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 55 records · Page 3Linked to original sources
PubMed2005

Evidence for benefits of perindopril in hypertension and its complications.

Structural and functional changes in large and small arteries in hypertension, even at early stages, may affect one or several end organs such as the brain, heart, and kidneys, contributing to cardiovascular morbidity and mortality. Therefore, modern treatment strategies should not only target blood pressure (BP) reduction but also normalize vascular structure and function. The purpose of this article is to review the large body of evidence, from randomized double-blind clinical trials, that has been gathered in regard to the angiotensin-converting enzyme (ACE) inhibitor perindopril, demonstrating its efficacy in reducing BP, reversing abnormalities of vascular structure and function in patients with essential hypertension, and ultimately preventing cardiovascular events. At the site of small resistance arteries, long-term treatment with perindopril, but not atenolol, reduced arterial wall hypertrophy for a given BP reduction. The improvement in small artery function in response to structural changes is exemplified at the site of the coronary circulation. Perindopril increased coronary blood flow and coronary reserve, in parallel with the regression of periarteriolar and interstitial collagen of coronary arterioles. At the site of large arteries, long-term treatment with perindopril reduced carotid and radial artery wall hypertrophy, and reduced carotid artery internal diameter. In response to these structural changes, large artery function improved at the site of the carotid and brachial arteries, showing a higher arterial distensibility, and at the site of the coronary circulation, showing a normalized arterial dilation in response to a cold pressor test or an increase in blood flow. Moreover, in patients with end-stage renal disease, perindopril decreased pulse wave velocity independently of BP changes, resulting in a highly significant relative risk reduction in all-cause and cardiovascular mortality. The multifactorial antiatherosclerotic profile of perindopril suggests a beneficial effect not only in patients with uncomplicated hypertension but also in patients with established coronary heart disease or previous stroke, as exemplified by the EUropean trial on Reduction Of coronary events with Perindopril in stable coronary Artery disease (EUROPA) and the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS).

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

First LC-MS/MS electrospray ionization validated method for the quantification of perindopril and its metabolite perindoprilat in human plasma and its application to bioequivalence study.

A high throughput bioanalytical method based on solid phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS), has been developed for the estimation of perindopril and its metabolite perindoprilat, an angiotensin-converting enzyme inhibitor in human plasma. Ramipril was used as internal standard (IS). The extraction of perindopril, perindoprilat and ramipril from the plasma involved treatment with phosphoric acid followed by solid phase extraction (SPE) using hydrophilic lipophilic balance HLB cartridge. The SPE eluate without drying were analyzed by LC-MS/MS, equipped with turbo ion spray (TIS) source, operating in the negative ion and selective reaction monitoring (SRM) acquisition mode to quantify perindopril and perindoprilat in human plasma. The total chromatographic run time was 1.5 min with retention time for perindopril, perindoprilat and ramipril at 0.33, 0.35 and 0.30 min. The developed method was validated in human plasma matrix, with a sensitivity of 0.5 ng/ml (CV, 7.67%) for perindopril and 0.3 ng/ml (CV, 4.94%) for perindoprilat. This method was extensively validated for its accuracy, precision, recovery, stability studies and matrix effect especially because the pattern of elution of all the analytes appears as flow injection elution. Sample preparation by this method yielded extremely clean extracts with very good and consistent mean recoveries; 78.29% for perindopril, 76.32% for perindoprilat and 77.72% for IS. The response of the LC-MS/MS method for perindopril and perindoprilat was linear over the range 0.5-350.0 ng/ml for perindopril and 0.3-40 ng/ml for perindoprilat with correlation coefficient, r>/=0.9998 and 0.9996, respectively. The method was successfully applied for bioequivalence studies in human subjects samples with 4 mg immediate release (IR) formulations.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Safety profile of perindopril.

