benazepril and Hypertension

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommended a thiazide-like diuretic, alone or in combination with other antihypertensive drug classes, as initial therapy for hypertension. JNC 7, however, did not specify preferred combinations. The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial was completed five years after the JNC 7 and demonstrated a 20 % advantage in cardiovascular risk reduction when blood pressure was lowered using the single-pill combination of benazepril-amlodipine compared to benazepril-hydrochlorothiazide (Jamerson et al. 359(23):2417-28 [1]). This new and significant finding provided compelling evidence that the long-standing preference for diuretics as initial therapy could be refuted, but it may also be relevant to the lower-than-expected reduction in coronary disease related events (compared to stroke) observed for decades prior to the ACCOMPLISH approach to therapy. The JNC 8 panel members recently published their recommendations, and while the group did not recommend benazepril-hydrochlorothiazide over other combinations, they did highlight the findings of ACCOMPLISH, rating the primary ACCOMPLISH paper as "good." The American Society of Hypertension position paper and the European Hypertension Society guidelines endorse such combinations as a first-line agent for patients with stage 2 hypertension. We review the current position of ACCOMPLISH in the guidelines regarding treatment of stage 2 hypertension.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Calcium Channel Blockers; Diuretics; Drug Combinations; Humans; Hydrochlorothiazide; Hypertension; Practice Guidelines as Topic; Randomized Controlled Trials as Topic

Cardiovascular (CV) disease, its associated risk factors and continued progression run in parallel with renal deterioration (cardio-renal syndrome). Most guidelines promote early treatment, including the use of ACE inhibitors to control CV risk in patients with chronic renal failure. The renoprotective effects of the ACE inhibitor, benazepril, independent of blood pressure control, have been demonstrated, as monotherapy or in combination with amlodipine or hydrochlorothiazide, in large clinical trials: Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) and Gauging Albuminuria Reduction with Lotrel in Diabetic Patients with Hypertension (GUARD) in patients with mild-to-severe chronic kidney disease. In the ACCOMPLISH trial, CV outcomes and renoprotective effects were greater in patients receiving benazepril in combination with amlodipine; the GUARD trial demonstrated that combined benazepril/hydrochlorothiazide was more effective than amlodipine combined with benazepril in reducing baseline urinary albumin:creatinine ratio and normalizing urinary albumin:creatinine ratio in patients with baseline microalbuminuria, although this effect was accompanied with a greater decrease in glomerular filtration rate than with benazepril/amlodipine. While this is not a study in patients with overt renal disease (patients had severe CV diseases), the ACCOMPLISH trial is the first large study to date to show the added benefit of combining ACE inhibitors and calcium-channel blockers in renal protection. Future large, well-controlled trials, designed to evaluate hard renal outcomes, are required to identify which patients will benefit most from particular combination treatment strategies in renoprotection.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Hypertension; Kidney Failure, Chronic; Risk Factors

Benazepril is a nonsulfhydryl ACE inhibitor with favorable pharmacodynamic and pharmacokinetic properties, well-established antihypertensive effects and a good tolerability profile. Recent clinical studies have demonstrated that patients treated with benazepril alone or in combination with hydrochlorothiazide or amlodipine may achieve beneficial renal outcomes that extend beyond blood pressure control. Furthermore, the recent Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed decreased cardiovascular morbidity and mortality with benazepril when administered as a cotreatment. An additional novel therapeutic area for benazepril is atrial fibrillation. Differences between combination therapies have implications for which patients may be best suited to particular interventions, and further studies are required to fully ascertain this potential.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atrial Fibrillation; Benzazepines; Calcium Channel Blockers; Diuretics; Drug Therapy, Combination; Humans; Hypertension; Kidney; Practice Guidelines as Topic; Prodrugs; Societies, Medical

In order to adequately control hypertension, the majority of patients will require treatment with more than one antihypertensive agent. Fixed-dose combination therapy offers several advantages, including improved efficacy, tolerability, and treatment compliance. Certain combinations have benefits in specific patient populations, such as the elderly or those with comorbidities. In this review, we evaluate the BP-lowering efficacy of olmesartan medoxomil/hydrochlorothiazide (HCTZ) and amlodipine besylate/benazepril in similarly designed, randomized, placebo-controlled studies in similar patient populations. This indirect comparison showed that both combinations significantly improve both systolic and diastolic BP compared with monotherapy with the individual agents or placebo; it also demonstrated that the combinations were well tolerated. Both combination therapies significantly improved response rates, but olmesartan medoxomil/HCTZ achieved the highest control rates compared with the individual agents. On the basis of an indirect comparison of published factorial design studies, olmesartan medoxomil/HCTZ appears to be at least as effective as amlodipine besylate/benazepril and may provide quantitatively greater reductions in diastolic BP at commonly used dosages. A randomized clinical trial comparing the two combinations is needed to confirm these findings.

Topics: Amlodipine; Antihypertensive Agents; Benzazepines; Blood Pressure; Drug Therapy, Combination; Factor Analysis, Statistical; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Olmesartan Medoxomil; Randomized Controlled Trials as Topic; Tetrazoles

When first introduced in 1981, angiotensin-converting enzyme (ACE) inhibitors were indicated only for treatment of refractory hypertension. Since then, they have been shown to reduce morbidity or mortality in congestive heart failure, myocardial infarction, diabetes mellitus, chronic renal insufficiency, and atherosclerotic cardiovascular disease. Pathologies underlying these conditions are, in part, attributable to the renin-angiotensin-aldosterone system. Angiotensin II contributes to endothelial dysfunction. altered renal hemodynamics, and vascular and cardiac hypertrophy. ACE inhibitors attenuate these effects. Clinical outcomes of ACE inhibition include decreases in myocardial infarction (fatal and nonfatal), reinfarction, angina, stroke, end-stage renal disease, and morbidity and mortality associated with heart failure. ACE inhibitors are generally well tolerated and have few contraindications. (Am Fam Physician 2002;66:473.)

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Captopril; Cardiovascular Diseases; Clinical Trials as Topic; Contraindications; Diabetic Nephropathies; Drug Costs; Enalapril; Fosinopril; Heart Failure; Humans; Hypertension; Indoles; Isoquinolines; Lisinopril; Meta-Analysis as Topic; Myocardial Infarction; Perindopril; Quinapril; Ramipril; Renin-Angiotensin System; Risk; Tetrahydroisoquinolines; United States

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.

Topics: Amlodipine; Antihypertensive Agents; Benzazepines; Blood Pressure; Clinical Trials as Topic; Drug Combinations; Humans; Hypertension; Treatment Outcome

Fixed-dose combination antihypertensive therapy has received interest since the publication of the JNC-VI report. Relatively few head-to-head comparative studies between fixed-dose combinations and first-line monotherapies for hypertension have been published. The objective of this study was to conduct a meta-analysis of various first-line monotherapies and the fixed-dose combination of amlodipine/benazepril. The results of the meta-analysis were used to compare the efficacy and safety of the first-line monotherapies with amlodipine/benazepril. The meta-analysis included 82 studies that included 110 treatment groups (cohorts). The study compared nine different monotherapies and one combination therapy (amlodipine/benazepril). Of the 82 studies, 22 were placebo-controlled and 60 were active treatment controlled. The mean absolute decrease in supine diastolic blood pressure (BP) ranged from 9.7 to 13.3 mm Hg with verapamil showing the greatest effect and captopril the least (13.3 +/- 3.0 mm Hg; 9.7 +/- 2.9 mm Hg, respectively). When studies were weighted by sample size, atenolol, verapamil, lisinopril and amlodipine/benazepril showed the greatest BP effect. When studies were weighted by variance, amlodipine/benazepril and atenolol showed the greatest BP effect. The percentage of patients controlled on therapy ranged from 54% to 79%. Lisinopril and amlodipine/benazepril showed the greatest percent controlled. The overall incidence of adverse effects ranged from 12.1% to 41.8% with lisinopril having the lowest and nifedipine having the highest incidence. The overall incidence of adverse effects resulting in drug discontinuance ranged from 1.3% to 10.7%, with amlodipine/benazepril having the lowest and nifedipine having the highest incidence. The results of the meta-analysis indicate that amlodipine/benazepril produces above average reductions in BP with a lower than average incidence of overall side effects and the lowest incidence of adverse effects resulting in drug discontinuance. The fixed-dose combination of amlodipine/benazepril achieves its goal of effective BP lowering with a minimum of significant side effects.

Topics: Amlodipine; Antihypertensive Agents; Benzazepines; Drug Combinations; Humans; Hypertension; Lisinopril; Treatment Outcome; Verapamil

Angiotensin converting enzyme inhibitors are effective in the treatment of hypertension and congestive heart failure. Within the past two years, four new agents in this class-benazepril, fosinopril, quinapril and ramipril--have been approved in the United States for use in the treatment of hypertension. These agents have been shown to be as effective as the older angiotensin converting enzyme inhibitors in treating hypertension and, in limited trials, congestive heart failure. The side effect profiles of the new agents are similar to those of other agents in this class that do not contain a sulfhydryl group. Fosinopril has a unique route of elimination that may make it the preferred agent in patients with renal failure. Otherwise, the new angiotensin converting enzyme inhibitors have no proven clinical advantages over other available agents. However, at moderate to high doses, the new agents may be substantially less expensive.

Topics: Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Fosinopril; Heart Failure; Humans; Hypertension; Isoquinolines; Quinapril; Ramipril; Tetrahydroisoquinolines

Benazepril is a nonsulfhydryl ACE inhibitor prodrug, which is converted in vivo to its active form, benazeprilat. Data from clinical studies have indicated that benazepril 5 to 80 mg (usually 10 to 20 mg), administered as a single daily dose, effectively decreases blood pressure in patients with mild to moderately severe hypertension. In a small number of comparative studies, the anti-hypertensive efficacy of benazepril appeared to be at least equivalent to that of captopril, enalapril, hydrochlorothiazide, nifedipine, nitrendipine or propranolol at usual therapeutic doses. Combinations of benazepril and hydrochlorothiazide or nifedipine achieved a greater lowering of blood pressure than benazepril alone, and this approach may be suitable for patients with more severe hypertension. Benazepril is reported to have beneficial effects on various indices of cardiac function and to improve clinical symptoms and exercise capacity in patients with congestive heart failure. The tolerability of benazepril in clinical trials has been very good, with an incidence of adverse effects similar to that observed in placebo recipients. Thus, benazepril appears to be an effective alternative to other members of its class for the management of hypertension, and further studies will accurately define its usefulness in congestive heart failure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Drug Evaluation; Heart Failure; Humans; Hypertension

The dose-response curve for benazepril, a new angiotensin-converting enzyme inhibitor, has been established from a systematic series of controlled clinical studies in patients with mild to moderate essential hypertension. The studies included a dose-ranging study, four dose-response studies (placebo-controlled or crossover), and four titration trials. The dose-response studies involved 803 patients and evaluated doses from 2 to 80 mg. Analysis of the data revealed the existence of a dose-response relationship over the dosage range of 10 to 80 mg given once daily. Efficacy of once-daily administration was shown by the persistence of significant blood pressure reduction over the 24-h dosing interval. In addition, the net trough-to-peak ratio (an indicator of net antihypertensive effect at the end of the dosing interval) was generally greater than 50%. The dose-determination studies with benazepril were conducted according to a well-designed strategy in which parameters were carefully defined. Based on these trials, the initial dosage for benazepril appears to be 10 mg once daily. Additional response may be observed at dosages up to 80 mg once daily.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Dose-Response Relationship, Drug; Humans; Hypertension; Time Factors

