J Chromatogr
Sci. 2005;43(2):73-75.
HPTLC Method for the Simultaneous Determination of Amlodipine
and Benazepril in Their Formulations.
Meyyanathan SN, Suresh B.
Department of Pharmaceutical Chemistry, J.S.S. College of Pharmacy
Ootacamund Eth 643 001, Tamilnadu, India.
A new, simple, precise, rapid, and selective high-performance thin-layer
chromatographic (HPTLC) method is developed for the simultaneous analysis
of amlodipine and benazepril in pharmaceutical formulations. The method
uses zolpidem as an internal standard (IS). The stationary phase used
is silica gel 60 F254 prewashed with methanol. The mobile phase consists
of an ethyl acetate-methanol-ammonia solution (8.5:2.0:1.0, v/v/v). Detection
and quantitation are performed densitometrically at l = 254 nm. The Rf
values of amlodipine, benazepril, and zolpidem (IS) are 0.58, 0.50, and
0.78, respectively. The limits of detection of amlodipine and benazepril
are 0.02 and 0.2 microg; linearity ranges are 0.1-0.8 and 0.2-2.0 microg;
and the percentage recoveries are 99.79% and 100.25%, respectively.
Ann Hum Biol. 2005 Jan-Feb;32(1):30-43.
A study of the relationships between angiotensin- converting enzyme
gene, chymase gene polymorphisms, pharmacological treatment with ACE inhibitor
and regression of left ventricular hypertrophy in essential hypertension
patients treated with benazepril.
He H, Li LM, Cao WH, Sun NL, Liu MZ, Hu YH.
Institute of Health Studies, School of Sociology and Population Studies,
59 Zhang Guan Cun Street, Beijing, 100872, China. hehong99@hotmail.com
BACKGROUND: About 15-37% of the adult population worldwide suffers from
hypertension. Hypertension is responsible for one-third of all global
deaths. Left ventricular hypertrophy (LVH) is one of the most important
characteristics of hypertension target organ damage and is also an independent
risk factor for cardiovascular events. Therefore, effective regression
of LVH is a main aim of hypertension treatment and also an important public
health concern. However, few studies of the regression of LVH have been
reported. In particular, little is known about the relationship between
the genotypes of angiotensin-converting enzyme (ACE) and chymase (CMA)
genes, and the effectiveness of antihypertensive drugs in regression of
LVH. AIM: The study investigated whether the insertion/deletion (I/D)
polymorphism of ACE gene and the A/B polymorphism of the CMA gene are
related to the regression of LVH in essential hypertension patients who
were participants in a long-term trial of therapy with benazepril. SUBJECTS
AND METHODS: Data from 157 patients was collected and used in the analysis.
The genotypes of ACE and CMA genes were identified by polymerase chain
reaction (PCR) and restriction fragment length polymorphism (RFLP). Left
ventricular mass (LVM) was measured by echocardiography, and left ventricular
mass index (LVMI) was calculated. RESULTS: Blood pressure was markedly
reduced and heart rate was unchanged by long-term treatment with benazepril.
Regression of LVH was observed. The mean reduction in LVMI was 41.50+/-28.48
g m-2. Reduction of LVM, LVMI and percentage reduction of LVMI were more
in the DD group than in the II and ID groups (P<0.05). No significant
difference in other indices was found in the different genotype groups
of ACE (P>0.05). No significant difference in all indices was found
among the different genotype groups of CMA (P>0.05). No interaction
was found between the genotypes of ACE and CMA. CONCLUSION: Hypertension
patients with the DD genotype are more likely to have regression of LVH
when treated with benazepril than patients with other genotypes of ACE.
No evidence was found to support an association between CMA genotype and
regression of LVH in patients or to support the interaction between the
two genes in regression of LVH.
J Hum Hypertens. 2005 Feb;19(2):139-44.
Rationale and design of a study comparing two fixed-dose combination
regimens to reduce albuminuria in patients with type II diabetes and hypertension.
Bakris GL, Toto RD, McCullough PA.