Approximately 25% of US adults have high blood pressure (BP). Selection of effective and safe antihypertensive therapy for these individuals is an important health-care priority. High BP can be treated with a wide range of antihypertensive agents from a number of different classes. These drugs may differ in their suitability for administration to different subpopulations of patients. Results from both clinical trials and postmarketing surveillance indicate that the angiotensin-converting enzyme (ACE) inhibitor perindopril erbumine is safe and well tolerated in a wide range of patients with hypertension. Cough, the most common ACE inhibitor-associated side effect, is also the most common clinical adverse event reported for perindopril, but <2% of perindopril-treated patients discontinue therapy because of cough. Other adverse events often associated with ACE inhibitors, first-dose hypotension and hyperkalemia, appear to occur less often with perindopril than with other agents in this class. The favorable safety profile for perindopril extends to a wide range of patients, including the elderly and those with either heart failure or renal disease. Perindopril has no negative effects on lipids in patients with hyperlipidemia or on glycemic control in patients with type 2 diabetes mellitus, and it reduces proteinuria in patients with renal disease. Perindopril has no known clinically significant drug-drug interactions. Thus, perindopril is a safe BP-lowering agent with documented tolerability in a wide range of patients with hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Comparison of perindopril versus captopril for treatment of acute myocardial infarction.

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality in patients with acute myocardial infarction (AMI), but these benefits might be limited by acute hemodynamic changes and difficulties in titrating to recommended doses. The objective of this study was to compare the hemodynamic changes and tolerability of perindopril with captopril after AMI. We randomized 212 patients to receive either captopril (n = 102) or perindopril (n = 110) within 72 hours of AMI. Captopril was given as an initial dose of 6.25 mg, and then 50 mg/day on day 1 and 100 mg/day thereafter. The corresponding doses of perindopril were 2, 4, and 8 mg/day. Acute hemodynamic changes, the percentage of patients who reached target doses, and in-hospital and 6-month cardiovascular events were monitored. Baseline clinical characteristics of the 2 groups were identical, but patients randomized to perindopril were in a higher Killip class (1.4 +/- 0.6 vs 1.2 +/- 0.5, p = 0.05). During the first 6 hours, treatment with perindopril resulted in higher minimal systolic (97 +/- 15 vs 91 +/- 14 mm Hg, p <0.01) and diastolic blood pressure (BP) (57 +/- 11 vs 54 +/- 10 mm Hg, p <0.02), later occurrence of minimal BP (3.6 +/- 0.2 vs 2.7 +/- 0.1 hour, p <0.001), and a lower incidence of persistent hypotension with systolic BP < 90 mm Hg for > or =1 hour (5% vs 16%; p < 0.01) compared with captopril. At initial administration, target doses of perindopril and captopril were attained in 97% and 82% of the patients, respectively (p < 0.01). After 6 months, there were no differences between patients treated with perindopril and captopril in mortality rates (6% vs 13%, p = 0.16) and need for revascularization (20% vs 21%, p = 0.9). Thus, in patients during AMI, perindopril treatment showed better short-term tolerance than treatment with captopril, with significantly less acute hemodynamic changes and fewer withdrawals.

Aged↗
PubMed2001

Long-term comparison between perindopril and nifedipine in normotensive patients with type 1 diabetes and microalbuminuria.

The aim of this study is to compare the efficacy of an angiotensin-converting enzyme inhibitor with a dihydropyridine calcium channel blocker in preventing progression to macroalbuminuria and/or a decline in renal function in normotensive patients with type 1 diabetes and microalbuminuria. Forty-two patients were randomized to treatment with either perindopril, slow-release nifedipine, or placebo. In the first 3 months, drug dosage was titrated to achieve a decrease in diastolic blood pressure of at least 5 mm HG: Thirty-three patients had a minimum of 24 months' data, and 25 patients were followed up beyond 36 months (mean, 67 +/- 4 months). Patients were studied every 3 months and at the end of the treatment period; those who remained normotensive discontinued therapy and were followed up for an additional 3 months. Baseline geometric mean albumin excretion rates (AERs) were as follows: perindopril, 66 microg/min; nifedipine, 59 microg/min; and placebo, 66 microg/min. During the first 3 years, 7 of the perindopril-treated but none of the placebo or nifedipine-treated patients reverted to normoalbuminuria (P < 0.01). Median AERs at 3 years of treatment in each group were 23 microg/min for perindopril, 122 microg/min for nifedipine, and 112 microg/min for placebo patients (P < 0.01). In patients with more than 3 years' follow-up, median AERs decreased by 45% in the first year and then stabilized in the perindopril group, but increased by 17.6% in the nifedipine group and 27.6% in the placebo group (P < 0.03) in the first year, then increased progressively. In these same patients, there was a significant decline in glomerular filtration rate in the nifedipine group (-7.8 +/- 1.8 mL/min/1.73 m(2)/y), but not in the other two groups (perindopril, -1.0 +/- 1.2 mL/min/1.73 m(2)/y; placebo, -1.3 +/- 1.1 mL/min/1.73 m(2)/y; P = 0.004). At the end of the study, cessation of treatment for 3 months was associated with a doubling of AERs in the perindopril-treated group, but no change in the other two groups (P < 0.001). In conclusion, long-term perindopril therapy is more effective than nifedipine or placebo in delaying the progression of diabetic nephropathy and reducing AER to the normoalbuminuric range (<20 microg/min) in normotensive patients with type 1 diabetes and microalbuminuria.

