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PubMed1989

Tolerance and safety of perindopril.

Angiotensin converting enzyme inhibitors (ACEIs) constitute a safe and effective therapeutic class for the treatment of hypertension. However, they have been incriminated in the development of certain adverse effects, the most frequently reported being alteration in renal function, development of hypotension and cough. This justified the evaluation of renal function after short-term and long-term treatment with perindopril in hypertensive subjects. In patients with normal renal function, during short-term treatment (1 and 5 days), perindopril induced an increase in renal plasma flow without any modification of the glomerular filtration rate. During long-term administration (up to 18 months of treatment), no significant variation in plasma creatinine was observed. In elderly hypertensive patients or patients with chronic renal failure, the glomerular filtration rate was also preserved, apart from a few rare cases of decreased creatinine clearance, particularly after the addition of hydrochlorothiazide. A slight increase in plasma potassium, with no clinical significance, was observed when perindopril was used as single-agent therapy. Symptomatic hypotension was rarely reported with perindopril (0.2% of cases), even under conditions of salt and water depletion. Amongst the other adverse effects of ACEIs, cough, more recently identified, was investigated in detail. Its frequency was determined in a double-blind study comparing perindopril (1.2%) and captopril (2.4%). It was also evaluated in a long-term study in 632 hypertensive patients (391 treated for 1 year); its incidence was 2.9% and it was responsible for discontinuation of treatment in 8 cases. In this study, 36 patients stopped treatment prematurely because of an adverse effect (5.7%). No harmful drug interactions were reported. The combination of a thiazide diuretic potentiates the antihypertensive effect of perindopril and is perfectly tolerated. The favorable safety profile of perindopril should be related to the correct determination of effective doses.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Effect of perindopril on 24-hour blood pressure levels and hemodynamic responses to physical and mental stress in elderly hypertensive patients.

This study assessed the effects of an angiotensin-converting enzyme (ACE) inhibitor, perindopril, on the 24-hour blood pressure (BP) profile and hemodynamic responses to isometric exercise and mental stress in elderly hypertensive patients. We performed ambulatory BP monitorings and echocardiographic studies during hand-grip exercises and a mental stress test before and after the 10-week administration of perindopril in 11 elderly patients (mean age, 71.8 years). Office BP was significantly decreased by perindopril treatment. Both daytime and nighttime systolic BP decreased significantly without any change in circadian pattern (P < 0.05). Daytime diastolic BP was also significantly decreased by perindopril (P < 0.05); nighttime diastolic pressure was decreased, but this result was not statistically significant. The reduction in 24-hour BP was associated with a decreased left ventricular end-systolic dimension (P < 0.01) and an increased fractional shortening (P < 0.01), suggesting reduced afterload due to arterial dilatation. The left ventricular mass index was not changed by perindopril therapy, and neither were systolic and diastolic BP responses to the handgrip exercises. The increases in systolic BP during mental stress was augmented after perindopril therapy, although systolic BP during mental stress after treatment was significantly lower than before treatment (P < 0.05). These results indicate that perindopril is effective in reducing ambulatory 24-hour BP levels and is associated with improved systolic function caused by dilatation of resistance vessels.

Aged↗
PubMed1994

Clinical review of perindopril in the treatment of hypertension.

Perindopril is a long acting angiotensin-converting enzyme inhibitor with a perhydroindole group and no sulphydryl radical. Perindopril is a pro-drug that is hydrolyzed to the active metabolite perindoprilat. Perindopril is rapidly absorbed, reaching peak plasma concentrations about 1 h after a single oral dose. Its bioavailability is greater than 70% and is not influenced by meals. Perindoprilat reaches peak plasma concentrations 3 to 4 h after administration. The blood pressure lowering effect of perindopril has been shown in animal models with spontaneous and renovascular hypertension. In hypertensive patients dose response studies have shown a significant and linear relationship between the dose and the activity of perindopril. The antihypertensive efficacy of 4 and 8 mg doses is significantly greater than that of 2 mg or of placebo. The maximal response is attained about 4 to 6 h after the first dose. As demonstrated by 24 h blood pressure recordings in ambulatory patients, the antihypertensive activity of perindopril was still significant 24 h after the last dose. Clinical trials have indicated that perindopril is at least as effective as usual therapeutic doses of captopril, atenolol or a combination of hydrochlorothiazide plus amiloride in mild to moderate essential hypertension. Oral administration of 4 to 8 mg od significantly reduced supine and standing systolic and diastolic blood pressure, and adequate diastolic blood pressure control was attained in about 60 to 70% of patients with monotherapy. In the majority of patients, hypertension was controlled with a daily dose of 4 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed1993