The safety and efficacy of benazepril, as monotherapy or as part of combination therapy with the diuretic hydrochlorothiazide, have been assessed in a number of studies, including comparative trials with the antihypertensive agents propranolol and nifedipine. These studies have included over 1300 patients with mild-to-moderate hypertension. Comparisons of the efficacy of benazepril and hydrochlorothiazide alone and in combination have shown that benazepril 20 mg once daily is as effective as or more effective in lowering diastolic blood pressure than hydrochlorothiazide 25 mg once daily and that the combination of benazepril 20 mg and hydrochlorothiazide 25 mg has a possibly synergistic effect on diastolic blood pressure. The results of comparative trials of benazepril with propranolol and nifedipine suggest that benazepril, administered alone or with the diuretic hydrochlorothiazide, is as effective as the other antihypertensive agents alone or in combination with hydrochlorothiazide. An additional study demonstrated that the combination of benazepril and nifedipine further lowered diastolic blood pressure in patients not responding to monotherapy with these agents. The safety of monotherapy with benazepril was found to be similar to that of the other antihypertensive agents. Safety of the combination of benazepril and hydrochlorothiazide was shown to be better than that of the combination of propranolol and hydrochlorothiazide. An attenuation of adverse experiences observed during nifedipine monotherapy was obtained when benazepril was added to the nifedipine regimen.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Drug Combinations; Humans; Hydrochlorothiazide; Hypertension

Data from clinical trials with benazepril suggest that the safety profile of benazepril is similar to that of other angiotensin-converting enzyme (ACE) inhibitors. Treatment-related side effects occurred in 20% of benazepril-treated patients and in 18% of patients receiving placebo. The most commonly reported side effects with benazepril were headache, dizziness, and fatigue. The incidence of side effects was not affected by the degree of hypertension, age, gender, race, dosage, or the degree of renal impairment. Side effects believed to be related to the pharmacologic action of ACE inhibitors as a class include symptomatic hypotension, which occurred at a relatively low rate with benazepril, and hyperkalemia and elevation of serum creatinine, which occurred to the same extent with benazepril as has been noted with other ACE inhibitors. The mechanism of cough as an ACE inhibitor side effect is unknown; the incidence was similar to that with other ACE inhibitors. Rash and taste disturbance have occurred rarely with benazepril. The incidence of neutropenia and of proteinuria was the same in both the benazepril and placebo groups. Renal failure in hypertensive patients treated with benazepril has not been reported. Overall, benazepril is generally well tolerated by hypertensive patients. The incidence of most side effects is comparable to that with other ACE inhibitors and placebo.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Drug Tolerance; Humans; Hypertension; Safety

Benazepril, a newer angiotensin-converting enzyme inhibitor, has been evaluated for the treatment of mild to moderate hypertension in patients 55 years of age and older. The results of the clinical trials conducted to date indicate that benazepril provides effective antihypertensive therapy in this population, with efficacy comparable to that demonstrated in younger patients. Benazepril does not produce precipitous decreases in diastolic blood pressure following the initial dose, and is well tolerated by the elderly. It has a safety profile similar to that of placebo and generally better than that of hydrochlorothiazide.

Topics: Aged; Aged, 80 and over; Aging; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Humans; Hypertension; Middle Aged

When a new drug is developed, one of the first requirements is to establish the correct dose. Unfortunately, in dose-determination studies, not enough lessons have been learned from the past. Pilot studies are often planned without sufficient statistical power, due to an insufficient number of patients and highly variable blood pressure measurements. In the development of the new angiotensin converting enzyme (ACE) inhibitor benazepril, crossover trials were used to obtain useful information. At the end of phase II of the benazepril development, a double-blind crossover study was carried out with 25 patients, and the results made it possible to redefine the 12- and 24-h effects of benazepril in comparison with placebo. Moreover, the crossover trial allowed an investigation of the biological effects of the treatment. In further work, the efficacy of 10 mg benazepril, administered once a day, was confirmed in comparison with captopril and enalapril, with a beta-risk of less than 20%. Since this crossover study yielded reliable data, and there was no carryover effect, a similar crossover design was used to study the interaction between benazepril and nifedipine. In the past, mistakes were made and many antihypertensive drugs were administered in high doses, with no further beneficial effect on blood pressure and an increased risk of side effects. Work described in this paper shows that fewer but better designed and implemented studies can improve the efficiency and value of dose-finding studies for antihypertensive drugs.

Topics: Antihypertensive Agents; Benzazepines; Blood Pressure; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Enalapril; Humans; Hypertension; Nifedipine

To investigate the effect of benazepril on plasma homocysteine (Hcy) levels and to analyze the correlation between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and changes in Hcy levels in response to benazepril.. A total of 231 patients with mild to moderate essential hypertension were enrolled, and benazepril was orally administered at a dose of 10 mg/d for 2 weeks. Plasma Hcy levels were measured by high-performance liquid chromatography at baseline and after 2 weeks of treatment. Genotyping of the MTHFR C677T polymorphism was performed by TaqMan probe technique.. There was no significant change in Hcy level after benazepril treatment for 2 weeks (P = .97). However, stratified by baseline Hcy levels, the patients with baseline Hcy <10 μmol/L had a significant increase in plasma Hcy levels (P = .003). The results from the multivariable linear regression analysis demonstrated a significant correlation between baseline Hcy levels and the changes in Hcy levels found in both the unadjusted (P = .002) and the adjusted model (P = .004). Strikingly, we found no significant effect modification by the MTHFR C677T polymorphism on the Hcy changes after benazepril treatment. There were also no statistically significant interactions of gene and environment factors (ie, gene smoking and drinking) on the changes in Hcy levels after benazepril treatment.. Benazepril may cause an increase in plasma Hcy levels among patients with hypertension with low baseline Hcy levels, while effect modification by MTHFR C677T genotypes on the changes in Hcy levels in response to benazepril was not significant among patients with essential hypertension.

Topics: Adult; Aged; Asian People; Benzazepines; China; Female; Homocysteine; Humans; Hypertension; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic

Angiotensin-converting enzyme 2 (ACE2), a newly discovered member of renin-angiotensin-aldosterone system, counterbalances the actions of angiotensin-converting enzyme. The objective of our study was to assess the association between rs2106809 polymorphism in ACE2 gene and the blood pressure response to ACE inhibitors in untreated hypertensive patients. After a 2-week, double-blind placebo run-in period, either benazepril or imidapril was administered for 6 weeks to 497 patients with mild to moderate essential hypertension. The achieved changes in BP were analyzed for their association with genotypes at ACE2 gene loci. In female hypertensive patients, the genotype frequency of ACE2 rs2106809 was 36.7%, 45.2% and 18.1% for CC, CT and TT genotypes, respectively. After 6 weeks of treatment, the reductions in diastolic blood pressure were significantly greater in female patients carrying the CC or CT genotype compared with those carrying the TT genotype (9.62±6.83 or 10.2±7.2 versus 6.81±6.31 mm Hg, respectively; P=0.045, analysis of variance (ANOVA)). Moreover, the reductions in mean arterial pressure were significantly greater in female patients carrying the CC or CT genotype compared with those carrying the TT genotype (12.1±7.5 or 12.0±7.9 versus 8.38±6.83 mm Hg, respectively; P=0.035, ANOVA). In male hypertensive patients, the genotype frequency of ACE2 rs2106809 was 58.1% and 41.9% for C and T genotypes, respectively. However, no association could be observed in males. We conclude that ACE2 rs2106809 is an important predictive factor of the response to antihypertensive treatment with ACE inhibitors in Chinese female hypertensive patients.

Topics: Adult; Aged; Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arterial Pressure; Asian People; Benzazepines; China; Double-Blind Method; Gene Frequency; Heterozygote; Homozygote; Humans; Hypertension; Imidazolidines; Middle Aged; Peptidyl-Dipeptidase A; Pharmacogenetics; Pharmacogenomic Variants; Phenotype; Polymorphism, Single Nucleotide; Precision Medicine; Prospective Studies; Renin-Angiotensin System; Sex Factors; Time Factors; Treatment Outcome

Pulse pressure (PP) is an independent risk factor for cardiovascular (CV) disease and death but few studies have investigated the effect of antihypertensive treatments in relation to PP levels before treatment. The Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial showed that the combination of benazepril+amlodipine (B+A) is superior to benazepril+hydrochlorothiazide (B+H) in reducing CV events. We aimed to investigate whether the treatment effects in the ACCOMPLISH trial were dependent on baseline PP. High-risk hypertensive patients (n=11,499) were randomized to double-blinded treatment with single-pill combinations of either B+A or B+H and followed for 36 months. Patients were divided into tertiles according to their baseline PP and events (CV mortality/myocardial infarction or stroke) were compared. Hazard ratios (HRs) for the treatment effect (B+A over B+H) were calculated in a Cox regression model with age, coronary artery disease, and diabetes mellitus as covariates and were compared across the tertiles. The event rate was increased in the high tertile of PP compared with the low tertile (7.2% vs 4.4% P<.01). In the high and medium PP tertiles, HRs were 0.75 (95% confidence interval [CI], 0.60-0.95; P=.018) and 0.74 (CI, 0.56-0.98, P=.034), respectively, in favor of B+A. There was no significant difference between the treatments in the low tertile and no significant differences in treatment effect when comparing the HRs between tertiles of PP. B+A has superior CV protection over B+H in high-risk hypertensive patients independent of baseline PP although the absolute treatment effect is enhanced in the higher tertiles of PP where event rates are higher.

Topics: Aged; Amlodipine; Antihypertensive Agents; Benzazepines; Blood Pressure; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Incidence; Male; Middle Aged; Myocardial Infarction; Retrospective Studies; Risk Factors; Stroke; Treatment Outcome

The purpose of this study was to compare the effects of benazepril and losartan on endothelial function and vascular stiffness, in patients with diabetes mellitus and hypertension.. We included hypertensive diabetic patients with an office systolic blood pressure (BP) ⩾ 130 mmHg and/or diastolic BP ⩾ 80 mmHg. Patients were rolled over to amlodipine for 6 weeks, then we performed C-reactive protein assays, BP measurement and vascular tests; next, patients were randomized to benazepril or losartan. The tests were repeated after 12 weeks.. We randomized 14 patients to benazepril and 16 to losartan. There were no differences in systolic (139 versus 134 mmHg, p = 0.618) and diastolic (82 versus 80 mmHg, p = 0.950) BP at the end of the study. C-reactive protein values were lower in the benazepril group (0.38 versus 0.42 mg/dl, p = 0.020). There was a slightly higher flow-mediated vasodilation (FMD) response in the benazepril group (45% increase, p = 0.057) than in the losartan group (19% increase, p = 0.132). Both central systolic BP (129 versus 123 mmHg, p = 0.934) and carotid-femoral pulse wave velocity (cfPWV) (8.5 versus 8.5 m/s, p = 0.280) were the same between groups.. Hypertensive diabetic patients using benazepril had a greater reduction in C-reactive protein, and a slight improvement in FMD, than those taking losartan.