Adolescent↗
PubMed1994

Effectiveness of blood pressure control with once daily administration of enalapril and perindopril.

Ten patients who had their blood pressure controlled with enalapril (10 mg, n = 4; 20 mg, n = 6) and 10 control subjects on perindopril (4 mg, n = 6; 8 mg, n = 4) entered a double-blind crossover study. They received placebo or the active drug 1 week apart and had their blood pressure measured at 0, 2, 3, 4, and 24 h. Then they crossed over to the other angiotensin-converting enzyme inhibitors (4 mg perindopril congruent to 10 mg enalapril) and the double-blind study was repeated. Blood pressure control 2 to 4 h after drug administration was similar with both drugs (perindopril = 150 +/- 2/80 +/- 1; enalapril = 150 +/- 2/81 +/- 1). Twenty-four h after administration of perindopril blood pressure was lower than on enalapril (perindopril = 154 +/- 3/85 +/- 2; enalapril = 159 +/- 3/89 +/- 2). Enalapril, 2 to 4 h after administration, caused a greater decrease than placebo, whereas the change with perindopril did not differ from placebo. Twenty-four hours after receiving the active drug the blood pressure of subjects on perindopril did not differ from the peak effect when corrected for placebo and circadian variation, whereas the blood pressure on enalapril was higher. This study indicates that perindopril in the doses used has a longer duration of action than enalapril and is more suited to once daily use.

Aged↗
PubMed1992

Single-dose and steady-state pharmacokinetics and pharmacodynamics of perindopril in hypertensive subjects.

In a double-blind, placebo-controlled, parallel group study, 24 essential hypertensive subjects were randomised to receive either placebo or 2, 4, or 8 mg perindopril. Perindopril, its deesterified metabolite, perindoprilat, and perindoprilat glucuronide were separated with an ion-exchange resin and determined by a radioimmunoassay (RIA). Pharmacokinetic and pharmacodynamic parameters were estimated for 96 h after the first dose and after 4-week once-daily treatment. Perindopril peak levels were achieved in less than or equal to 2 h after dosing with an elimination t1/2 of 1-2 h. Peak levels of perindoprilat were achieved more slowly, reaching a maximum level 5-8 h after dosing, and had an elimination t1/2 of 40 h. Levels of the perindopril glucuronide peaked approximately 0.5 h later than perindopril, with an elimination t1/2 of approximately 2 h. Perindopril, perindoprilat, and its glucuronide conjugate followed linear kinetics in the dose range of 2-8 mg, and there was no evidence of accumulation with chronic dosing. Perindopril 4 and 8 mg produced significant decreases in predose blood pressure (BP) with chronic dosing, with maximal decreases occurring 5-7 h after dosing. Perindopril also produced a prolonged dose-dependent inhibition of plasma angiotensin-converting enzyme (ACE) activity that was maximum after 4 h and had not fully recovered by 48 h after a single dose.

Aged↗
PubMed1998

Perindopril effects on angiotensin I elimination in lung after experimental myocardial injury induced by intracoronary microembolization in rats.