Department of Preventive and Internal Medicine, Rush University Medical
Center, Chicago, IL 60612, USA. George_L_Bakris@rush.edu
Diabetic nephropathy is the leading cause of end-stage renal disease
(ESRD). The early stage of nephropathy is manifested by the presence of
low levels of urinary albumin (microalbuminuria or urinary albumin excretion
>or=30 and <299 mg/day). Albuminuria is a marker for development
of nephropathy in type II diabetes and for increased cardiovascular morbidity
and mortality. Recent studies have demonstrated the importance of antihypertensive
agents that inhibit the renin-angiotensin-aldosterone (RAA) system to
reduce the risk and slow down the progression of renal disease. A new
clinical trial, GUARD (Gauging Albuminuria Reduction With Lotrel in Diabetic
Patients With Hypertension), is designed to compare the change in urinary
albumin to creatinine ratio after 1 year of initial treatment with either
amlodipine besylate/benazepril HCl or benazepril HCl/hydrochlorothiazide.
Other objectives include a comparison of the proportion of patients who
progress to overt diabetic nephropathy and the safety of these two combination
therapies in these high-risk patients.
J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Jan 25;814(2):303-8.
Simultaneous determination of benazepril hydrochloride and benazeprilat
in plasma by high-performance liquid chromatography/electrospray-mass
spectrometry.
Xiao W, Chen B, Yao S, Cheng Z.
Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research
(Hunan Normal University), Ministry of Education, Hunan Normal University,
Changsha 410081, PR China.
An analytical method for simultaneous determination of benazepril and
its active metabolite, benazeprilat, in human plasma by high-performance
liquid chromatography/electrospray-mass spectrometry was developed and
validated. Rutaecarpine was selected as the internal standard. The separation
was achieved on a C(18) column with acetonitrile and aqueous solution
(0.1% formic acid) as mobile phase with a gradient mode. The quantification
of target compounds was using a selective ionization recording at m/z
425.5 for benazepril, m/z 397.5 for benzeprilat and m/z 288.3 for rutaecarpine.
The correlation coefficients of the calibration curves were better than
0.992 (n = 6), in the range of 6.67-666.67 ng/ml for benazepril and benazeprilat.
The inter- and intra-day accuracy, precision, linear range had been investigated
in detail. The method can be used to assess the bioavailability and pharmacokinetics
of the drug.
J Huazhong Univ Sci Technolog Med Sci. 2004;24(3):254-8.
[Effects of the combined use of benazepril and valsartan on apoptosis
in the kidney of rats with adriamycin-induced nephritic glomerulosclerosis]
Han Z, Xing Y, Wang H, Liang X, Zhou J.
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong
University of Science and Technology, Wuhan 430030, China.
The effects of the combined use of angiotensin converting enzyme inhibitor (ACEI) benazepril and angiotensin II type 1 receptor antagonist (AT1RA) valsartan on apoptosis and the expression of apoptosis-related proteins Fas and FasL in the kidney of rats with adriamycin-induced nephritic glomerulosclerosis was investigated. Uninephrectomy and the injection of adriamycin induced the rat model of glomerulosclerosis. Benazepril (6 mg/kg), valsantan (20 mg/kg), or benazepril (3 mg/kg) plus valsantan (20 mg/kg) was respectively delivered daily by gavage to the rats in three treatment groups for 12 weeks. Apoptosis was examined by means of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL). Immunohistochemistry was adopted to detect the expression of Fas and FasL. Software of pathological analysis quantitated the levels of Fas and FasL. The results showed that as compared with those in the control group, the kidneys in the model group had more severe glomerulosclerosis, much more apoptotic cells and higher levels of expression of Fas and FasL. The degree of glomerulosclerosis, the number of apoptotic cells and the levels of expression of Fas and FasL were reduced by benazepril and valsartan. The combined use of benazepril and valsartan had the best therapeutic effect. It was concluded that benazepril and valsartan could suppress the excessive apoptosis of kidney cells by lowering the expression of the apoptosis-related proteins Fas and FasL, so as to postpone the process of glomerulosclerosis. The combined use of benazepril and valsartan has better therapeutic effect.
Am J Hypertens. 2004 Jul;17(7):590-6
Amlodipine/benazepril combination therapy for hypertensive patients
nonresponsive to benazepril monotherapy.
Chrysant SG, Bakris GL.
Oklahoma Cardiovascular and Hypertension Center and the University of
Oklahoma School of Medicine, Oklahoma City, Oklahoma 73132, USA.