Topics: Aorta; Benzazepines; Blood Pressure; C-Reactive Protein; Cohort Studies; Diabetes Mellitus, Type 2; Endothelium, Vascular; Female; Humans; Hypertension; Losartan; Male; Middle Aged; Pulse Wave Analysis; Vascular Stiffness

Studies suggest that statins have pleiotropic effects, such as reduction in blood pressure, and improvement in endothelial function and vascular stiffness.. To analyze if prior statin use influences the effect of renin-angiotensin-aldosterone system inhibitors on blood pressure, endothelial function, and vascular stiffness.. Patients with diabetes and hypertension with office systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 80 mmHg had their antihypertensive medications replaced by amlodipine during 6 weeks. They were then randomized to either benazepril or losartan for 12 additional weeks while continuing on amlodipine. Blood pressure (assessed with ambulatory blood pressure monitoring), endothelial function (brachial artery flow-mediated dilation), and vascular stiffness (pulse wave velocity) were evaluated before and after the combined treatment. In this study, a post hoc analysis was performed to compare patients who were or were not on statins (SU and NSU groups, respectively).. The SU group presented a greater reduction in the 24-hour systolic blood pressure (from 134 to 122 mmHg, p = 0.007), and in the brachial artery flow-mediated dilation (from 6.5 to 10.9%, p = 0.003) when compared with the NSU group (from 137 to 128 mmHg, p = 0.362, and from 7.5 to 8.3%, p = 0.820). There was no statistically significant difference in pulse wave velocity (SU group: from 9.95 to 9.90 m/s, p = 0.650; NSU group: from 10.65 to 11.05 m/s, p = 0.586).. Combined use of statins, amlodipine, and renin-angiotensin-aldosterone system inhibitors improves the antihypertensive response and endothelial function in patients with hypertension and diabetes.

Topics: Amino Acids; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Brachial Artery; Diabetes Mellitus, Type 2; Endothelium, Vascular; Female; Humans; Hypertension; Losartan; Male; Middle Aged; Pulse Wave Analysis; Renin-Angiotensin System; Statistics, Nonparametric; Time Factors; Treatment Outcome; Vascular Stiffness

This double-blind, double-dummy clinical trial evaluated the efficacy and safety of two strengths of fixed-dose combination of amlodipine/benazepril in Chinese hypertensive patients not adequately controlled with benazepril. Of 442 patients who received treatment with benazepril 10 mg for 4 weeks, 341 patients failed to achieve to diastolic blood pressure (DBP) <90 mmHg. These non-responders were randomized to receive amlodipine/benazepril 2.5/10 mg, or amlodipine/benazepril 5/10 mg, or benazepril 10 mg for 8 weeks. BP reductions with amodipinel/benazepril 2.5/10 mg (15.2/11.8 mmHg) or amlodipine/benazepril 5/10 mg (15.4/12.4 mmHg) were significantly greater than that with benazepril 10 mg (9.88/9.46 mmHg) at study end (p < 0.01, combination versus benazepril). BP control rate was 83.8% with amlodipine/benazepril 2.5/10 mg, 80.2% with amlodipine/benazepril 5/10 mg, 64.9% with benazepril 10 mg at study end (p < 0.01, combination versus benazepril). Three groups were generally well tolerated. Our study indicated that amlodipine/benazepril fixed-dose combination offered significant additional BP reductions and BP control rate compared with the continuation of benazepril monotherapy. No significant differences were observed in both BP reductions and BP control rate between amlodipine/benazepril 2.5/10 mg and amlodipine/benazepril 5/10 mg.

Topics: Adolescent; Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Calcium Channel Blockers; China; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Prevalence; Treatment Outcome; Young Adult

Combination therapy with benazepril 40 mg and amlodipine 10 mg (B+A) has been shown to be more effective than benazepril 40 mg and hydrochlorothiazide (HCTZ) 25 mg (B+H) in reducing cardiovascular (CV) events in high-risk patients with stage 2 hypertension with similar blood pressure reductions. In the present post hoc analysis, we evaluated whether B+A is more effective than B+H for reducing CV events in patients with known coronary artery disease (CAD) at baseline in a subgroup analysis of the Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) study. The main trial randomized 11,506 patients. Of those, 5,744 received B+A and 5,762 received B+H. Of the 11,506 patients, 5,314 (46%) were classified as having CAD at baseline. The mean patient follow-up period was 35.7 months for the B+A group and 35.6 months for the B+H group. The primary end point was the interval to the first event of composite CV morbidity and mortality. At baseline, significant differences were present between the 5,314 with CAD and the 6,192 without CAD. The patients with CAD had a lower systolic blood pressure and heart rate, a lower incidence of diabetes, and greater incidence of dyslipidemia. However, no baseline differences were found between the randomized B+A and B+H groups. In the patients with CAD, an 18% reduction occurred in the hazard ratio for CV events (primary end point) with B+A versus B+H (p = 0.0016). In a prespecified secondary analysis of the composite end point, including only CV death, myocardial infarction, and stroke, the hazard ratio in the patients with CAD was reduced by 25% (p = 0.0033) in the B+A group compared with the B+H group. B+A was more effective than B+H at comparable blood pressure reductions for reducing CV events in patients, regardless of the presence of CAD. In conclusion, our findings suggest that the combination of B+A should be preferentially used for older patients with high-risk, stage 2 hypertension.

Topics: Aged; Amlodipine; Antihypertensive Agents; Benzazepines; Coronary Artery Disease; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Prospective Studies; Risk Assessment

Combination therapy is an effective method to reduce the blood pressure (BP) for patients with hypertension. This study was performed to evaluate the efficacy and safety of benazepril/lercanidipine compared with benazepril alone in patients with mild-to-moderate hypertension.. One hundred and eighty-one patients with mild-to-moderate primary hypertension were assigned in this randomized, single-blind, parallel-group study and were randomly divided into group A (benazepril 10 mg/lercanidipine 10 mg) and group B (benazepril 10 mg) for 8 weeks. At 4 weeks, the dosage of Benazepril was titrated up to 20 mg if the diastolic blood pressure (DBP) remained ≥ 90 mmHg. BP control and side effects were evaluated at the end of 1, 4 and 8 weeks.. The baseline characteristics of the two groups were similar. The BP in both groups decreased from the baseline (P < 0.05). At the end of 4 and 8 weeks, Benazepril/Lercanidipine produced greater BP reduction than Benazepril alone (P < 0.05). The comparison of the rate of BP control for the benazepril/lercanidipine and benazepril groups at the end of 1, 4, and 8 weeks were 41.2% vs. 37.6% (P > 0.05), 67.1% vs. 44.7% (P < 0.05), and 71.8% vs. 45.9% (P < 0.05). There was no significant difference of side effects between the two groups.. The benazepril/lercanidipine combination is more effective in reducing BP than benazepril alone, while it does not increase the incidence of side effects.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Single-Blind Method

In previous clinical trials in high-risk hypertensive patients, paradoxically higher cardiovascular event rates have been reported in patients of normal weight compared with obese individuals. As a prespecified analysis of the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, we aimed to investigate whether the type of hypertension treatment affects patients' cardiovascular outcomes according to their body size.. On the basis of body-mass index (BMI), we divided the full ACCOMPLISH cohort into obese (BMI ≥30, n=5709), overweight (≥25 to <30, n=4157), or normal weight (<25, n=1616) categories. The ACCOMPLISH cohort had already been randomised to treatment with single-pill combinations of either benazepril and hydrochlorothiazide or benazepril and amlodipine. We compared event rates (adjusted for age, sex, diabetes, previous cardiovascular events, stroke, or chronic kidney disease) for the primary endpoint of cardiovascular death or non-fatal myocardial infarction or stroke. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00170950.. In patients allocated benazepril and hydrochlorothiazide, the primary endpoint (per 1000 patient-years) was 30·7 in normal weight, 21·9 in overweight, and 18·2 in obese patients (overall p=0·0034). However, in those allocated benazepril and amlodipine, the primary endpoint did not differ between the three BMI groups (18·2, 16·9, and 16·5, respectively; overall p=0·9721). In obese individuals, primary event rates were similar with both benazepril and hydrochlorothiazide and benazepril and amlodipine, but rates were significantly lower with benazepril and amlodipine in overweight patients (hazard ratio 0·76, 95% CI 0·59-0·94; p=0·0369) and those of normal weight (0·57, 0·39-0·84; p=0·0037).. Hypertension in normal weight and obese patients might be mediated by different mechanisms. Thiazide-based treatment gives less cardiovascular protection in normal weight than obese patients, but amlodipine-based therapy is equally effective across BMI subgroups and thus offers superior cardiovascular protection in non-obese hypertension.. Novartis Pharmaceuticals.

Topics: Aged; Amlodipine; Antihypertensive Agents; Benzazepines; Body Mass Index; Body Size; Body Weight; Cardiovascular Diseases; Double-Blind Method; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Obesity

The ACCOMPLISH Trial investigated intensive antihypertensive combination treatment with benazepril + amlodipine (B+A) or benazepril + hydrochlorothiazide (B+H) on cardiovascular outcomes in patients with systolic hypertension. We analyzed the baseline predictors of achieving a systolic blood pressure (SBP) <140 mmHg and achieved SBP level by the end of 12 months in both treatment groups.. Baseline and 12-month SBP was available in 10,506 patients, of whom 6250 had diabetes. Univariate and multivariate logistic regression models were used for SBP control at 12 months and multivariable regression models were used for the prediction of SBP at 12 months. A stepwise procedure was used to select significant (p < 0.001) predictors in multivariate analyses.. Mean (± SD) BP fell from 145.4/80.1 (± 18.3/10.7) mmHg at randomization to 132.8/74.7 (± 16.0/9.6) mmHg at 12 months. The main baseline predictors of SBP control <140 mmHg were region (USA >Nordic region) and Caucasian ethnicity in both randomization arms. A higher diastolic BP and the use of lipid lowering agents indicated favorable effects in the B+H arm only. The predictors of uncontrolled SBP were: (i) higher baseline SBP values, (ii) higher number of previous antihypertensive medications in both arms, (iii) the previous use of insulin in the B+A arm, and (iv) pre-trial calcium channel blocker (CCB) use in the B+H arm. Additionally, pre-trial use of thiazides and electrocardiogram (ECG)-left ventricular hypertrophy (LVH) at baseline predicted higher, and smoking lower absolute SBP in the B+A arm and the use of thiazides and proteinuria a higher SBP in the B+H arm.. Irrespective of treatment, patients in the USA and Caucasians achieved better SBP control, whereas higher baseline SBP and more previous antihypertensive medications indicated less control. Concomitant use of lipid lowering treatment indicated a better SBP control in the benazepril + hydrochlorothiazide arm. Lastly, insulin use and ECG-LVH in the benazepril + amlodipine arm and proteinuria in the benazepril + hydrochlorothiazide arm indicated poor control.