The objective of the study was to determine whether angiotensin (Ang) I elimination in lung circulation depends on the degree of myocardial damage with and without early long-term perindopril treatment in a rat model of myocardial injury induced by intracoronary microembolization. Twenty-one days after surgery, steady-state arterial [125I]-Ang I and [125I]-Ang II blood concentrations were measured after high-performance liquid chromatography separation during i.v. infusion of [125I]-Ang I in three groups of male Wistar conscious rats: (a) sham-operated rats receiving saline (sham group, n = 6); (b) rats after coronary microembolization receiving saline (saline group, n = 7); and (c) rats after coronary microembolization receiving perindopril (2 mg/kg/day; from days 2-20 after embolization; perindopril group, n = 6). Ang I clearance and the Ang I-to-Ang II concentration ratio (R) were estimated. The embolization per se resulted in focal fibrosis, appearance of hypertrophic and dystrophic cardiac myocytes, and was accompanied by increased Ang I clearance (1,479 vs. 314 ml/min in sham group), 1.8-fold decreased [125I]-Ang II arterial level, and decreased R (0.5 vs. 1.2 in sham group; p < 0.05). Only Ang I concentrations and R were correlated with number of scars (r = -0.77; p < 0.05; and r = -0.82; p < 0.01, respectively). Captopril bolus (1 mg/kg, i.v.) caused similar reduction in [125I]-Ang II blood concentration in both sham and saline groups, but a significant increase of [125I]-Ang I blood concentration was detected in the sham group only. Thus in rats with coronary microembolization, a higher proportion of Ang I in lung circulation is eliminated by pathways independent of angiotensin-converting enzyme. In the perindopril group, a reduced number of scars (seven vs. 17 per slice in the saline group; p < 0.05), density of dystrophic and hypertrophic cardiac myocytes, and increased content of cell glycogen were observed. It was accompanied by normalized arterial [125I]-Ang I concentration, Ang I clearance, and R; [125I]-Ang II concentration tended to that in sham group. Only in the sham and perindopril groups was there significant correlation between Ang I and Ang II concentrations. The clear relation between number of scars per slice and R (r = -0.83; p < 0.01) was observed in all rats with embolized coronary vessels (saline and perindopril groups together). In conclusion, in this experimental, model Ang I elimination in the lung circulation was directly related to the degree of myocardial damage. Early perindopril treatment prevented maladaptive changes in Ang I processing and led to significant reduction of the undesirable aftereffects of myocardial tissue damage. Our data demonstrate the cardioprotective action of perindopril based on its beneficial influence on the renin-angiotensin system disturbances.

Angiotensin I↗
PubMedDate not supplied

Clinical experience with perindopril in patients nonresponsive to previous antihypertensive therapy: a large US community trial.

A subgroup analysis of a large US community trial was conducted to evaluate the antihypertensive efficacy and safety of perindopril, an angiotensin-converting enzyme inhibitor (ACEI), in 3159 patients who lacked blood pressure (BP) control at entry with previous antihypertensive therapy. Patients received 4 mg perindopril daily for 6 weeks. Based on physicians' assessment of BP response, the patients were then either maintained on 4 mg daily (group 1) or the dose was increased to 8 mg daily (group 2) for an additional 6 weeks. The mean baseline sitting BP was 158.2/92.9 mm Hg. Perindopril monotherapy produced a significant BP decrease from baseline of 11.6/6.5 mm Hg and 14.9/8.4 mm Hg at weeks 6 and 12, respectively. In group 1 patients, the majority of BP decrease occurred at week 6 (17.3/9.5 mm Hg) and was maintained until the end of week 12 (18.2/10.1 mm Hg). In group 2 patients, the BP decrease on the 4-mg dose was modest at week 6 by 5.2/3.1 mm Hg. However, further dose up-titration of perindopril to 8 mg resulted in a clinically significant BP decrease of 11.9/6.8 mm Hg from baseline to week 12. Significant antihypertensive effects of perindopril were also demonstrated in the special patient populations of elderly (>or=65 years), black, isolated systolic hypertension, patients with concomitant cardiovascular diseases, and patients nonresponsive to other ACEI therapy. Overall, BP control (<140/<90 mm Hg) was achieved in 40.0% of patients at week 12. Perindopril was well tolerated with cough and angioedema reported in 8.5% and 0.4% patients, respectively. Physicians assessed therapeutic response to perindopril as satisfactory in 73.8% patients who were nonresponsive to previous antihypertensive therapy. These results suggest that, in a community-based practice, perindopril monotherapy (4-8 mg/d) is an effective and safe therapeutic option in patients nonresponsive to previous antihypertensive therapy.