BACKGROUND: Most patients with hypertension require two or more antihypertensive medications to achieve blood pressure (BP) goals. This double-blind study compared the efficacy and safety of high-dose combinations of amlodipine besylate (5 mg and 10 mg) and benazepril hydrochloride (40 mg) to benazepril hydrochloride (40 mg) alone in hypertensive patients not adequately controlled with benazepril hydrochloride (40 mg) monotherapy. METHODS: After a 2-week washout period and a 4-week lead-in period with benazepril 40 mg daily, patients with a mean sitting diastolic BP > or =95 mm Hg (i.e., nonresponders to benazepril 40 mg) were randomly assigned to active treatment with either a combination of amlodipine 5 mg and benazepril 40 mg for 4 weeks followed by a forced titration to amlodipine 10 mg and benazepril 40 mg for an additional 4 weeks, or to benazepril 40 mg alone for 8 weeks. RESULTS: The mean reduction in sitting BP from baseline (on benazepril) to endpoint (after 8 weeks of treatment) was 17/14 mm Hg with amlodipine/benazepril and 5/7 mm Hg with benazepril (P <.0001). The percentage of patients who met the diastolic BP response criteria (<90 mm Hg at endpoint or > or =10 mm Hg decrease from baseline) was 80% in the amlodipine/benazepril group and 45% in the benazepril group (P <.0001). The incidence of adverse events was infrequent and comparable for both treatment groups. CONCLUSION: High-dose amlodipine/benazepril combination therapy (5 mg/40 mg and 10 mg/40 mg) is an effective, safe, and well-tolerated treatment option for hypertensive patients who do not respond adequately to benazepril alone.
Zhonghua Yi Xue Za Zhi. 2004 Apr 2;84(7):592-5.
[Effect of different angiotensin converting enzyme inhibitors
on coronary collateral circulation]
[Article in Chinese]
Zhang XH, Ma XJ, Luo J, Shao JH, Geng QX, Zhu XL, Tang YS, Xu FY.
Department of Cardiology, Shandong Provincial Hospital, Jinan 250021,
China.
OBJECTIVE: To observe the effects of different angiotensin converting enzyme inhibitors (ACEI) on coronary collateral circulation. METHODS: Twenty-four healthy dogs underwent measurement of distolic aortic pressure (DAP) and ligation of the left anterior descending coronary artery. The distolic coronary pressure (DCP) and retrograde blood flow (Qret) were measured. Five days after the operation the dogs were randomly divided into three groups of 8 dogs: benazepril group (benazepril 10 mg qd); captopril group (captopril 12.5 mg bid) and control group (starch tablet was given). Thirty days after the operation a reflux catheter was inserted to measure the DCP and Qret again. Then the dogs were killed and their hearts were taken out to examine the pathologic changes. The angiotensin converting enzyme (ACE) activity levels in plasma and myocardium were examined by FAPGG spectrophotometry. RESULTS: (1) In the captopril group the plasma ACE activity was (24.1 +/- 0.6) U/L 10 days after medication, and 24.3 +/- 0.6 U/L twenty-five days after medication, both significantly lower than that before medication [(57.6 +/- 0.8) U/L, both P < 0.01]; in benazepril group the plasma ACE activity was (24.4 +/- 0.4) U/L ten days after medication, and (24.0 +/- 0.5) U/L 25 days after medication, both significantly lower than that before medication [(59.5 +/- 1.3) U/L, both P < 0.01]. The plasma ACE activity levels of captopril and benazepril groups, especially of the benazepril group, after medication were significantly lower than that of the control group. The tissue ACE activity levels of the captopril and benazepril groups were lower than that of the control group. (2) The values of DCP in the control and captopril group were higher after medication than before medication. A tendency of decrease of DCP was shown in the benazepril group, however, without statistical significance. (3) In the control group Qcol was (2.01 +/- 0.31) ml/min 25 days after medication, significantly than that before medication [(0.91 +/- 0.15) ml/min], the corresponding values in captopril group were (2.24 +/- 0.46) ml/min and (0.88 +/- 0.13) ml/min respectively in the captopril group and (3.18 +/- 0.27) ml/min and (0.89 +/- 0.11) ml/min respectively in the benazepril group with the value 25 days after in the benazepril group being the highest. (4) 30 days after operation collateral circulation was established in the ischemic myocardium in all 3 groups. The microvessel density in the ischemic zone of myocardium was higher than that in the nonischemic zone in all 3 groups. The microvessel density in the ischemic zone of myocardium was greater in the benazepril group than in the captopril and control groups. There was no difference in microvessel density between the captopril group and control group. CONCLUSION: Benazepril increases the microvessel density and collateral flow, promotes the creation of collateral circulation in ischemic area, but captopril has not such effects.