Therapeutic safety of perindopril in the treatment of mild hypertension with concomitant nephropathy.

Angiotensin-converting enzyme (ACE) inhibitors are well established antihypertensives. Their effect on kidney function, however, seems to depend on the pathophysiological mechanisms underlying the clinical symptoms. In one part of the Perindopril and Therapeutic Safety Study (PUTS) the effect of a 6-week treatment with placebo or 4 mg/d of perindopril (Coversum, CAS 82834-16-0) on kidney function and albuminuria was investigated in 56 hypertensives with concomitant nephropathy. The study was performed as multicenter, randomized, placebo-controlled, double-blind study. The results show that perindopril reduced blood pressure effectively. The responder rate determined as a fall in blood pressure at least about 10 mmHg in the perindopril group was 39% vs. 21% in the placebo group. All investigated parameters of kidney function like serum creatinine, creatinine clearance, urinary excretion of albumin and alpha 1-microglobulin remained unchanged during the study. In a subgroup of patients with isolated albuminuria ACE inhibition reduced significantly the urinary albumin excretion (perindopril: -292 +/- 205 mg/g creat. vs. placebo: +61 +/- 48 mg/g creat: p < 0.05). From this study it can be concluded that in hypertension with concomitant nephropathy, except renovascular hypertension and hypertension in renal transplant recipients, ACE inhibition by perindopril will not impair kidney function. In the early phase of nephropathy with isolated albuminuria and normal serum creatinine perindopril improves albuminuria and seems to be even of benefit for the kidney.

Adult↗
PubMed1997

Antihypertensive effects of perindopril treatment in adult spontaneously hypertensive rats.

OBJECTIVE: To determine the effect of perindopril treatment and treatment withdrawal in the prevention of hypertension in adult male spontaneously hypertensive rats (SHR). ANIMALS AND METHODS: Beginning at 15 weeks of age, male SHR were treated with either distilled water (control) or different daily dosages of perindopril (1, 2 or 4 mg/kg) by gavage for 10 weeks, followed by 10 weeks of treatment withdrawal. Systolic blood pressure, heart rate and body weight of adult SHR were determined at regular intervals before, during and after the treatment withdrawal periods. At the end of the treatment withdrawal period, plasma and tissue samples were taken for measurement of noradrenaline levels. Angiotensin-converting enzyme (ACE) activity in the plasma from adult SHR and Wistar-kyoto (WKY) rats treated with perindopril 4 mg/kg for two weeks was measured by a radioassay method 6 and 24 h after treatment. RESULTS: Treatment with perindopril caused a dose-dependent lowering of blood pressure in SHR during the 10-week treatment. After withdrawal of the treatment, persistent lowering of blood pressure was found in SHR treated with higher dosages (2 or 4 mg/kg), but not in the 1 mg/kg group. There was no difference in the tissue level of noradrenaline among the control group and SHR previously treated with perindopril. In SHR and WKY treated with perindopril for two weeks, plasma level of ACE activity was reduced longer than 24 h compared with their respective controls. CONCLUSIONS: Chronic treatment of adult SHR with perindopril has a dose-dependent effect on the blood pressure of these animals both during and after withdrawal of treatment, but such a treatment had no long term effects on the noradrenaline levels in various tissues.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Persistent reduction in renal nerve growth factor mRNA after perindopril treatment of young spontaneously hypertensive rats.