Aged↗
PubMed1992

The pharmacokinetics of perindopril in patients with liver cirrhosis.

Perindopril is a non-sulphydryl angiotensin converting enzyme (ACE) inhibitor which requires hydrolysis to its active metabolite, perindoprilat, to produce its effects. Ten cirrhotic patients with mild to severe disease were studied after oral administration of a single 8 mg dose of perindopril as its tert-butylamine salt. Compared with a historical control group of young healthy volunteers receiving the same single oral dose of perindopril, mean AUC values of the prodrug perindopril were double in patients with liver cirrhosis (602 +/- 294 s.d. ng ml-1 h vs 266 +/- 70 s.d. ng ml-1 h) whereas the mean AUC of perindoprilat was found to be similar (134 +/- 139 ng ml-1 h vs 120 +/- 29 ng ml-1 h). The partial metabolic clearance of perindopril to perindoprilat was much lower in the cirrhotics (26 +/- 12 ml min-1 vs 58 +/- 22 ml min-1). The maximum inhibition of plasma ACE activity measured in the cirrhotic patients (87.5 +/- 5.1%) was comparable with that previously reported with perindopril in patients with mild hepatic impairment as well as in patients with essential hypertension. We suggest that liver cirrhosis may be associated with imparied deesterification of perindopril to its active metabolite perindoprilat but that no dosage adjustment of perindopril is required in cirrhotic patients.

Adult↗
PubMed1996

Premedication with cyclosporine and perindopril modifies the ischaemia-reperfusion injury during liver resection in rats.

The aim of the present study was to determine whether pretreatment with cyclosporine (CsA), or perindopril (an angiotensin converting enzyme inhibitor) would modify the ischaemia-reperfusion injury of vascular occlusion during liver resection. Rats were allocated to four groups (n = 20 for each group): (i) sham operated; (ii) liver resection only; (iii) CsA (15 mg/kg); and (iv) perindopril (4 mg/kg during the three days before ischaemia-reperfusion injury with liver resection). The ischaemia was produced by a 30 min continuous occlusion. The model was designed to study liver function tests as the principal parameter. Compared with liver resection only, bilirubin was significantly lower with perindopril on days 8 and 23, but significantly higher with CsA on days 1 and 2. The alanine aminotransferase peak (day 1) was significantly lower with both perindopril and CsA. The prothrombin time was significantly less on days 2 and 4 with perindopril and day 4 with CsA. Liver histological changes were minimal in all groups at 30 min ischaemia, but were significantly less severe in the perindopril group. There was a significant decrease in the weight of the regenerated liver at day 23 with perindopril and a significantly lower drop in weight on day 1 and the rate of gain was significantly greater. Perindopril (4 mg/kg) and CsA (15 mg/kg) significantly alter liver function tests, liver histology and bodyweight following an ischaemia-reperfusion injury associated with liver resection. These findings could limit ischaemia-reperfusion injury for major liver resections in the clinical setting.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Long-term renoprotection by perindopril or nifedipine in non-hypertensive patients with Type 2 diabetes and microalbuminuria.

AIMS: To assess the efficacy of an angiotensin converting enzyme (ACE) inhibitor (perindopril), a dihydropyridine calcium channel blocker (sustained release nifedipine) and placebo in preventing the progression of albuminuria and decline in glomerular filtration rate (GFR) in patients with Type 2 diabetes and microalbuminaria. METHODS: A prospective, randomized, open, blinded end point study of 77 patients allocated to three treatment groups (23 perindopril, 27 nifedipine, 27 placebo). Drug doses were adjusted to achieve a decrease in diastolic blood pressure (DBP) of 5 mmHg in the first 3 months and additional therapy was given if hypertension developed (supine DBP > 90 mmHg and/or systolic blood pressure (SBP) > 140 mmHg if < or = 40 years; supine DBP > 90 mmHg and/or SBP > 160 mmHg if > 40 years). Median follow-up was 66 months, with 37 patients being followed for at least 6 years. RESULTS: Blood pressure remained within the non-hypertensive range in 83% of perindopril-, 95% of nifedipine- and 30% of placebo-treated patients (P < 0.01). In the first 12 months albumin excretion rate (AER) decreased by 47% only in the perindopril group (P = 0.04). From 12 to 72 months, AER gradients increased by 27% per year only in the placebo group (P < 0.01). After 6 years, macroalbuminuria had developed in 7/15 placebo compared with 2/11 in perindopril and 1/11 nifedipine-treated patients (P = 0.05). GFR did not change in the first 12 months, but thereafter the median GFR gradient (ml/min/1.73 m(2) per year) was -2.4 (P < 0.01) for perindopril-, -1.3 (P = 0.26) for nifedipine- and -4.2 (P = 0.01) for placebo-treated patients. The rate of decline in GFR for the study group as a whole from 12 months to the end of follow-up correlated negatively with mean arterial pressure (MAP) (r = -0.38, P < 0.01). During a 3-month treatment pause in 29 patients AER tended to increase only in the perindopril group (P < 0.07). CONCLUSIONS: Long-term control of blood pressure with perindopril or nifedipine stabilizes AER and attenuates GFR decline in proportion to MAP in non-hypertensive patients with Type 2 diabetes and microalbuminuria.