Clin Ther. 2003 Jun;25(6):1872-87.
Results of a pilot pharmacotherapy quality improvement program
using fixed-dose, combination amlodipine/benazepril antihypertensive therapy
in a long-term care setting.
Sapienza S, Sacco P, Floyd K, DiCesare J, Doan QD.
Christian Health Care Center, Wyckoff, New Jersey 07481, USA.
BACKGROUND: Hypertension is common in older adults (aged > or =65 years). Treatment frequently requires multiple medications and can be expensive. OBJECTIVE: This study measured the impact of substituting low-dose, fixed-combination therapy using the calcium channel blocker (CCB) amlodipine and the angiotensin-converting enzyme (ACE) inhibitor benazepril for high-dose CCB monotherapy or dual therapy with a CCB and an ACE inhibitor on antihypertensive drug costs, the incidence of adverse events, and blood-pressure control. METHODS: A multicenter, pilot pharmacotherapy quality improvement program was undertaken in a long-term care facility setting. Consultant pharmacists reviewed pharmacy records and medical charts from long-term care facilities, identifying older patients with a diagnosis of hypertension who either took CCB concomitantly with an ACE inhibitor or experienced adverse events on high-dose CCB therapy. Eligible patients were identified and their physicians contacted regarding switching them to fixed-dose combination therapy. RESULTS: A total of 51 patients at 17 facilities were switched to fixed-dose amlodipine/benazepril combination therapy; 94.1% were women and 5.9% were men (mean age, 85.1 years; range, 64-99 years). The mean number of comorbidities was 1.6. During the subsequent 2 months, mean blood pressure remained at levels similar to those at baseline. The number of patients reporting at least 1 drug-related adverse event decreased by 81.8% (P < 0.05), and the incidence of edema decreased by 75.0%. The mean per-patient cost of antihypertensive drugs decreased by 33.1% (P < 0.001), a mean per-patient savings of 19.21 US dollars per month. CONCLUSION: In patients aged > or =65 years with hypertension in long-term care facilities, a change from high-dose CCB monotherapy or CCB/ACE-inhibitor dual therapy to fixed-dose combination amlodipine/benazepril therapy significantly reduced drug costs and the incidence of adverse events and maintained blood-pressure control.
Eur J Clin Pharmacol. 2003 Aug;59(4):271-5.
Effect of benazepril amlodipine combination on fibrinolysis in
hypertensive diabetic patients.
Fogari R, Preti P, Lazzari P, Corradi L, Zoppi A, Fogari E, Mugellini
A.
Department of Internal Medicine and Therapeutics, Clinica Medica II, IRCCS
Policlinico San Matteo, University of Pavia, Piazza Golgi 2, 27100, Pavia,
Italy.
OBJECTIVE: The aim of this study was to compare the effects of benazepril and amlodipine in monotherapy versus in combination with plasma t-PA and PAI-1 activity in hypertensive type-2 diabetic patients. METHODS: After an initial 6-week wash-out, single-blind placebo period, 38 patients, 17 men and 21 females, were randomly assigned to receive benazepril 10 mg o.d. or amlodipine 5 mg o.d. or their combination o.d. at the same dosage for 6 weeks in three crossover periods each separated by a 2-week placebo wash-out period (3x3 latin square). At the end of the placebo run-in period and of each treatment period, BP, plasma PAI-1 and tPA activity were evaluated. RESULTS: Both benazepril and amlodipine were similarly effective in reducing systolic blood pressure (SBP) (-17.6 mmHg with benazepril and -19.8 mmHg with amlodipine; P<0.001 versus placebo), and diastolic blood pressure (DBP) (-11.1 mmHg, -13.2 mmHg, respectively). Combination therapy produced greater reduction in SBP/DBP values (-28.3/-20.5 mmHg; P<0.001 versus placebo, P<0.01 versus benazepril and amlodipine). Benazepril monotherapy significantly decreased plasma PAI-1 activity (-8.4 IU/ml, P<0.05) while it did not influence t-PA activity (+0.02 IU/ml). Amlodipine monotherapy produced a significant increase in t-PA activity (+0.27 IU/ml, P<0.05) while it did not influence PAI-1 activity (+0.8 IU/ml). The amlodipine/benazepril combination produced both a significant decrease in plasma PAI-1 activity (-8.7 IU, P<0.05) and a significant increase in t-PA activity (+0.26 IU/ml, P<0.05). CONCLUSIONS: These data suggest that in hypertensive type-2 diabetic patients, a population with an impaired fibrinolysis, the benazepril/amlodipine combination, may improve the fibrinolytic balance more than the single drugs.
