treatments and the trend towards reduction was of a similar relative magnitude to that observed the general population with coronary artery disease.

Adult↗
PubMed2000

Effect of the angiotensin-converting enzyme inhibitor perindopril on haemostasis in essential hypertension.

Endothelial damage, platelet hyperactivity and other changes of blood coagulation may play a role in the vascular complications of essential hypertension. Undesirable changes of haemostasis induced by some anti-hypertensive drugs can encourage the acceleration of atherogenesis. Therefore, the effect of angiotensin-converting enzyme (ACE)-inhibitors on haemostasis is of interest. The therapeutic dose of perindopril was previously shown to reduce platelet aggregation. In the present study, selected parameters of haemostasis were investigated in 23 patients with first and second stage of non-treated essential hypertension. The measurements were carried out before therapy, after 1 week of placebo administration, and after 1 week and after 1 month of ACE-inhibitor perindopril therapy in a once-daily dose of 4 mg. Plasma prothrombin time, activated partial thromboplastin time, fibrinogen level, plasminogen and antithrombin III activities, protein C and free protein S antigens, total fibrinolytic activity as well as fibrin monomers and D-dimers were assayed. There were no significant changes in any haemostasis variables investigated following placebo administration or perindopril therapy. On the basis of this study, no unfavourable effects on haemostasis induced by this therapy were found. The platelet-inhibitory effect of perindopril, without any harmful effects on coagulation or fibrinolytic activity and coagulation inhibitors, is desirable in the new approach to hypertension treatment. These properties of perindopril may be important in terms of the beneficial role of anti-hypertensive drugs in cardiovascular morbidity.

Adult↗