Adult↗
PubMed2004

Effect of perindopril on cerebral vasomotor reactivity in patients with lacunar infarction.

BACKGROUND AND PURPOSE: There is growing evidence that pharmacologic interference with the renin-angiotensin system may reduce risk of stroke, although the mechanism is unclear. Impaired reactivity of cerebral vessels has recently been recognized as a risk factor for stroke. We examined the effect of the angiotensin-converting enzyme (ACE) inhibitor perindopril on cerebral vasomotor reactivity to acetazolamide in patients with lacunar cerebral infarction. METHODS: We studied a cohort of male patients between 3 and 12 months after lacunar infarction confirmed on computed tomography. Each patient received perindopril 4 mg daily or matching placebo for 2 weeks in a randomized, double-blind, placebo-controlled crossover fashion. A 1-week washout period was observed between dosing periods. Cerebral vasomotor reactivity (increase in middle cerebral artery mean flow velocity in response to intravenous injection of 15 mg/kg acetazolamide) was measured before and after each dosing period using standard Doppler ultrasound techniques. RESULTS: Twelve patients (mean age 63.2+/-2.3 years) completed the protocol. There was no treatment order effect. Cerebral vasomotor reactivity was significantly greater after perindopril treatment (percent change from baseline +18.8+/-10.1% after perindopril, -4.6+/-4.1% after placebo; P=0.032). Dosing with perindopril did not affect resting cerebral blood flow velocity (percent change from baseline +3.1+/-9.5% after perindopril, -0.6+/-5.4% after placebo), nor was there a change in resting blood pressure (+1.8 mm Hg+/-3.1 after perindopril, +1.4 mm Hg+/-2.5 after placebo). CONCLUSIONS: This study provides evidence of a significant improvement in cerebral vasomotor reactivity induced by perindopril, beyond any effect on blood pressure. The results suggest a possible mechanism for the beneficial effect of ACE inhibition on stroke risk observed in recent clinical trials, and suggest a role for the renin-angiotensin axis in the pathophysiology of subcortical small vessel disease.

Acetazolamide↗
PubMed2005

Effect of the angiotensin-converting enzyme inhibitor perindopril on 24-hour blood pressure in patients with lacunar infarction: comparison between dippers and non-dippers.

Antihypertensive therapy based on the angiotensin-converting enzyme (ACE) inhibitor perindopril reduced the incidence of recurrent stroke in the Perindopril Protection against Recurrent Stroke Study (PROGRESS). The present study assessed the effect of perindopril on the 24-h blood pressure (BP) in hypertensive patients with lacunar infarction using ambulatory BP monitoring (ABPM). There was a 4-week observation period, a 4-week treatment period 1 (perindopril at 2 mg/day), and a 4-week treatment period 2 (perindopril at 4 mg/day). Twenty-seven hypertensive patients with lacunar infarction (10 dippers and 17 non-dippers) were enrolled. The average 24-h BP values were significantly decreased after both treatment periods. When the patients were divided into dippers and non-dippers, perindopril exhibited a different BP-lowering effect in the groups with these two circadian BP patterns. In dippers, daytime BP was significantly decreased, whereas nighttime BP was not, so an excessive fall of nighttime BP was not observed. In non-dippers, both daytime and nighttime BP were decreased, with a stronger BP-lowering effect at night. There was a significant inverse correlation between the magnitude of the change in nighttime BP and the night/day ratio. These results suggested that perindopril could induce a sustained decrease of the 24-h BP in patients with lacunar infarction. In particular, a more pronounced nighttime BP-lowering effect was observed in non-dippers. As the incidence of non-dippers is reported to be high among patients with cerebrovascular disease, better nighttime BP control by perindopril might have helped to improve the outcome of such patients in PROGRESS.