Topics: Amlodipine; Antihypertensive Agents; Benzazepines; Drug Therapy, Combination; Electrocardiography; Female; Humans; Hydrochlorothiazide; Hypertension; Logistic Models; Male; Systole

The ACCOMPLISH trial (Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension) was a 3-year multicenter, event-driven trial involving patients with high cardiovascular risk who were randomized in a double-blinded manner to benazepril plus either hydrochlorothiazide or amlodipine and titrated in parallel to reach recommended blood pressure goals. Of the 8125 participants in the United States, 1414 were of self-described Black ethnicity. The composite kidney disease end point, defined as a doubling in serum creatinine, end-stage renal disease, or death was not different between Black and non-Black patients, although the Blacks were significantly more likely to develop a greater than 50% increase in serum creatinine to a level above 2.6 mg/dl. We found important early differences in the estimated glomerular filtration rate (eGFR) due to acute hemodynamic effects, indicating that benazepril plus amlodipine was more effective in stabilizing eGFR compared to benazepril plus hydrochlorothiazide in non-Blacks. There was no difference in the mean eGFR loss in Blacks between therapies. Thus, benazepril coupled to amlodipine was a more effective antihypertensive treatment than when coupled to hydrochlorothiazide in non-Black patients to reduced kidney disease progression. Blacks have a modestly higher increased risk for more advanced increases in serum creatinine than non-Blacks.

Topics: Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Biomarkers; Black or African American; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; Chi-Square Distribution; Creatinine; Diuretics; Double-Blind Method; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Hydrochlorothiazide; Hypertension; Incidence; Kaplan-Meier Estimate; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United States; Up-Regulation

Black hypertensive patients are more resistant to angiotensin-converting enzyme (ACE) inhibitor monotherapy than White patients. This resistance can be overcome with the combination of ACE inhibitors with diuretics or calcium-channel blockers (CCBs).. The objective of this clinical investigation was to evaluate the antihypertensive effectiveness of monotherapy with the ACE inhibitor benazepril or the CCB amlodipine and their combination in Black and White hypertensive patients in two separate studies.. This was a post hoc analysis of data from two separate studies, pooled because of their similarities, to increase the sample size. Outpatient Black and White hypertensive patients were selected for these studies. In study H2303, 201 patients of both sexes and races, whose mean seated diastolic blood pressure (MSDBP) was ≥95 mmHg after 4 weeks of single-blind treatment with benazepril 40 mg/day, were randomized into two groups. Group 1 received benazepril 40 mg/day and group 2 received amlodipine/benazepril 5/40 mg/day, which was uptitrated to amlodipine/benazepril 10/40 mg/day at week 4 of the study. In study H2304, 812 similar patients, whose MSDBP was ≥95 mmHg after 4 weeks of single-blind treatment with amlodipine 10 mg/day, were randomized into three groups. Group 1 received amlodipine/benazepril 10/20 mg/day, uptitrated to amlodipine/benazepril 10/40 mg/day after 2 weeks. Group 2 received amlodipine/benazepril 10/20 mg/day. Group 3 received amlodipine 10 mg/day. All three groups were followed up for 6 additional weeks.. This report presents the results of post hoc analysis of pooled data from two separate but similar studies. Combination therapy resulted in greater lowering of MSDBP and mean seated systolic blood pressure (MSSBP) than monotherapy with either benazepril or amlodipine (p < 0.001). With respect to combination therapy, the combination of amlodipine/benazepril 10/20 mg/day resulted in greater blood pressure (BP) reductions in White patients than in Black patients (p < 0.004). In contrast, the combination of amlodipine/benazepril 10/40 mg/day resulted in similar BP reductions in both Black and White hypertensive patients. There were no serious clinical or metabolic side effects noted, with the exception of pedal edema, which was more common with amlodipine monotherapy.. This study showed that combination therapy with amlodipine/benazepril is more effective in BP lowering than monotherapy with the component drugs. Black hypertensive patients are responsive to the combination of amlodipine/benazepril; however, they require higher dose combinations for BP reductions similar to those achieved in White hypertensive patients.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Black People; Blood Pressure; Calcium Channel Blockers; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Single-Blind Method; White People

Hypertension is a prevalent condition that is closely associated with chronic complications in patients with diabetes. Fixed-dose combination therapy is currently recommended for the treatment of hypertension due to the advantage of reducing the pill burden. However, the effects of combination therapy may be diverse because of the different components.. We examined blood pressure reduction and metabolic alterations after amlodipine/benazepril and valsartan/hydrochlorothiazide treatment in patients with type 2 diabetes mellitus and hypertension and microalbuminuria.. This randomized, double-blind, parallel comparison, noninferiority clinical trial included patients with type 2 diabetes mellitus and hypertension and microalbuminuria detected within the past year. After a 2-week, placebo run-in period, patients were assigned to treatment with amlodipine/benazepril or valsartan/hydrochlorothiazide for 16 weeks. The primary end point was mean change in diastolic blood pressure. The prespecified boundary for noninferiority was 3.5 mm Hg of the mean change in diastolic blood pressure between treatments (amlodipine/benazepril minus valsartan/hydrochlorothiazide). If the upper limit of the 95% CI fell within 3.5 mm Hg, amlodipine/benazepril would be considered noninferior to valsartan/hydrochlorothiazide.. Of the 226 patients assessed for eligibility, 169 satisfied the inclusion/exclusion criteria and were assigned to a treatment group; 83 patients (54.2% male, mean age of 60.5 [10.0] years) in the amlodipine/benazepril group and 84 patients (64.3% male, mean age of 59.0 [10.6] years) in the valsartan/hydrochlorothiazide group received at least 1 dose of study medication and were included in the intention-to-treat population. In the per-protocol population, amlodipine/benazepril (n = 74) was noninferior to valsartan/hydrochlorothiazide (n = 78) with regard to the mean change in diastolic blood pressure (difference, -0.9 mm Hg; 95% CI, -3.5 to 1.6). The mean change in systolic blood pressure was not significantly different (2.4 mm Hg; 95% CI, -1.2 to 6.0) between study groups (P = 0.195) in the per-protocol population. However, data from the intention-to-treat population suggest that patients in the amlodipine/benazepril group may have better metabolic outcomes than those in the valsartan/hydrochlorothiazide group; specifically, a preservation of the estimated glomerular filtration rate (5.7 mL/min/1.73 m(2) [95% CI, 1.9 to 9.6]; P = 0.004) and improvements in glycosylated hemoglobin (-0.5% [95% CI, -0.7 to -0.2]; P < 0.001), fasting triglycerides (-0.4 mmol/L [95% CI, -0.7 to -0.2]; P = 0.002), HDL-C (0.07 mmol/L [95% CI, 0.01 to 0.12]; P = 0.022), and uric acid (-57.5 μmol/L [95% CI, -74.8 to -40.3]; P < 0.001). There were no significant differences in adverse effects between groups, with the exception of more respiratory disorders in the amlodipine/benazepril group than in the valsartan/hydrochlorothiazide group (17 vs 5; P = 0 .006).. The study results suggest that amlodipine/benazepril is noninferior to valsartan/hydrochlorothiazide with regard to blood pressure reduction and that this combination exerts beneficial effects on renal function, glucose control, HDL-C, and triglyceride levels compared with valsartan/hydrochlorothiazide. However, respiratory adverse events (particularly coughing) were more frequently reported in the amlodipine/benazepril group. ClinicalTrials.gov identifier: NCT01375322.

Topics: Aged; Albuminuria; Amlodipine; Analysis of Variance; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Biomarkers; Blood Glucose; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Diuretics; Double-Blind Method; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hydrochlorothiazide; Hypertension; Lipids; Male; Middle Aged; Prospective Studies; Taiwan; Tetrazoles; Time Factors; Treatment Outcome; Uric Acid; Valine; Valsartan

To study the effect of peroxisome proliferator activated receptor γ (PPAR-γ) agonist on the angiotensin converting enzyme 2 (ACE2) mRNA expression in monocyte-derived macrophages of essential hypertensive patients.. Totally 57 essential hypertensive patients were randomly divided into three groups: conventional treatment group (n=18), telmisartan group (n=19), and benazepril group (n=20); 20 patients with normal blood pressure were also selected as the control group. Monocyte-derived macrophages were isolated from blood samples of patients in all four groups. The expression of ACE2 mRNA in monocyte-derived macrophages was detected by RT-PCR before treatment and 4 and 12 weeks after treatment.. Four and 12 weeks after treatment, the systolic pressure and diastolic pressure of telmisartan group and benazepril group were significantly lower than that of the conventional treatment group (all P<0.01), and the systolic pressure and diastolic pressure of telmisartan group were significantly lower than that of the benazepril group(both P<0.01) .The expression of ACE2 mRNA in monocyte-derived macrophages were significantly lower in essential hypertensive patients than that in control group (P<0.01). After having been treated for 4 weeks and 12 weeks, the expression of ACE2 mRNA in monocyte-derived macrophages of hypertensive patients in telmisartan and benazepril groups were significantly higher than that in conventional treatment group (all P<0.01), and the expression of ACE2 mRNA in telmisartan group was significantly higher than that in benazepril group (both P<0.01).. PPAR-γ agonist could increase the ACE2 mRNA expression in monocyte-derived macrophages of essential hypertensive patients.

Topics: Aged; Angiotensin-Converting Enzyme 2; Benzazepines; Benzimidazoles; Benzoates; Female; Humans; Hypertension; Macrophages; Male; Middle Aged; Peptidyl-Dipeptidase A; PPAR gamma; RNA, Messenger; Telmisartan

Few studies have examined the effect of the angiotensin II type I receptor (AT1R) A1166C polymorphism on the antihypertensive effect of the angiotensin-converting-enzyme inhibitor benazepril in patients with hypertension, and no such studies have performed analysis using the Family-Based Association Test (FBAT), The aim of our study was to examine the association between AT1R A1166C gene polymorphism and the antihypertensive effect of benazepril using the FBAT.. A total of 864 patients (aged, 26-62 years) with essential hypertension were identified in an epidemiological survey and enrolled in this study. Blood pressure (BP) was measured before and after 16 days of treatment with benazepril (10 mg/day). The association between the A1166C gene polymorphism and the antihypertensive effect of benazepril was assessed by FBAT. The frequencies of alleles A and C were 95.1% and 4.9%, respectively. FBAT analysis revealed that the C allele was significantly associated with high baseline diastolic BP (Z = 2.041, p = 0.041), decreased systolic BP after treatment (Z = 2.549, p = 0.011), and decreased diastolic BP after treatment (Z = 2.320, p = 0.020).. Our results, determined using the FBAT, are the first evidence that the AT1R A1166C polymorphism may increase the antihypertensive effect of benazepril in patients with hypertension.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Female; Gene Frequency; Genetic Association Studies; Genetic Linkage; Genotype; Humans; Hypertension; Male; Middle Aged; Nuclear Family; Polymorphism, Genetic; Receptor, Angiotensin, Type 1