J Hum Hypertens. 2003 Mar;17(3):207-12.
Effect of benazepril addition to amlodipine on ankle oedema and
subcutaneous tissue pressure in hypertensive patients.
Fogari R, Malamani GD, Zoppi A, Mugellini A, Rinaldi A, Vanasia
A, Preti P.
Dipartimento di Medicina Interna, Clinica Medica, IRCCS Policlinico S.
Matteo, Universita di Pavia, Pavia, Italy.
The aim of this study was to evaluate the effect of benazepril addition
to amlodipine antihypertensive treatment on ankle-foot volume (AFV) and
pretibial subcutaneous tissue pressure (PSTP), two objective measures
of ankle oedema. A total of 32 mild to moderate essential hypertensives
(DBP>90 and <110 mmHg), aged 30-70 years were studied. After a 4-week
placebo period, they were randomized to amlodipine 5 mg o.d. or benazepril
10 mg o.d. or amlodipine 5 mg plus benazepril 10 mg o.d. for 4 weeks,
according to a crossover design. At the end of the placebo period and
of each active treatment period, blood pressure,AFV and PSTP were evaluated.
AFV was measured using the principle of water displacement. PSTP was assessed
using a system, the subcutaneous pretibial interstitial environment with
a water manometer. Both amlodipine and benazepril monotherapy significantly
reduced SBP (-18.2+/-4 and -17.8+/-4 mmHg, respectively, P<0.01 vs
baseline) and DBP (-12.1+/-3 and -11.7+/-3 mmHg, respectively, P<0.01);
the reduction was increased by the combination (-24.2+/-5 mmHg for SBP,
P<0.001 and -16.8+/-4 mmHg for DBP, P<0.001). Amlodipine monotherapy
significantly increased both AFV (+17.1%, P<0.001 vs baseline) and
PSTP (+56.6%, P<0.001 vs baseline). As compared to amlodipine alone,
the combination produced a less pronounced increase in AFV (+5.5%, P<0.05
vs baseline and P<0.01 vs amlodipine) and PSTP (+20.5%, P<0.05 vs
baseline and P<0.01 vs amlodipine). Ankle oedema was clinically evident
in 11 patients with amlodipine monotherapy and in three patients with
the combination. These results suggest that ACE-inhibitors partially counteract
the microcirculatory changes responsible for Ca-antagonists-induced oedema
formation.
Int J Clin Pharmacol Ther. 2002 Jun;40(6):263-9.
Comparison of benazepril-amlodipine and captopril-thiazide combinations
in the management of mild-to-moderate hypertension.
Malacco E, Piazza S, Carretta R, Di Somma S, Mugellini A, Bertocchi
F, Palatini P; Italian Blood Pressure Study Group.
Third Division of Internal Medicine, Ospedale L. Sacco, University of
Milan, Italy.
OBJECTIVE: To compare the efficacy and tolerability of benazepril 10 mg + amlodipine 5 mg combination (BZ+AM) versus captopril 50 mg + hydrochlorothiazide 25 mg (CP+HT) combination. MATERIAL: 405 outpatients with mild-to-moderate arterial hypertension not adequately controlled by a monotherapy with ACE inhibitors or calcium channel blockers or diuretics entered this multicenter, double-blind, randomized, parallel-group study. METHOD: After a 2-week placebo run-in, 397 patients with sitting diastolic (D) blood pressure (BP) > 95 mmHg and/or sitting systolic (S) BP > 160 mmHg were randomized to receive either BZ+AM (201 patients) or CP+HT (196 patients) once daily for 12 weeks. Main outcome measure was sitting DBP and SBP values at the end of active treatment. The response rate was defined as the proportion of patients with either a final sitting DBP < 90 mmHg or decreased by at least 10 mmHg or a sitting SBP < 150 mmHg or decreased by at least 20 mmHg from baseline. RESULTS: The DBP and SBP values obtained with BZ+AM were, respectively, 2.7 and 3.7 mmHg lower than those obtained with CP+HT (both p < 0.001 vs. CP+HT). The response rate in the BZ+AM group (94.8%) was better than that observed in the CP+HT group (86.0%, p = 0.004). The incidence of adverse events was similar with the 2 treatment regimens (17.9% for both). CONCLUSIONS: These data suggest a higher antihypertensive efficacy of the fixed combination BZ 10 mg+AM 5 mg as compared with CP 50 mg+HT 25 mg.