Nerve growth factor (NGF) determines sympathetic innervation of target tissues, and NGF levels are increased in young spontaneously hypertensive rats (SHR). Angiotensin can affect NGF levels, and the persistent reduction in blood pressure after brief angiotensin-converting enzyme inhibition in young SHR may involve long-term changes in NGF and sympathetic innervation. We measured the relative abundance of renal NGF mRNA by reverse transcription-polymerase chain reaction in SHR during and after treatment from 6 to 10 weeks of age with vehicle, perindopril (3 mg/kg per day), the bradykinin B2 antagonist Hoe 140 (0.5 mg/kg per day), both perindopril and Hoe 140, or angiotensin II (Ang II; 200 ng/kg per minute). Glomerular filtration rates were estimated at 10 and 20 weeks of age. At 10 weeks of age, Ang II caused a significant (P<.01) increase and perindopril caused a significant (P<.01) decrease in renal NGF mRNA levels. Blockade of the bradykinin B2 receptor during perindopril treatment attenuated (P<.05) the reduction in NGF mRNA levels. Renal NGF mRNA (P=.005) and blood pressure (P<.001) remained significantly lower than control 10 weeks after perindopril treatment was stopped. The partial reduction in blood pressure at 20 weeks of age in rats that had received perindopril and Hoe 140 was not associated with any difference in renal NGF mRNA. Perindopril-induced long-term reduction in renal NGF mRNA levels may decrease sympathetic innervation and thereby contribute to the long-term posttreatment blood pressure reduction.

Aging↗
PubMed1993

Digoxin pharmacokinetics and perindopril in heart failure patients.

The influence of chronic perindopril treatment on digoxin pharmacokinetics was investigated in 10 patients with mild chronic heart failure under stable diuretic and digitalis treatment and normal renal function. Digoxin was administered at a dose of 0.125 mg/day (n = 2) or 0.250 mg/day (n = 8). The 24-hour steady-state digoxin profile was assessed before and after concomitant administration of perindopril for 1 month at doses of 2 mg once a day for the first 8 days and 4 mg once a day for the remaining 21 days. Chronic treatment with perindopril produced no significant effect on mean (+/- standard deviation) digoxin serum area under the curve for 24 hours (17.9 +/- 7.4 versus 16.3 +/- 4.4 ng/mL.h), peak digoxin concentration (1.3 +/- 0.54 versus 1.2 +/- 0.36 ng/mL), time to peak concentration (3 versus 4 hours), and apparent oral clearance of digoxin (237.7 +/- 109.6 versus 237.4 +/- 79.5 mL/min). Clinical and biologic tolerance of perindopril was good throughout the study. Chronic administration of perindopril did not alter steady-state digoxin kinetics in patients with mild chronic heart failure and normal renal function, indicating that no adaptation of the digoxin dose is required during co-prescription with perindopril in such patients.

Aged↗
PubMed1990

The effect of perindopril and hydrochlorothiazide alone and in combination on blood pressure and on the renin-angiotensin system in hypertensive subjects.

The pharmacodynamic effects and acceptability of perindopril (4 mg daily) and hydrochlorothiazide (25 mg daily) given alone or in combination for 1 month were investigated in a double-blind, placebo controlled, parallel group study. The pharmacokinetics of perindopril and its active metabolite perindoprilat and the time course of angiotensin converting enzyme inhibition were studied for 72 h following the last dose of treatment in the two appropriate groups. Similar decreases in blood pressure were seen 24 h after the last dose of perindopril or hydrochlorothiazide (11/7 mm Hg supine) given alone at these doses. The effect of these drugs given together was additive on diastolic blood pressure and synergistic on systolic blood pressure (24.5/12.6 mm Hg supine) taking into account the placebo response. The significant increase in plasma renin activity produced by perindopril alone was potentiated by concurrent administration of hydrochlorothiazide. The formation of perindoprilat was slightly reduced in the group also receiving hydrochlorothiazide and there was a very small reduction in ACE inhibition in this group. Perindopril, whether given alone or in combination with hydrochlorothiazide, was well tolerated and produced no clinically significant change in routine haematology or serum biochemistry. The additive or synergistic effects of perindopril and hydrochlorothiazide on blood pressure must be due to their complementary physiological actions and not to a pharmacokinetic interaction.