Aged↗
PubMed1991

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.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Interspecies comparison of the metabolic pathways of perindopril, a new angiotensin-converting enzyme (ACE) inhibitor.

1. The metabolism of perindopril (non-thiol angiotensin-converting enzyme inhibitor) was studied in rat, dog and monkey after single oral and i.v. administration of 14C-perindopril, and in man after a single oral dose. 2. Six biotransformation products of perindopril from urine, faecal and plasma samples (bile only for rats) were identified. 3. The main route of biotransformation in all species is the hydrolysis of the carboxylic ethyl ester side-chain, with the formation of perindoprilate, the active metabolite. 4. A minor route of biotransformation led to the acyl glucuronides of perindopril and perindoprilate. 5. Internal dehydration of perindopril and perindoprilate into cyclic lactam structures occurs. This route of metabolism is of minor importance except in humans.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Perindopril + indapamide: new preparation. Simple trick.

(1) The combination of perindopril 4 mg + indapamide 1.25 mg is approved for second-line treatment of hypertension after failure of perindopril alone. (2) The other combination, of a low dose of an angiotensin-converting-enzyme inhibitor (2 mg of perindopril) and a diuretic (0.625 mg of indapamide), is being promoted as first-line treatment of hypertension. (3) The clinical files for both preparations are limited to the strict minimum. (4) A dose-finding study showed that the perindopril 4 mg + indapamide 1.25 mg dose combination offered the best risk-benefit ratio by comparison with combinations containing the same perindopril dose but other indapamide doses. (5) A double-blind trial suggests that the antihypertensive activity of the perindopril 4 mg + indapamide 1.25 mg combination is equivalent to that of the captopril 50 mg + hydrochlorothiazide 25 mg and enalapril 20 mg + hydrochlorothiazide 12.5 mg combinations. The safety profile was the same for the three combinations. (6) The 2-mg perindopril combination has not been compared with perindopril monotherapy at the usual dose of 4 mg, or with indapamide monotherapy at a mean dose of 2.5 mg. (7) The two combinations are costlier than their competitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Assessment of antihypertensive efficacy of perindopril: results of double-blind multicenter studies versus reference drugs.

Perindopril (4 mg) was compared to atenolol (50 mg), captopril (25 mg b.i.d.), or a diuretic (hydrochlorothiazide 50 mg and amiloride 5 mg) in three studies involving a total of 503 hypertensive patients with diastolic blood pressure (DBP) of 95-125 mm Hg. A 4-week single-blind placebo period preceded 12 weeks of active treatment. Dose titration was at weeks 4 and 8 if the supine DBP was greater than 90 mm Hg. The dose was doubled and, if necessary, a diuretic was added in atenolol or captopril comparison and atenolol added in the diuretic study. The fall in supine blood pressure (BP) was 27/17 mm Hg with perindopril and 21/16 mm Hg for atenolol. Fifty-five percent on perindopril and 48% on atenolol were controlled on monotherapy, increasing to 78 and 58% with addition of hydrochlorothiazide. Captopril caused a BP fall of 19/12 mm Hg compared to 27/18 mm Hg for perindopril with 49% of both groups being controlled on monotherapy. Diuretic addition produced a greater antihypertensive effect with perindopril 75% compared to 57% of the captopril patients achieving control. Perindopril caused a comparable fall in supine BP to the diuretic combination 27/19 mm Hg and 31/18 mm Hg but the fall in erect systolic BP was significantly greater for the diuretic. At 3 months, 84% of the diuretic and 78% of the perindopril group achieved the target BP. There were no adverse effects on the blood count or blood chemistry with a low incidence of side effects and withdrawals from treatment. These studies show that perindopril compares favorably with the standard antihypertensive drugs.

Amiloride↗