To evaluate the efficacy and tolerability of the fixed combination of amlodipine 5 mg/benazepril 10 mg once-daily therapy, compared with benazepril, 10 mg, monotherapy in patients with mild and moderate hypertension, and to evaluate the 24 h antihypertensive efficacy and the duration of action by ambulatory blood pressure monitoring.. In a multicenter, randomized, double-blind, parallel controlled trial, 356 cases of hypertensive patients after 2 weeks wash-out, and then given 4 weeks of benazepril 10 mg monotherapy, 220 patients with mean seated diastolic blood pressure (SeDBP) remained ≥ 90 mm Hg (1 mm Hg = 0.133 kPa) were randomly divided into benazepril 10 mg/amlodipine 5 mg (BZ10/AML5) fixed-dose combination therapy group (once a day, n = 113), and benazepril monotherapy group (daily 20 mg, n = 107). In the two groups the patients with SeDBP ≥ 90 mm Hg were doubled the dosage of the initial regimen at the end of 4-week treatment for additional 4 weeks, and the patients with SeDBP < 90 mm Hg remained the initial regimen for additional 4 weeks. The primary endpoint was to evaluate the improvement of SeDBP at the end of 8-week treatment. There were 74 patients (the combination therapy group n = 38, monotherapy therapy group n = 36) completed the 24 h ambulatory blood pressure monitoring which was included in the final efficacy analysis.. The randomized, double-blind treatment for 8 weeks, the mean value of SeDBP reduction, the reaching target blood pressure rate and total successful response rate to the treatment (a SeDBP < 90 mm Hg or a decrease of 10 mm Hg or more from baseline) were (11.7 ± 6.8) mm Hg, 65.7% and 88.5% in the combination therapy group, respectively, and were (7.7 ± 6.9) mm Hg, 35.5% and 65.5% in the monotherapy group, respectively. There were statistically significant difference between the combination therapy and the monotherapy groups in all the 3 indexs (P < 0.001). The fixed combination significantly reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) values throughout the 24 h. The trough to peak ratios of DBP/SBP in the fixed compound of benazepril/amlodipine (10 mg/5 mg) and benazepril (20 mg) alone were 83.1%/76.0% and 85.8%/79.5%, respectively. Adverse events rates were 16.8% in the combination therapy group and 35.5% in the monotherapy group (P < 0.001).. The combination therapy with benazepril/amlodipine was superior to benazepril monotherapy and was well tolerated in patients with essential hypertension and allowing a satisfactory BP control for 24 hours.

Topics: Adult; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Calcium Channel Blockers; Double-Blind Method; Drug Combinations; Female; Humans; Hypertension; Male; Middle Aged

To compare effects of valsartan and benazepril on erythropoietin (EPO) levels in essential hypertensive patients with normal renal function.. Sixty essential hypertensive patients were randomly divided into valsartan group (n=30, valsartan 80 mg/day) and benazepril group (n=30, benazepril 10 mg/day). Plasma EPO and hemoglobin (Hb) levels were measured at the start of and at 4 and 8 weeks during the treatments.. EPO and Hb levels were all in normal range in the two groups. Valsartan decreased EPO levels from 14.179∓3.214 U/L (baseline) to 12.138∓2.926 U/L (P<0.05) and Hb levels from 144.32∓13.84 g/L (baseline) to 135.16∓14.78 U/L (P<0.05). Benazepril treatment did not resulted in any obvious changes in EPO or Hb levels (P>0.05).. Valsartan may lower EPO and Hb levels in patients with essential hypertension, while benazepril does not have such effects. The safety of valsartan in anemic hypertensive patients should be further investigated.

Topics: Adult; Aged; Aged, 80 and over; Benzazepines; Erythropoietin; Female; Hemoglobins; Humans; Hypertension; Male; Middle Aged; Tetrazoles; Valine; Valsartan

This multicentre, double-blind, trial in subjects with severe hypertension compared the efficacy and tolerability of two parallel drug regimens: A/B (amlodipine/benazepril: 5/20 or 10/40 mg daily, if necessary) with A (amlodipine: 5 or 10 mg daily, if necessary). The principal dependent variable was the proportion of patients achieving goal blood pressures (BP<140/90 mm Hg or BP<130/80 mm Hg in diabetes or chronic kidney disease) in the two groups within 6 weeks. In the 259 randomized subjects, BP control rates were higher with A/B at 2, 4 and 6 weeks (10.5, 22, and 33.6%, respectively) compared with A (5.7, 16, and 25.8 %, respectively). Corresponding trended BP reductions from baseline at 2, 4 and 6 weeks were about 5 mm Hg greater with A/B (-21+/-16, -26+/-17 and -30+/-17 mm Hg, respectively, compared with A (-16+/-17, -23+/-18 and 25+/-19 mm Hg, respectively, P<0.01). Both regimens were well tolerated; incidences of peripheral oedema at weeks 4 and 6 were similar (A/B: 13 and 20% versus A: 20 and 22%, P=not significant). We conclude that titration of amlodipine and benazepril in single-pill combinations is more effective than titration of amlodipine alone for rapid BP control in patients with severe hypertension.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amlodipine; Antihypertensive Agents; Benzazepines; Chronic Disease; Diabetes Complications; Drug Therapy, Combination; Edema; Female; Humans; Hypertension; Kidney Diseases; Male; Middle Aged; Treatment Outcome; Young Adult

The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality. We assessed the effects of these drug combinations on progression of chronic kidney disease.. ACCOMPLISH was a double-blind, randomised trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12.5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals. Progression of chronic kidney disease, a prespecified endpoint, was defined as doubling of serum creatinine concentration or end-stage renal disease (estimated glomerular filtration rate <15 mL/min/1.73 m(2) or need for dialysis). Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00170950.. The trial was terminated early (mean follow-up 2.9 years [SD 0.4]) because of superior efficacy of benazepril plus amlodipine compared with benazepril plus hydrochlorothiazide. At trial completion, vital status was not known for 143 (1%) patients who were lost to follow-up (benazepril plus amlodipine, n=70; benazepril plus hydrochlorothiazide, n=73). All randomised patients were included in the ITT analysis. There were 113 (2.0%) events of chronic kidney disease progression in the benazepril plus amlodipine group compared with 215 (3.7%) in the benazepril plus hydrochlorothiazide group (HR 0.52, 0.41-0.65, p<0.0001). The most frequent adverse event in patients with chronic kidney disease was peripheral oedema (benazepril plus amlodipine, 189 of 561, 33.7%; benazepril plus hydrochlorothiazide, 85 of 532, 16.0%). In patients with chronic kidney disease, angio-oedema was more frequent in the benazepril plus amlodipine group than in the benazepril plus hydrochlorothiazide group. In patients without chronic kidney disease, dizziness, hypokalaemia, and hypotension were more frequent in the benazepril plus hydrochlorothiazide group than in the benazepril plus amlodipine group.. Initial antihypertensive treatment with benazepril plus amlodipine should be considered in preference to benazepril plus hydrochlorothiazide since it slows progression of nephropathy to a greater extent.. Novartis.

Topics: Aged; Albuminuria; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; Creatinine; Disease Progression; Diuretics; Double-Blind Method; Drug Combinations; Female; Glomerular Filtration Rate; Humans; Hydrochlorothiazide; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Risk Factors

Topics: Amlodipine; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Drug Therapy, Combination; Humans; Hydrochlorothiazide; Hypertension

The aim of this study was to determine which combination therapy in patients with hypertension and diabetes most effectively decreases cardiovascular events.. The ACCOMPLISH (Avoiding Cardiovascular Events Through COMbination Therapy in Patients Living With Systolic Hypertension) trial compared the outcomes effects of a renin-angiotensin system blocker, benazepril, combined with amlodipine (B+A) or hydrochlorothiazide (B+H). A separate analysis in diabetic patients was pre-specified.. A total of 6,946 patients with diabetes were randomized to treatment with B+A or B+H. A subgroup of 2,842 diabetic patients at very high risk (previous cardiovascular or stroke events) was also analyzed, as were 4,559 patients without diabetes. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for angina, resuscitated arrest, and coronary revascularization.. In the full diabetes group, the mean achieved blood pressures in the B+A and B+H groups were 131.5/72.6 and 132.7/73.7 mm Hg; during 30 months, there were 307 (8.8%) and 383 (11.0%) primary events (hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.68 to 0.92, p = 0.003). For the diabetic patients at very high risk, there were 195 (13.6%) and 244 (17.3%) primary events (HR: 0.77, 95% CI: 0.64 to 0.93, p = 0.007). In the nondiabetic patients, there were 245 (10.8%) and 296 (12.9%) primary events (HR: 0.82, 95% CI: 0.69 to 0.97, p = 0.020). In the diabetic patients, there were clear coronary benefits with B+A, including both acute clinical events (p = 0.013) and revascularizations (p = 0.024). There were no unexpected adverse events.. In patients with diabetes and hypertension, combining a renin-angiotensin system blocker with amlodipine, compared with hydrochlorothiazide, was superior in reducing cardiovascular events and could influence future management of hypertension in patients with diabetes. (Avoiding Cardiovascular Events Through COMbination Therapy in Patients Living With Systolic Hypertension [ACCOMPLISH]; NCT00170950).

Topics: Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Coronary Disease; Diabetes Complications; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Risk Factors

Topics: Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Calcium Channel Blockers; Diuretics; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Treatment Outcome

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Calcium Channel Blockers; Double-Blind Method; Drug Therapy, Combination; Humans; Hydrochlorothiazide; Hypertension; Risk Assessment

Left ventricular hypertrophy, a major cardiovascular risk factor for morbidity and mortality, is commonly caused by arterial hypertension. The renin-angiotensin-aldosterone system may contribute to the pathogenesis of left ventricular hypertrophy. The Assessment of Lotrel in Left Ventricular Hypertrophy and Hypertension Study compared a single-pill combination of amlodipine/benazepril at doses 5.0/20.0 mg, 5.0/40.0 mg, and 10.0/40.0 mg with hydrochlorothiazide/benazepril at doses 12.5/20.0 mg, 12.5/40.0 mg, and 25.0/40.0 mg on the reduction of left ventricular mass index measured by cardiac MRI in stage 2 hypertensive patients over 52 weeks of treatment in a randomized clinical trial. A total of 125 male and female patients, > or =55 years of age, with echocardiographic left ventricular hypertrophy and high-risk hypertension defined as blood pressure > or =160/100 mm Hg or current antihypertensive treatment were enrolled. After 52 weeks of treatment, left ventricular mass index was significantly reduced from baseline with amlodipine/benazepril (mean: 10.16 g/m(2)) or hydrochlorothiazide/benazepril (mean: 6.74 g/m(2); both P<0.0001), with a mean difference between treatment groups of 3.36 g/m(2) (P=0.16). No significant treatment differences were observed in subgroups defined by age, male gender, race, diabetes status, or dose level. However, in female patients, left ventricular mass index reduction was greater with amlodipine/benazepril (P=0.02). Both treatments were well tolerated.