Adult↗
PubMed2005

Effects of perindopril on cardiac sympathetic nerve activity in patients with congestive heart failure: comparison with enalapril.

PURPOSE: The production of aldosterone in the heart is suppressed by the angiotensin-converting enzyme (ACE) inhibitor perindopril in patients with congestive heart failure (CHF). Moreover, perindopril has been reported to have more cardioprotective effects than enalapril. MATERIALS AND METHODS: Forty patients with CHF [left ventricular ejection fraction (LVEF) <45%; mean 33+/-7%] were randomly assigned to perindopril (2 mg/day; n = 20) or enalapril (5 mg/day; n = 20). All patients were also treated with diuretics. The delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS) and washout rate (WR) were determined from 123I-meta-iodobenzylguanidine (MIBG) images, and plasma brain natriuretic peptide (BNP) concentrations were measured before and 6 months after treatment. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and LVEF were also determined by echocardiography. RESULTS: After treatment, in patients receiving perindopril, TDS decreased from 39+/-10 to 34+/-9 (P < 0.01), H/M ratios increased from 1.62+/-0.27 to 1.76+/-0.29 (P < 0.01), WR decreased from 50+/-14% to 42+/-14% (P < 0.05) and plasma BNP concentrations decreased from 226+/-155 to 141+/-90 pg/ml (P < 0.0005). In addition, the LVEDV decreased from 180+/-30 to 161+/-30 ml (P < 0.05) and the LVESV decreased from 122+/-35 to 105+/-36 ml (P < 0.05). Although the LVEF tended to increase, the change was not statistically significant (from 33+/-8% to 36+/-12%; P = NS). On the other hand, there were no significant changes in these parameters in patients receiving enalapril. CONCLUSION: Plasma BNP concentrations, 123I-MIBG scintigraphic and echocardiographic parameters improved after 6 months of perindopril treatment. These findings indicate that perindopril treatment can ameliorate the cardiac sympathetic nerve activity and the left ventricular performance in patients with CHF.

3-Iodobenzylguanidine↗
PubMed1993

Efficacy and acceptability of perindopril in mild to moderate chronic congestive heart failure.

The aim of this 3-month double-blind, placebo-controlled, multicenter trial was to evaluate the clinical efficacy and safety of perindopril, a new long-acting angiotensin-converting enzyme inhibitor in the second-line treatment of mild to moderate chronic congestive heart failure. After a run-in period of at least 14 days, 125 patients with grade II or III New York Heart Association chronic congestive heart failure on baseline diuretic therapy were randomized to perindopril, 2 mg (n = 61), or placebo (n = 64), once daily. Assessment was at 2-week intervals for the first month and then monthly for the 2 following months. After 2 weeks, active treatment was increased to perindopril, 4 mg once daily, if systolic blood pressure was 100 mm Hg or greater. Apart from sex, the two groups were homogeneous before treatment. As shown by the end-point analysis, the increase in exercise time was greater with perindopril than with placebo for both the ergometric bicycle (+111 +/- 21 versus +16 +/- 20 seconds; p = 0.002) and the treadmill (+171 +/- 39 versus +36 +/- 42 seconds; p = 0.024). Compared with placebo, this increase in exercise tolerance with perindopril was accompanied by an improvement in New York Heart Association functional class (p = 0.009), overall heart failure severity score (p < 0.001), and cardiothoracic ratio (p = 0.05). Of the 12 withdrawals from the study, seven were attributed to adverse events, two in the perindopril group and five, including one death, in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Acute and long-term efficacy of perindopril in severe chronic congestive heart failure.