Am J Hypertens. 2002 Jun;15(6):550-6.
Combination therapy of amlodipine/benazepril versus monotherapy
of amlodipine in a practice-based setting.
Messerli FH, Weir MR, Neutel JM.
Division of Research, Ochsner Clinic Foundation, New Orleans, Louisiana
70121, USA.
BACKGROUND: Community-based studies are conducted to determine the degree to which therapeutic interventions will succeed in real world settings. This large practice-based clinical trial assessed the efficacy and tolerability of fixed-dose combination therapy with amlodipine/benazepril, compared with amlodipine monotherapy, in patients with mild-to-moderate hypertension. METHODS: Hypertensive patients currently taking amlodipine were selected based on one of two criteria: inadequate blood pressure (BP) control on amlodipine (diastolic BP [DBP] > or = 90 mm Hg; group 1), or inability to tolerate amlodipine (DBP < or = 90 mm Hg, but with edema; group 2). Eligible patients were switched from 5 or 10 mg of amlodipine to 5/10 mg or 5/20 mg of amlodipine/benazepril for 4 weeks. In group 1 (n = 6410), primary efficacy outcome was change in mean sitting DBP. A secondary efficacy outcome was change in mean sitting systolic BP (SBP). In group 2 (n = 1502), primary efficacy outcome was the percentage of patients whose edema improved during therapy with amlodipine/benazepril when compared with amlodipine monotherapy. RESULTS: In group 1, mean sitting DBP declined from 96.5 mm Hg at baseline to 84.9 mm Hg at week 4, a mean reduction of 11.5 mm Hg (95% confidence interval [CI] -11.8 to -11.3 mm Hg; P < .001). From baseline to week 4, mean sitting SBP declined from 152.9 mm Hg to 137.3 mm Hg, a mean reduction of 15.6 mm Hg (95% CI -16.0 to -15.2 mm Hg; P < .001). In group 2, 85% (95% CI 83%-87%) experienced some improvement in edema compared with baseline levels. CONCLUSIONS: Fixed-dose combination antihypertensive agent amlodipine/benazepril was safe and effective for patients who experienced either inadequate BP control or edema with amlodipine monotherapy.
Zhonghua Liu Xing Bing Xue Za Zhi. 2000 Jun;21(3):190-3.
[Evaluation on the effect of Benazepril for hypertension through
postmarketing surveillance]
[Article in Chinese]
Cao W, Li L, Hu Y, Zhan S, Li X, Li P, Wu T, Li J, Wang T.
Department of Epidemiology, Beijing Medical University, Beijing 100083,
China.
OBJECTIVE: To evaluate the efficacy and safety of Benazepril used among the essential hypertensives. METHODS: 1 831 essential hypertensive patients aged 35 to 75 were randomly selected from a community and followed for 18 months. The level of blood pressure, status of taking Benazepril and side effects were sequencially collected. RESULTS: 1/3 of the patients had taken antihypertensive drug before the study and the rate of compliance was over 96%. The effective rate of Benazepril was 73.6% at three months and increased to 84.7% at 18 months. Comparing with the baseline data, SBP and DBP declined 10.8 mmHg and 6.7 mmHg respectively. The rate of side effect was 22.7%. Cough was most commonly seen among side effects. The peak of first recording on side effect occurred at three months including 60% of them mild. CONCLUSION: Results showed that Benazepril had good efficacy and safety for the essential hypertension patients in a long-term observation.
Pharmacoeconomics. 2002;20(1):37-47.
Antihypertensive treatment with and without benazepril in patients
with chronic renal insufficiency: a US economic evaluation.
Hogan TJ, Elliott WJ, Seto AH, Bakris GL.
MEDTECH, Morristown, New Jersey 07960, USA.