Topics: Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Calcium Channel Blockers; Diuretics; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Female; Heart Ventricles; Humans; Hydrochlorothiazide; Hypertension; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Male; Middle Aged; Risk Factors; Sex Characteristics; Treatment Outcome

In order to determine whether hypertension would develop in dogs with chronic renal failure, we performed 7/8 renal ablation in 6 healthy dogs and compared pre- and post-ablation blood pressures determined by telemetry. One month after the renal ablation, blood urea nitrogen and creatinine were significantly increased (p<0.05), creatinine clearance was decreased (p<0.05), and blood pressure was increased significantly (p<0.05). Simultaneously, plasma renin activity, angiotensin I and II, and aldosterone were elevated significantly (p<0.05) compared with the values obtained from 11 healthy dogs with intact renal function. The dogs with induced renal failure and hypertension were administered an angiotensin-converting enzyme inhibitor, benazepril hydrochloride, once daily for 2 weeks at 2 mg/kg body weight, and changes in blood pressure and the renin-angiotensin-aldosterone (RAA) system were determined. During the administration of benazepril hydrochloride, blood pressure, angiotensin II and aldosterone decreased significantly (p<0.05) and, upon discontinuation of administration, increased to the pre-administration levels (p<0.05). Plasma renin activity and angiotensin I showed no significant changes throughout the administration study. These results provide experimental evidence that hypertension develops in dogs with chronic renal failure through mechanisms involving the RAA system and demonstrate that benazepril hydrochloride improves renal hypertension in dogs.

Topics: Aldosterone; Angiotensin I; Angiotensin II; Animals; Antihypertensive Agents; Benzazepines; Blood Pressure; Dog Diseases; Dogs; Female; Hypertension; Kidney Failure, Chronic; Male; Renin

Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) is an outcome study investigating aggressive antihypertensive combination treatment. It has achieved a larger fraction of overall patients with blood pressure (BP) <140/90 mmHg (73.3%) and diabetic patients <130/80 mmHg (43.3%) at 12 months of follow-up than any other large outcomes trial. We have analyzed baseline predictors of BPs and BP control at 12 months.. Blinded baseline and 12-month BP was available in 10,173 patients of whom 6132 had diabetes. Univariate and multivariate logistic regression models were used for BP control at 12 months; simple and multiple regression models were used for absolute BP value at 12 months. A stepwise procedure was used to select significant predictors in multivariate analyses.. Mean (SD) BP fell from 145.5/80.2 mmHg (18.2/10.7 mmHg) at randomization to 132.7/74.7 mmHg (16/9.6 mmHg) at 12 months. The main baseline predictors of achieving BP control were region (USA), Caucasian race and taking lipid-lowering drugs. The predictors of uncontrolled BP were higher baseline systolic BP values, more previous antihypertensive medications, proteinuria and previous thiazide use.. Patients in the USA, Caucasians and patients taking lipid-lowering therapy were most likely to reach BP targets with combination therapy. Strong predictors of uncontrolled hypertension were more severe hypertension, an established need for more antihypertensive drugs and target organ damage.

Topics: Aged; Amlodipine; Antihypertensive Agents; Benzazepines; Blood Pressure; Dose-Response Relationship, Drug; Double-Blind Method; Drug Resistance; Drug Therapy, Combination; Female; Finland; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Racial Groups; Risk Assessment; Scandinavian and Nordic Countries; Treatment Outcome; United States

This study sought to compare the antihypertensive efficacy and tolerability of a fixed-dose combination with amlodipine/benazepril with that of amlodipine monotherapy in Chinese hypertensive subjects.. This multicenter, double-blind, 8-week study randomized 111 patients to fixed-dose amlodipine besylate/benazepril HCl (2.5/5 mg/day titrated to 5/10 mg/day as needed at week 4 to reach goal blood pressure (BP) <140/90 mmHg) or amlodipine besylate monotherapy (5 mg/day titrated to 10 mg/day as needed). At week 8, patients randomized to combination therapy compared with monotherapy had a comparable BP control rate (56.0% vs. 46.2%; p = 0.32). Fixed-dose combination resulted in similar reductions in sitting systolic (SBP) and diastolic BP (DBP) compared with monotherapy (SBP: -19.3 +/- 12.5 vs. -20.9 +/- 13.3 mmHg; DBP: -9.2 +/- 10.4 vs. -11.3 +/-9.3 mmHg; both p=NS). Safety profiles did not differ between groups, but cough was more common in the combination group (11.0% vs. 0%; p = 0.013).. In this group of patients, comparable antihypertensive effects were seen with the fixed-dose combination therapy, compared with amlodipine monotherapy. Both treatments appeared well tolerated in the studied population, but cough was more common in the fixed-dose combination group.

Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Calcium Channel Blockers; Double-Blind Method; Drug Combinations; Female; Humans; Hypertension; Male; Middle Aged

The Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial is the first cardiovascular outcome trial designed to compare initial use of 2 different fixed-dose antihypertensive regimens, benazepril plus hydrochlorothiazide vs benazepril plus amlodipine, on cardiovascular end points in hypertensive patients at high cardiovascular risk secondary to previous major events or presence of diabetes mellitus (DM). Of the 11,464 patients, 60.4% had DM. Compared with non-DM patients, DM patients were less likely to have previous myocardial infarctions (15% vs 37%) or strokes (8% vs 21%). Those with DM were more likely to be female (43% vs 34%), black (15% vs 8%), overweight (body mass index, 32 vs 29 kg/m(2)). At baseline, DM patients were more likely to have the metabolic syndrome, manifested by higher levels of fasting glucose (145 vs 101 mg/dL) and triglycerides (178 vs 150 mg/dL) and slightly lower high-density lipoprotein cholesterol values (48 vs 51 mg/dL) compared to the non-DM cohort. Although estimated glomerular filtration rate (80 vs 76 mL/min/1.73 m(2)) was similar in the DM and non-DM groups, presence of both albuminuria (8.7% vs 3.5%) and microalbuminuria (29% vs 20%) were more prevalent in the DM group. After 6 months of treatment, blood pressure control rates (<140/90 mm Hg) using blinded data (both therapeutic groups combined) for DM demonstrated that 42.8% of DM patients had blood pressure levels <130/80 mm Hg. ACCOMPLISH will provide valuable guidance on optimizing treatment strategies in hypertensive patients at high cardiovascular risk with and without DM.

Topics: Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Glucose; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus; Diuretics; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Prevalence; Time Factors; Treatment Outcome; United States

The optimal combination drug therapy for hypertension is not established, although current U.S. guidelines recommend inclusion of a diuretic. We hypothesized that treatment with the combination of an angiotensin-converting-enzyme (ACE) inhibitor and a dihydropyridine calcium-channel blocker would be more effective in reducing the rate of cardiovascular events than treatment with an ACE inhibitor plus a thiazide diuretic.. In a randomized, double-blind trial, we assigned 11,506 patients with hypertension who were at high risk for cardiovascular events to receive treatment with either benazepril plus amlodipine or benazepril plus hydrochlorothiazide. The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization.. The baseline characteristics of the two groups were similar. The trial was terminated early after a mean follow-up of 36 months, when the boundary of the prespecified stopping rule was exceeded. Mean blood pressures after dose adjustment were 131.6/73.3 mm Hg in the benazepril-amlodipine group and 132.5/74.4 mm Hg in the benazepril-hydrochlorothiazide group. There were 552 primary-outcome events in the benazepril-amlodipine group (9.6%) and 679 in the benazepril-hydrochlorothiazide group (11.8%), representing an absolute risk reduction with benazepril-amlodipine therapy of 2.2% and a relative risk reduction of 19.6% (hazard ratio, 0.80, 95% confidence interval [CI], 0.72 to 0.90; P<0.001). For the secondary end point of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke, the hazard ratio was 0.79 (95% CI, 0.67 to 0.92; P=0.002). Rates of adverse events were consistent with those observed from clinical experience with the study drugs.. The benazepril-amlodipine combination was superior to the benazepril-hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events. (ClinicalTrials.gov number, NCT00170950.)

Topics: Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; Diuretics; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Kaplan-Meier Estimate; Male; Middle Aged; Risk

Aldosterone controls sodium balance and intravascular volume, and thus helps regulate blood pressure. Secretion of aldosterone is mainly regulated at the level of expression of the aldosterone synthase (CYP11B2) gene. The intron-2 conversion polymorphism of CYP11B2 was suggested to lead to overexpression of the gene, and may therefore have potential to predict the blood pressure response of patients with essential hypertension to angiotensin-converting enzyme inhibitors (ACEIs).. To investigate the association between the intron-2 conversion polymorphism and the blood pressure response to ACEIs in a hypertensive cohort.. After a 2-week, single-blind, placebo run-in period, ACEIs were administered for 6 weeks to 509 patients with mild-to-moderate essential hypertension. The intron-2 conversion polymorphism was examined by polymerase chain reaction.. The IwIw genotype was observed in 106 patients (20.8%), the IwIc genotype in 251 patients (49.3%), and the IcIc genotype in 152 patients (29.9%). After 6 weeks of treatment the reductions in diastolic blood pressure were significantly greater in patients carrying IcIc or IwIc compared with IwIw genotypes (9.2 +/- 7.2 or 9.2 +/- 7.1 versus 6.4 +/- 6.6 mmHg, respectively; analysis of variance, P = 0.001). Stepwise multiple regression analysis showed that significant predictors of diastolic blood pressure reduction at 6 weeks were baseline diastolic blood pressure (P < 0.001), intron-2 conversion genotype (P = 0.006) and sex (P = 0.030).. The intron-2 conversion polymorphism was related to the diastolic blood pressure lowering response in hypertensive patients treated with ACEIs. Interindividual variation in the efficacy of antihypertensive medications may therefore be influenced by genetic factors.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Cytochrome P-450 CYP11B2; Female; Genotype; Humans; Hypertension; Imidazolidines; Introns; Male; Middle Aged; Polymorphism, Single Nucleotide

Clinical practice guidelines recommend blockers of the renin-angiotensin system alone or in combination with other agents to reduce blood pressure and albuminuria in patients with type 2 diabetes. Dihydropyridine calcium channel blockers, however, may lower blood pressure but not albuminuria in these patients. Here we tested the hypothesis that combining an ACE inhibitor with either a thiazide diuretic or a calcium channel blocker will cause similar reductions in blood pressure and albuminuria in hypertensive type 2 diabetics. We conducted a double blind randomized controlled trial on 332 hypertensive, albuminuric type 2 diabetic patients treated with benazepril with either amlodipine or hydrochlorothiazide for 1 year. The trial employed a non-inferiority design. Both combinations significantly reduced the urinary albumin to creatinine ratio and sitting blood pressure of the entire cohort. The percentage of patients progressing to overt proteinuria was similar for both groups. When we examined patients who had only microalbuminuria and hypertension we found that a larger percentage of the diuretic and ACE inhibitor normalized their albuminuria. We conclude that initial treatment using benzaepril with a diuretic resulted in a greater reduction in albuminuria compared to the group of ACE inhibitor and calcium channel blocker. In contrast, blood pressure reduction, particularly the diastolic component, favored the combination with amilodipine. The dissociation between reductions in blood pressure and albuminuria may be related to factors other than blood pressure.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diuretics; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Treatment Outcome

Evidence suggests that transforming growth factor-beta1 (TGF-beta(1)) is associated with target organ damage in hypertension. This study aimed to investigate the relationship between TGF-beta(1) levels and kidney damage and renoprotective effects of angiotensin-converting enzyme inhibitor and/or angiotensin II type 1 receptor blocker in patients with essential hypertension (EH).. A total of 156 patients with EH were enrolled and grouped according to albumin-to-creatinine ratio (ACR). Of these, 90 patients with EH underwent a 12-week antihypertensive trial with administration of benazepril, valsartan or both. Serum TGF-beta(1), plasma angiotensin (Ang) II and urinary albumin were quantified by immunoassays.. Serum TGF-beta1, plasma Ang II and ACR were highly elevated in patients with EH (P < 0.01). There was a positive correlation between serum TGF-beta1 levels and ACR (r = 0.53, P < 0.01). Significant decreases in TGF beta1 and ACR were obtained in all groups at the end of 12-week antihypertensive therapy compared to the baseline values, with the combined group to a greater extent (P < 0.01). Plasma Ang II levels were significantly decreased in the benazepril group but increased in the valsartan group (P < 0.05) while no significant change was observed in the combined group.. TGF-beta(1) is highly elevated and strongly associated with urinary albumin excretion in patients with EH. Treatment with benazepril or valsartan attenuates serum TGF-beta(1) levels and microalbuminuria with the combined therapy receiving the greater effect. TGF-beta(1) could be a potential surrogate marker in monitoring the development and progression of kidney damage in EH.