To assess the short- and long-term hemodynamic efficacy of perindopril, 15 patients (12 men and 3 women) diagnosed with congestive heart failure were treated with oral perindopril (4 mg daily) for 3 months in association with digitalis and diuretic maintenance therapy. Patients were in New York Heart Association (NYHA) functional classes III and IV. Underlying cardiopathy was ischemic (6 patients), hypertensive (5 patients), valvular (2 patients), and dilated cardiomyopathy (2 patients). Hemodynamics, angiotensin-converting enzyme (ACE) activity, and perindoprilat (the active metabolite of perindopril) blood titration were measured at 2 periods. Acute assessment was performed over 2 titration days on oral perindopril 2 mg (day 1) and 4 mg (day 2); measurements were performed at rest and at 0, 1, 4, 6, 8, 12, and 24 hours. Chronic assessment was performed after 3 months of treatment with oral perindopril, 4 mg daily. During the study, 1 patient withdrew due to low systolic blood pressure (< 100 mm Hg) and 3 severely impaired patients died due to a worsening of heart failure during the study. Among the 11 remaining patients, 6 were symptomatically improved. On 4 mg perindopril administration, hemodynamic improvement was similar for peak values at both day 2 and at 3 months. At day 2, compared with baseline, cardiac index increased by 21% (p < 0.05) and pulmonary capillary wedge pressure (PCWP) and mean arterial pressure (MAP) decreased by 54% and by 21%, respectively (p < 0.01). Similarly, at 3 months, cardiac index increased by 37% (p < 0.001) and PCWP and MAP decreased by 41% and 19%, respectively (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2004

Clinical experience with perindopril in African-American hypertensive patients: a large United States community trial.

BACKGROUND: The prevalence of hypertension is greater in African Americans, and management of this condition presents challenges for practicing physicians. METHODS: The effectiveness and safety of perindopril was evaluated in hypertensive African-American patients (n = 1412) and hypertensive white patients (n = 7745) who had participated in a large United States community trial. Patients received perindopril 4 mg once daily for 6 weeks. Based on physicians' clinical judgment at week 6, the dose was either maintained or increased to 8 mg for an additional 6 weeks. RESULTS: Reduction of blood pressure (BP) was significant with perindopril monotherapy (4 to 8 mg once daily) in African Americans and whites (P <.001). The magnitude of BP reduction was significantly more in whites (P <.001). Up-titration of perindopril achieved additional BP reduction in both ethnic groups (P <.001). Control of BP (<140/90 mm Hg) in elderly (>65 years of age) and diabetic African-Americans subgroups was achieved in 32.1% and 31.6%, respectively. Perindopril was safe and well tolerated. CONCLUSIONS: Perindopril monotherapy is effective and is a viable initial therapeutic option as an antihypertensive agent in African-American individuals with hypertension.

Aged↗
PubMed2005

Specific properties and effect of perindopril in controlling the renin-angiotensin system.

Perindopril is a long-acting, once-daily lipophilic angiotensin-converting enzyme inhibitor with high tissue angiotensin-converting enzyme affinity, lowering angiotensin II and potentiating bradykinin. Its efficacy, safety, and tolerability are well established in the treatment of hypertension and heart failure. Moreover, large morbidity-mortality trials, such as the EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) and Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS), have shown that antihypertensive treatment with perindopril reduces and prevents cardiovascular disease in a large range of patients with vascular diseases, whether or not they are hypertensive. Thus, the outcomes of these and other trials support the concept of cardiovascular protective properties of angiotensin-converting enzyme inhibition with perindopril in addition to the obvious blood-pressure-lowering effect. Considering its properties and the clinical evidence on efficacy and tolerability that has been gathered, perindopril fulfils the criteria of the latest guidelines for hypertension and cardiovascular disease management and should therefore be considered as a first-line antihypertensive agent, forming a consistent part of the comprehensive strategy against hypertension and related cardiovascular complications.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

ACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINENT.