OBJECTIVE: To conduct an economic analysis in the US of antihypertensive treatment with and without benazepril in patients with chronic renal insufficiency. DESIGN: A four-state Markov model, using clinical data obtained from a 3-year randomised clinical trial [the Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency (AIPRI) study] plus its extension study (median 3.6 years), and cost data obtained from published US sources. The period of analysis was 7 years following randomisation. PERSPECTIVE: Healthcare payer. SETTING: Clinical data were obtained from multiple medical centres in three European countries as described in the published studies. Key economic data were obtained from the US Healthcare Financing Administration's End Stage Renal Disease programme. PATIENTS AND INTERVENTIONS: In the clinical studies on which this economic analysis was based, patients with chronic renal insufficiency of various aetiologies were randomised to antihypertensive therapy with or without concomitant benazepril. MAIN OUTCOME MEASURES AND RESULTS: Over 7 years of analysis, patients randomised to antihypertensive treatment with concomitant benazepril therapy incurred on average USD12991 (1999 values) lower medical costs than patients prescribed antihypertensive treatment without benazepril, and obtained an additional 0.091 quality-adjusted life years (QALYs). Costs and QALYs were greater for the benazepril arm than the placebo arm for all years of analysis after the first. Rank order stability of results favouring the benazepril therapy arm was found in sensitivity analyses of changes in key model parameters. Additional economic and health benefits favouring patients receiving benazepril would be seen if underlying model rates of dialysis and transplantation were increased, as may be appropriate to reflect treatment practice differences in the US relative to European countries. CONCLUSIONS: Benazepril therapy as a component of antihypertensive treatment of persons with chronic renal insufficiency initially costs money, but investment costs are recouped quickly and return on investment continues to grow. The impact of end-stage renal disease on patient health and healthcare costs is great. Thus, the quality-adjusted survival benefits and overall cost savings seen in benazepril recipients over a prolonged period (2 to 7 years) indicate that the strategy of prescribing benazepril to reduce progression of renal disease in patients with renal insufficiency is both clinically and economically beneficial compared with current antihypertensive regimens without ACE inhibition.
J Hypertens. 2001 Nov;19(11):2097-104.
Combination of hydrochlorothiazide or benazepril with valsartan
in hypertensive patients unresponsive to valsartan alone.
Waeber B, Aschwanden R, Sadecky L, Ferber P.
Division of Clinical Pathophysiology and Medical Teaching, University
Hospital, Lausanne, Switzerland.
OBJECTIVE : The aim of this open multicentric study was to investigate
the efficacy and safety of the addition of an angiotensin converting enzyme
(ACE) inhibitor (benazepril, 10 mg/day) or a diuretic (hydrochlorothiazide,
12.5 mg/day) for 4 weeks in patients with mild to moderate essential hypertension
having been treated for 4 weeks by an angiotensin II antagonist (valsartan,
80 mg/day) but still having a diastolic blood pressure (BP) > 90 mmHg
on this medication given alone. METHODS : A total of 327 patients were
included in the trial and 153 patients (46%) had their diastolic BP </=
90 mmHg after 4 weeks of valsartan monotherapy. These patients continued
the same treatment regimen for the next 4 weeks, but no further blood
pressure reduction was observed. The remaining patients were randomized
to either the valsartan-hydrochlorothiazide or the valsartan-benazepril
combination. RESULTS : The two combinations induced an additional significant
BP reduction, which was of similar magnitude for diastolic BP (-4.5 during
valsartan-hydrochlorothiazide treatment and -3.3 mmHg during valsartan-benazepril
treatment), but of greater magnitude for systolic BP during valsartan-hydrochlorothiazide
(-6.77 mmHg) than during valsartan-benazepril co-administration (-3.2
mmHg). At the end of the trial, the BP of the responders to the valsartan
monotherapy was lower than that of patients having required a combination
therapy. Valsartan given alone or in association with hydrochlorothiazide
or benazepril was well tolerated. CONCLUSION : These data therefore show
that in patients not responding sufficiently to angiotensin II receptor
blockade BP can be further and safely lowered by adding a small dose of
a diuretic or an ACE inhibitor, with the diuretic-containing combination
tending to being more effective in controlling systolic BP.
J Hum Hypertens. 2001 Jul;15(7):495-8.
Once-daily treatment of patients with hypertension: a placebo-controlled
study of amlodipine and benazepril vs amlodipine or benazepril alone.
Pool J, Kaihlanen P, Lewis G, Ginsberg D, Oparil S, Glazer R,
Messerli FH.
The Methodist Hospital, Houston, TX, USA.