Topics: Administration, Inhalation; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Double-Blind Method; Female; Humans; Hypertension; Kidney; Kidney Diseases; Male; Middle Aged; Prospective Studies; Tetrazoles; Transforming Growth Factor beta1; Valine; Valsartan

ACCOMPLISH is the first trial designed to compare the effects on major fatal and non-fatal cardiovascular endpoints of two forms of antihypertensive combination therapy: benazepril plus hydrochlorothiazide and amlodipine plus benazepril in hypertensive patients at high cardiovascular risk. Enrollment for this trial is now complete and this report describes the clinical characteristics of the study cohort. Patients with hypertension and a previous history of cardiovascular events, strokes or diabetes mellitus were randomized to double-blind treatment with either of the two combination regimens. The data in this report detail the clinical history and demographic characteristics in patients immediately prior to randomization to study drugs. A total of 11,454 patients were randomized. Mean age (+/-SD) was 68.4+/-6.9 years, 60% were men, and 1360 (12%) were African American. Mean body mass index (BMI) was 31.0+/-6.3 kg/m(2). At study entry, 46% of patients had a history of acute coronary syndromes, coronary artery bypass grafts or percutaneous coronary interventions; 13% had a history of stroke. A history of diabetes mellitus was reported in 6928 (60%) of patients. Mean blood pressure at baseline (on prior hypertension therapy) was 145.4/80.0 mmHg; only 38% of patients had a BP less than 140/90 mmHg. Overall, 97% of patients had received previous antihypertensive treatment (74% on at least two drugs); 53% were on oral diabetes therapy or insulin, 68% on anti-lipid therapy and 63% on anti-platelet agents. In summary, the ACCOMPLISH trial has recruited hypertensive patients at high risk of cardiovascular morbidity and mortality. It is noteworthy that the mean BMI of 31 in this cohort is clearly above the accepted diagnostic criterion of obesity and that 60% of patients are diabetic, possibly reflecting secular trends in clinical disease.

Topics: Aged; Amlodipine; Antihypertensive Agents; Benzazepines; Body Mass Index; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Myocardial Infarction; Patient Selection; Scandinavian and Nordic Countries; Stroke; United States

This study compared the efficacy and safety of amlodipine/benazepril (10/40 mg/day and 10/20 mg/day) with amlodipine 10 mg/day in patients whose blood pressure (BP) was not adequately controlled with amlodipine monotherapy.. After a lead-in period with amlodipine monotherapy, 812 non-responder patients (mean sitting diastolic BP > or =95 mmHg) were randomized to one of three treatment groups. Ambulatory BP monitoring was conducted in 276 patients.. Treatment with amlodipine/benazepril 10/40 mg/day and 10/20 mg/day resulted in a decrease of mean sitting systolic and mean sitting diastolic BP by 13.3/12.7 mmHg and 12.1/11.6 mmHg, respectively, compared with monotherapy (6.6/8.5 mmHg) (p < 0.0001). Both combinations resulted in more responders than monotherapy (74% and 65% vs. 54%; p < 0.0001 and p < 0.0085, respectively). Amlodipine/benazepril 10/40 mg/day and 10/20 mg/day decreased ambulatory systolic and diastolic BP by 9.9/6.7 mmHg and 7.4/5.2 mmHg compared with monotherapy (p < 0.0001). The incidence of pedal edema was lower in the amlodipine/benazepril combinations compared with monotherapy (4.5%, 5.5% vs. 9.2%, respectively, p=NS). No significant metabolic side-effects were noted among the combination groups.. Amlodipine/benazepril combinations were well tolerated and resulted in significant BP reductions and better BP responder rates than amlodipine monotherapy.

Topics: Adult; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged

ACCOMPLISH is a "new-generation" hypertension trial assessing single-tablet combination therapy for initial treatment of high-risk hypertension. At baseline, 97% of subjects were treated with anti-hypertensive medication at entry, but only 37% of participants had blood pressure (BP) control (<140/90 mmHg). Single-tablet combination therapy may improve control rates.. The mean BP change from baseline at the end of 6 months (the time point when subjects should have had all of the drug titrations to achieve BP control) was examined for 10,704 randomized patients. Within-group changes were examined using t-tests. Comparisons between subgroups were made using analysis of variance (ANOVA) and covariance (ANCOVA).. Mean (+/-SD) BP fell from 145+/-18/80+/-11 mmHg at randomization to 132+/-16/74+/-10 mmHg. The 6-month BP control rate was 73% in the overall trial (78% in the US), 43% in diabetics and 40% in patients with renal disease. Of the patients uncontrolled, 61% were not on maximal medications, suggesting potential increases in control rates. Serious hypotensive events occurred in 1.8% of participants.. ACCOMPLISH BP control rates are the highest of any multi-national trial to date. Whereas current guidelines recommend combination therapy only for stage 2 hypertension, in this trial it is expedient and safe for both stage 1 and 2 hypertension.

Topics: Amlodipine; Antihypertensive Agents; Benzazepines; Blood Pressure; Double-Blind Method; Drug Therapy, Combination; Humans; Hydrochlorothiazide; Hypertension

To observe the efficacy and safety of zhongfu hypotension capsule (ZHC) in treating hypertension of yin-deficiency with sthenic-yang syndrome type.. Adopting the stratified, block randomized, double-blinded, double-dummy, positive parallel controlled, multi-centered clinical trial method, the tested group was treated by orally taken 3 capsules of ZHC (0.5 g/capsule) twice a day, and the control group was treated by orally taken Lotensin Tablet 1 tablet (10 mg/tab.) once a day. And all received the adiaphorous drug with the dosage-form mimic to that used in the tested group. The therapeutic course was 4 weeks for both groups.. The markedly effective rate and the total effective rate in reducing blood pressure was 58.65% and 79.81% respectively in the tested group, and 60.51% and 78.34% respectively in the control group; while the markedly effective rate and the total effective rate for alleviating TCM syndrome was 21.15% and 78.85% in the tested group, and 25.48% and 86.62% in the control group respectively. Comparisons between the two groups showed insignificant difference (P > 0.05).. ZHC has good efficacy and is safety in treating hypertension.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Double-Blind Method; Drugs, Chinese Herbal; Female; Humans; Hypertension; Male; Middle Aged; Phytotherapy; Syndrome; Tablets; Yin Deficiency

Most patients with stage 2 hypertension require two or more antihypertensive agents in order to achieve the BP goals recommended in current treatment guidelines. Accordingly, combinations of two drugs with different mechanisms of antihypertensive action are widely used.. The aim of this randomized, double-blind, multicenter 12-week study was to compare the efficacy, safety, and tolerability of a combination of olmesartan medoxomil/hydrochlorothiazide (HCTZ) with that of benazepril plus amlodipine besylate in patients with stage 2 hypertension.. Patients were eligible for randomization following a 3- to 4-week placebo run-in period if they had either (i) mean seated DBP>or=90 mm Hg but<115 mm Hg and mean seated SBP>or=160 mm Hg but <200 mm Hg, or (ii) mean seated DBP>or=100 mm Hg but<115 mm Hg. The difference in mean seated SBP measured on two separate visits during the run-in period was required to beor=95 mm Hg and<115 mm Hg or SBP>145 mm Hg and

Topics: Amlodipine; Antihypertensive Agents; Benzazepines; Blood Pressure; Diastole; Drug-Related Side Effects and Adverse Reactions; Female; Goals; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Male; Middle Aged; Olmesartan Medoxomil; Systole; Tetrazoles; Treatment Outcome

To investigate the efficacy of 10 mg or 20 mg atorvastatin + long acting antihypertensive in carotid intima-medial thickness (IMT).. 151 patients of Han nationality in South China with mild hypertensive were randomly divided into 3 groups: atorvastatin 10 mg group (n = 50) receive 10 mg atorvastatin and amlodipine + benazepril; atorvastatin 20 mg group (n = 61) receive 20 mg atorvastatin and amlodipine + benazepril; the control group (n = 40) receive amlodipine + benazepril. The patients were detected IMT, vascular function, lipids and inflammatory factor in pretherapy and every 3 months.. atorvastatin 10 mg or 20 mg groups have significantly change contrast to control group: (1) IMT was decreased (P < 0.01). (2) Deltadia-P% and Deltadia-N% were increased (P < 0.01). (3) LDL-C level was decreased by 30% in a atorvastatin 10 mg group and 40.48% in 20 mg group respectively (P < 0.01).. Atorvastatin delays the development of atherosclerosis in hypertensive patients, improves endothelial function, and strengthens the effect of lipid-lowering.

Topics: Aged; Amlodipine; Anticholesteremic Agents; Antihypertensive Agents; Atorvastatin; Benzazepines; Carotid Arteries; China; Cholesterol, LDL; Dose-Response Relationship, Drug; Drug Therapy, Combination; Endothelium, Vascular; Female; Heptanoic Acids; Humans; Hypertension; Male; Middle Aged; Pyrroles; Time Factors; Treatment Outcome; Tunica Intima; Tunica Media

Our objective was to investigate the association between the -344C/T or A6547G polymorphism of the aldosterone synthase gene and the blood pressure response to angiotensin-converting enzyme inhibitors in a hypertensive cohort.. After a 2-week single-blind placebo run-in period, either benazepril or imidapril was administered for 6 weeks to 509 patients with mild to moderate essential hypertension. Polymerase chain reaction combined with restriction enzyme digestion was used to detect the 2 polymorphisms. The achieved changes in systolic and diastolic blood pressure were analyzed for their association with genotypes at the aldosterone synthase gene loci.. Regarding the -344C/T polymorphism, we observed the CC genotype in 53 patients (10.4%), the CT genotype in 204 (40.1%), and the TT genotype in 252 (49.5%). After 6 weeks of treatment, the reductions in diastolic blood pressure were significantly greater in patients carrying the TT or CT genotype compared with those carrying the CC genotype (9.1+/-7.0 mm Hg or 8.9+/-7.0 mm Hg versus 5.1+/-7.3 mm Hg, respectively; P=.001, ANOVA). Regarding the A6547G polymorphism, we observed the AA genotype in 19 patients (3.7%), the AG genotype in 184 (36.2%), and the GG genotype in 306 (60.1%). There were no significant differences in the blood pressure reductions after treatment among the 3 genotype groups, and there was no interaction between it and the -344C/T polymorphism. Stepwise multiple regression analysis showed that the significant predictors of diastolic blood pressure reduction at 6 weeks were baseline diastolic blood pressure (P<.001), -344C/T genotype (P=.007), and sex (P=.033).. The -344C/T variant, but not the A6547G variant, of the aldosterone synthase gene may be a determinant of the blood pressure response to angiotensin-converting enzyme inhibitors in hypertensive patients.