OBJECTIVES: EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease [EUROPA] demonstrates reduction in cardiovascular mortality and myocardial infarction for a possible vascular and antiatherosclerotic effect of angiotensin-converting enzyme (ACE) inhibition with perindopril. Our objective was to study the effect of perindopril on endothelial function and to verify its link to risk and occurrence of cardiovascular events. METHODS: Blood from 1200 EUROPA patients was withdrawn at baseline and after 1 year of treatment with either perindopril or placebo to measure von Willebrand factor and from 45 healthy subjects and 87 EUROPA patients to study endothelial function at the cellular level by cultivating in vitro human umbilical vein endothelial cells. In this setting, we determined protein expression/activity of endothelial nitric oxide synthase and the rate of apoptosis. Plasma levels of angiotensin II, bradykinin, tumor necrosis factor alpha, and nitrite/nitrate were also measured. RESULTS: The occurrence of cardiovascular events was related to von Willebrand factor at baseline (P = 0.013) that also significantly decreased after 1 year's treatment (P < 0.001). Perindopril upregulated 19% and 27% protein expression/activity of endothelial nitric oxide synthase (P < 0.05) as well as reduced the rate of apoptosis by 31% (P < 0.05). There was also a significant reduction in levels of angiotensin II, increase in bradykinin, reduction in tumor necrosis factor alpha, and increase in nitrite/nitrate (P < 0.05 for all). CONCLUSIONS: Abnormal endothelial function occurs in patients with coronary artery disease, and this can be counteracted by angiotensin-converting enzyme inhibition with perindopril. These effects could contribute, at least in part, to explaining the results of the main EUROPA Study.

Aged↗
PubMed2001

Dosage considerations with perindopril for systemic hypertension.

Perindopril erbumine is a once-daily angiotensin-converting enzyme (ACE) inhibitor that effectively lowers systolic and diastolic blood pressure (BP) in patients with mild-to-moderate hypertension. Converted from the prodrug ester perindopril, the active diacid perindoprilat is distributed rapidly and extensively, primarily to tissues with high ACE activity. Its ability to lower BP is comparable to or better than that of other antihypertensive agents, both of its own class and other classes, and its trough-peak ratio is consistently between 75% and 100%, translating into 24 hours of true efficacy per dose. First-dose hypotension caused by an initial acute BP depression occurs less frequently with perindopril than with other ACE inhibitors, an advantage in volume-contracted patients and those whose BP is angiotensin II dependent, such as patients with congestive heart failure. A missed-dose study showed that most of the antihypertensive effect of perindopril remains for 24 to 48 hours after dosing, a characteristic that confers protection to patients who miss a dose. Perindopril improves the distensibility and compliance of large and small arteries, which are compromised in hypertension, and can effect vascular remodeling by a mechanism independent of BP lowering. The clinical implications of these effects are being investigated in large trials. Perindopril is well tolerated in the elderly, and combination therapy with a diuretic was shown to yield significant additional BP reduction. Perindoprilat is cleared renally; dosage should be adjusted in patients with renal impairment.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Effects of perindopril on cardiovascular remodeling.

The primary aim in the medical treatment of hypertension is to lower blood pressure (BP). A wide variety of agents have proved effective for meeting this goal. However, an ideal agent for management of hypertensive patients must also meet a number of additional criteria. It should have a significant positive impact on conditions that are likely to be associated with elevated BP and that are known risk factors for cardiovascular morbidity and mortality. This article reviews effects of the long-acting angiotensin-converting enzyme inhibitor perindopril erbumine on hypertension-associated blood vessel and myocardial remodeling known to be associated with increased cardiovascular risk. Long-term treatment with perindopril improves arterial compliance and increases the media-lumen ratio of peripheral resistance vessels. These effects appear to be at least partially independent of BP lowering. Reversal of hypertension-associated vascular remodeling with perindopril should decrease afterload and reduce or reverse left ventricular hypertrophy. Evaluation of patients who have received long-term perindopril therapy has shown this to be the case. This effect of perindopril on an important predictor of cardiovascular morbidity and mortality may also be partially independent of BP. The combination of treatment with such agents as perindopril and methods that permit early detection of vascular changes contributing to cardiovascular disease has the potential to markedly improve the prognosis for hypertensive patients and others at risk for development of cardiovascular disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Effects of perindopril on aldosterone production in the failing human heart.