OBJECTIVE: To compare the efficacy, tolerability, and safety of once-daily
therapy with amlodipine 5 mg/benazepril 10 mg vs amlodipine 5 mg, benazepril
10 mg, and placebo. DESIGN: Randomised, double-blind, placebo-controlled,
parallel-group, multicentre trial. SETTING: Twenty-two clinical centres,
including private practice groups and academic research clinics.Patients:
A total of 530 patients between 21 and 80 years of age with essential
hypertension were screened for the study, and 454 were randomised to treatment
with amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg, benazepril 10
mg, or placebo for 8 weeks. RESULTS: Amlodipine 5 mg/benazepril 10 mg
produced greater reductions from baseline in sitting diastolic blood pressure
than amlodipine 5 mg (P < 0.03), benazepril 10 mg (P < 0.001), and
placebo (P < 0.001). The response rate in the amlodipine 5-mg/benazepril
10-mg treatment group (66.4%) was better than that observed in the amlodipine
5-mg (50.0% P < 0.02), benazepril 10-mg (38.3% P < 0.001), and placebo
(24.4% P < 0.001) groups. There was no significant difference in heart
rate among the four groups. The incidence of oedema in the amlodipine
5-mg/benazepril 10-mg (1.7%) group was somewhat less than that in the
amlodipine 5-mg (4.5%) group. CONCLUSIONS: Therapy with amlodipine 5 mg/benazepril
10 mg was well tolerated and was superior to amlodipine 5 mg, benazepril
10 mg, and placebo in reducing sitting diastolic blood pressure in patients
with essential hypertension.
Expert Opin Pharmacother. 2001 Jan;2(1):165-78.
Amlodipine/benazepril: fixed dose combination therapy for hypertension.
Faulkner MA, Hilleman DE.
Creighton University School of Pharmacy and Allied Health Professions,
2500 California Plaza, Omaha, Nebraska 68178, USA.
Myocardial infarction, stroke, heart failure and end-stage renal disease
have all been linked to inadequate control of blood pressure. Despite
overwhelming evidence that uncontrolled hypertension is responsible for
a sizeable number of adverse health-related outcomes, control of the disease
remains considerably suboptimal. Available data demonstrate that in order
to achieve adequate blood pressure control, a large number of patients
require therapy with more than one medication. Fixed dose combination
antihypertensive therapy has many advantages over other treatment options.
Positive effects on blood pressure control, rates of adherence, adverse
effects and cost have been identified. Amlodipine/benazepril (Lotrel),
Novartis) is a fixed dose combination product indicated for the treatment
of hypertension. Although not currently recommended as first-line therapy,
studies confirm that this combination of a long-acting calcium antagonist
and an angiotensin-converting enzyme (ACE) inhibitor possesses substantial
blood pressure lowering capabilities. Whereas adverse events tend to become
more frequent with increasing doses of antihypertensive monotherapy, the
rate of adverse events attributed to amlodipine/benazepril in clinical
trials often correlates with rates ascribed to placebo. Amlodipine/benazepril
is capable of sustaining blood pressure control over a 24 h period and
appears to be minimally affected by an occasional dose omission. Unlike
the older calcium antagonists, amlodipine is unlikely to cause alterations
in myocardial contractility. Additionally, the amlodipine/benazepril combination
product costs less than the same therapy administered as the individual
components. It is, therefore, reasonable to consider therapy with amlodipine/benazepril
in appropriate patients after an adequate trial of antihypertensive monotherapy.
J Assoc Physicians India. 1998 Mar;46(3):283-5.
An open clinical trial of benazepril--a new ACE inhibitor in mild-moderate
hypertension.
Karnik ND, Oza YK, Sane SP, Kaushik R, Bhatt AD, Chawla KP, Vaidya
AB, Yajnik VH, Khokhani RC.
LTM Medical College and Hospital, Mumbai.
Benazepril hydrochloride, a new non-sulfhydryl ACE inhibitor (ACEI) was studied in a titrated dose of 10 mg-20 mg once a day for 6 weeks in 42 mild to moderate adult hypertensive patients with sitting diastolic blood pressure (SDBP) 95-114 mm Hg. The pre-drug SDBP(mean +/- SE) of 102.5 +/- 0.8 mm Hg showed a significant reduction to 87.5 +/- 0.93 mm Hg at the end of treatment. BP was controlled (SDBP < or = 90 mm Hg) in 34 (81%) patients and a drop of at least 10 mm Hg from the pre-treatment SDBP value was noted in 34 (81%) patients. Common adverse reaction was cough in 8(19%) patients. Clinically significant changes in laboratory evaluations were not seen in any patient. Study showed that benazepril in a dose range of 10 to 20 mg per day is an effective agent for treatment of mild to moderate hypertension.