The present study was designed to examine whether the production of aldosterone from the heart is suppressed by angiotensin-converting enzyme (ACE) inhibition in patients with heart failure. Forty-one patients with left ventricular systolic dysfunction were randomly divided into either the perindopril group (n = 21, perindopril 4 mg/day) or the placebo group (n = 20). Plasma levels of aldosterone and ACE activity were measured in the anterior interventricular vein, coronary sinus, and aortic root during cardiac catheterization. The levels of aldosterone as well as ACE activity were significantly higher at the anterior interventricular vein and the coronary sinus than at the aortic root in the placebo group (aldosterone: 92.1 +/- 9.0 vs 70.6 +/- 8.3 pg/ml [p <0.001]; 90.3 +/- 9.2 vs 70.6 +/- 8.3 pg/ml [p <0.001], respectively; ACE activity: 13.6 +/- 0.8 vs 12.2 +/- 0.7 IU/L [p <0.001], 13.4 +/- 0.8 vs 12.2 +/- 0.7 IU/L [p <0.001], respectively). On the other hand, there were no differences in the levels of aldosterone or ACE activity between the anterior interventricular vein and aortic root or between the coronary sinus and aortic root (aldosterone: 68.1 +/- 8.4 vs 69.9 +/- 9.4 pg/ml [p = NS]; 67.3 +/- 8.9 vs 69.9 +/- 9.4 pg/ml [p = NS], respectively; ACE activity: 9.7 +/- 0.8 vs 9.9 +/- 0.8 IU/L [p = NS]; 9.8 +/- 0.8 vs 9.9 +/- 0.8 IU/L, respectively) in the perindopril group. The levels of aldosterone as well as ACE activity were significantly lower at the anterior interventricular vein and coronary sinus in the perindopril group than in the placebo group. The difference in the level of aldosterone between the anterior interventricular vein and aortic root (Delta aldosterone [anterior interventricular vein - aortic root]) had a significant positive correlation with that of ACE activity (Delta ACE [anterior interventricular vein - aortic root]) (r = 0.536, p <0.001), whereas ACE activity in the aortic root had no significant correlation with either the aldosterone levels in the aortic root or Delta aldosterone (anterior interventricular vein - aortic root). Perindopril suppressed cardiac aldosterone production by mainly suppressing cardiac ACE activity in patients with heart failure. Thus, aldosterone production is activated in the failing ventricle and is suppressed by perindopril mainly via the suppression of cardiac ACE activity in patients with heart failure.

Aldosterone↗
PubMed2002

Losartan and perindopril effects on plasma plasminogen activator inhibitor-1 and fibrinogen in hypertensive type 2 diabetic patients.

BACKGROUND: This study compared the effects of losartan and perindopril on plasma plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in hypertensive type 2 diabetic patients. METHODS: We studied 85 nonsmoking outpatients, aged 46 to 64 years, with mild to moderate essential hypertension (diastolic blood pressure [BP] > 90 and < 110 mm Hg) and well controlled type 2 diabetes mellitus. After a 4-week washout placebo period, patients were randomized to received perindopril 4 mg once daily (n = 42) or losartan 50 mg once daily (n = 43) for 12 weeks according to a double-blind, parallel-group design. At the end of the placebo and active treatment periods, BP was measured and plasma PAI-1 and fibrinogen were evaluated. RESULTS: Both perindopril and losartan reduced systolic and diastolic BP values (-16/15 mm Hg and -15/14, respectively; P < .001 v placebo), with no difference between the two treatments. Plasma PAI-1 was reduced by perindopril (-10 ng/dL, P = .028 v placebo) but not by losartan (+4 ng/dL, NS), the difference between the two treatments being statistically significant (P < .01). Plasma fibrinogen showed no significant change with both drugs, although a decreasing trend was noted with perindopril. CONCLUSIONS: These findings indicate that perindopril but not losartan decreases PAI-1 in hypertensive type 2 diabetic patients, which suggests that the PAI-1 lowering effect is unrelated with AT, receptor blockade and could rather be due to the fact that the endothelial receptors that mediate PAI-1 expression in response to angiotensin II are not type 1 receptor subtypes. Different effects of the two drugs on the bradykinin system might also be implicated.

Angiotensin-Converting Enzyme Inhibitors↗