Topics: Administration, Oral; Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Asian People; Benzazepines; Blood Pressure; China; Cytochrome P-450 CYP11B2; Female; Humans; Hypertension; Imidazolidines; Male; Middle Aged; Polymorphism, Genetic; Severity of Illness Index; Single-Blind Method

Evidence suggests that renin-angiotensin-aldosterone system inhibition ameliorates endothelial dysfunction. The authors examined the effect of amlodipine besylate/benazepril HCl combination treatment compared with amlodipine besylate monotherapy in modulating endothelial dysfunction. This multicenter, double-blind, 12-week study randomized 70 hypertensive subjects with at least one other endothelial dysfunction risk factor to amlodipine besylate/benazepril HCl (5/20 mg/d force-titrated to 5/40 mg/d) or amlodipine besylate monotherapy (5 mg/d force-titrated to 10 mg/d). Both the combination and monotherapy produced significant median increases from baseline in percentage flow-mediated vasodilation (2.0% and 1.2%, respectively) and percentage change in percent flow-mediated vasodilation (25% and 16%, respectively). These improvements were numerically larger with combination treatment, but between-group differences did not achieve statistical significance. Reductions in systolic and diastolic blood pressure were significantly greater (P=.0452/P=.0297) with combination treatment (-18.6/-12.3 mm Hg) than with monotherapy (-14.8/-9.1 mm Hg). A highly positive correlation between change in systolic blood pressure and change in percent of flow-mediated vasodilation was demonstrated only for combination treatment.

Topics: Aged; Amlodipine; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Biomarkers; Blood Flow Velocity; Blood Pressure; Brachial Artery; Calcium Channel Blockers; Double-Blind Method; Drug Therapy, Combination; Endothelium, Vascular; Female; Humans; Hypertension; Male; Middle Aged; Risk Factors; Severity of Illness Index; Treatment Outcome; United States; Vasodilation

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.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diuretics; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Renin-Angiotensin System; Research Design; Sodium Chloride Symporter Inhibitors

The molecular mechanisms underlying essential hypertension are not fully elucidated. Although Benazepril is being widely used in antihypertensive medication, the agent is efficacious in only a portion of hypertensive patients. To evaluate the interaction of alpha-adducin gene Gly460Trp and angiotensin I-converting enzyme (ACE) gene I/D polymorphisms in regard to baseline blood pressure (BP) levels and the reductions of blood pressures after Benazepril treatment, we conducted an investigation of 954 Chinese hypertensive patients in Anhui province, China. We found that compared with the baseline systolic BP (SBP) of subjects with one ACE I allele and one alpha-adducin Trp allele, the baseline SBP of those with ACE DD and alpha-adducin Gly/Gly genotypes was significantly higher [Crude: beta(SE) = 7.83(3.09), p = .01; Adjusted: beta(SE) = 5.83(2.83), p = .04]. However, no associations were found between the interaction of ACE I/D and alpha-adducin Gly460Trp polymorphisms and the baseline diastolic BP or the BP response to Benazepril treatment. Our results suggested that the interaction effect of alpha-adducin Gly460Trp and ACE I/D polymorphisms might play a significant role in regulating baseline BP but not BP response to Benazepril.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Asian People; Benzazepines; Blood Pressure; Calmodulin-Binding Proteins; Drug Resistance; Female; Humans; Hypertension; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic

To compare the additional antihypertensive effects of an angiotensin-converting enzyme inhibitor (ACEI), a dihydropyridine calcium antagonist and a diuretic in patients whose hypertension is not controlled by full-dose angiotensin receptor blocker (ARB) monotherapy.. Individuals with an ambulatory blood pressure (ABP) that was not controlled by valsartan 160 mg once daily were allocated randomly to two groups: those in group A (n = 35) were assigned randomly to treatment with benazepril 20 mg once daily or chlorthalidone 12.5 mg once daily, whereas patients in group B (n = 29) were assigned randomly to benazepril 20 mg once daily or amlodipine 5 mg once daily. All individuals continued to receive background valsartan 160 mg once daily. After 5 weeks, patients crossed over to the alternative valsartan-based combination treatment of each group for a second 5-week period. Twenty-four-hour ABP monitoring was performed before the random allocation to groups and at the end of each randomized combination pharmacotherapy period.. Sixty-four individuals completed the study: 32 men and 32 women (mean +/- SD age 48.2 +/- 7.9 years, average 24-h ABP on valsartan monotherapy 143.4 +/- 12.6/87.7 +/- 7.8 mmHg). Significant additional antihypertensive effects on the average 24-h ABP were obtained with benazepril (8.6 +/- 8.8/6.3 +/- 6.7 mmHg), amlodipine (15.2 +/- 12.9/9.9 +/- 6.8 mmHg) and chlorthalidone (13.5 +/- 11.6/9.5 +/- 7.7 mmHg) (P < 0.001 for all additional antihypertensive effects). The additional effects of amlodipine and chlorthalidone added to valsartan were approximately 6/3.5 mmHg (P < 0.05) greater than that of benazepril.. In patients in whom hypertension was not controlled by full-dose ARB monotherapy, a diuretic, a calcium antagonist or an ACE inhibitor provided significant additional antihypertensive effect. The antihypertensive effects of the ARB-diuretic and the ARB-calcium antagonist combinations were superior to that of the ARB-ACE inhibitor combination.

Topics: Adolescent; Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Chlorthalidone; Cross-Over Studies; Diuretics; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Tetrazoles; Treatment Outcome; Valine; Valsartan

Assessment of vascular compliance may be a useful measurement of the clinical effects of antihypertensive treatment. Both angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers are known to improve vascular elasticity. A study was performed to test the hypothesis that combined therapy with an ACE inhibitor and a calcium channel blocker would have additive benefits on vascular compliance at similar levels of blood pressure (BP), as compared with monotherapy with an ACE inhibitor. This 12-week, double-blind study was a substudy of a larger clinical hypertension study conducted in patients with hypertension and type 2 diabetes. Subjects (N = 20) were randomized to either a fixed-dose combination of amlodipine besylate/benazepril HCl or to enalapril monotherapy. BP, heart rate, large- and small-vessel compliance, systemic vascular resistance, and urinary microalbumin excretion were assessed at baseline and after treatment. Both treatments were similarly effective in lowering BP, reducing systemic vascular resistance, and decreasing urinary microalbumin excretion. Improvement in large-vessel compliance was significantly greater among subjects who received ACE-inhibitor/calcium channel blocker combination therapy (52%) as compared with those who received ACE-inhibitor monotherapy (32%; p < 0.05). No significant change in small-vessel compliance was observed with either treatment. Greater improvement in large-vessel compliance with combination therapy was independent of BP lowering.

Topics: Albuminuria; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Calcium Channel Blockers; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Humans; Hypertension; Male; Middle Aged; Natriuresis; Vascular Resistance

To explore the effect of simvastatin on myocardiac fibrosis in patients with essential hypertension (EH).. Sixty EH patients were randomly assigned into 2 groups: Benazepril (10 mg/d) group (n = 28) and simvastatin (20 mg/d) + benazepril (10 mg/d) group. Procollagen type III aminoterminal peptide (PIIIP), and procollagen type IV aminoterminal peptide (PIVP) levels in serum as well as transforming growth factor beta 1 (TGFbeta1) level in plasma were measured by radioimmunoassay (RIA) before and 6 months after the treatment. Doppler ultrasound recordings were obtained from all patients before and 6 months after the treatment to determine several parameters related to the left ventricular anatomy and function.. After 6 month of treatment, the mean blood pressure (MBP), PIIIP, PIVP, TGFbeta1, left ventricular mass index (LVMI), interventricular spectum dimension (IVSD), and left ventricular posterio wall dimension (LPWD) in the 2 groups were significantly lower than those before the treatment. TGFbeta1 decreased in the simvastatin and benazepril group compared with the benazepril group (P < 0.01). The ratio of early diastolic blood flow velocity of mitral valve (VE) and blood flow velocity of atrium systolic period (VA) in the 2 groups significantly increased after 6 months of treatment, and the ratio in the simvastatin and benazepril group was significantly higher than that in the enazepril group (P < 0.05).. Angiotension converting enzyme inhibitor combined with simvastatin is helpful to reduce the myocardial fibrosis and to improve the left ventricular hypertrophy and diastolic function in EH patients.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Drug Therapy, Combination; Female; Fibrosis; Humans; Hypertension; Male; Middle Aged; Myocardium; Simvastatin

Systolic hypertension is predominant among patients over 50 years of age, is a more important cardiovascular risk factor than diastolic blood pressure, and is more difficult to control than diastolic blood pressure. Consequently, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends combination therapy as first-line treatment for patients with stage 2 hypertension. In the Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) study, 24-hour ambulatory blood pressure monitoring was used to identify patients with systolic hypertension and to determine the impact of 8 weeks of treatment with either amlodipine besylate/benazepril HCl 5/20 mg combination therapy (n=149), amlodipine besylate 5 mg (n=146), or benazepril HCl 20 mg (n=148). Combination therapy was significantly more effective in reducing systolic blood pressure and pulse pressure than either monotherapy (p<0.0001). Significantly greater percentages of patients in the combination group compared with either monotherapy achieved blood pressure control (p<0.0001). Adverse events were low in all three treatment arms, with less peripheral edema in the combination group than in the amlodipine-treated group. The combination of amlodipine besylate/benazepril HCl given to patients with stage 2 systolic hypertension resulted in significantly greater reductions in blood pressure and pulse pressure than those seen with monotherapy and was at least as well tolerated as the separate components. This data supports the recommendation of the JNC 7 for the use of combination therapy in patients with stage 2 hypertension.

Topics: Aged; Amlodipine; Analysis of Variance; Antihypertensive Agents; Benzazepines; Blood Pressure Monitoring, Ambulatory; Chi-Square Distribution; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Systole; Treatment Outcome

This study examined the association between T1198C polymorphism of the angiotensinogen (AGT) gene and the blood pressure response to ACE inhibitors in a Chinese hypertensive cohort. After a 2-week single-blind placebo run-in period, benazepril (10-20 mg/day) or imidapril (5-10 mg/day) was administered for 6 weeks to 509 patients with mild-to-moderate essential hypertension. Polymerase chain reaction combined with restriction enzyme digestion was used to detect the polymorphism, and the patients were classified as having the TT, TC, or CC genotype. The achieved changes in systolic and diastolic blood pressure (SBP and DBP) were analyzed to determine their association with genotypes at the AGT gene locus. In the total 509 patients, the TT genotype was observed in 44 patients (8.7%), the TC genotype in 214 patients (42.0%), and the CC genotype in 251 patients (49.3%). The SBP reductions in patients with the TT genotype, TC genotype, and CC genotype were -15.3+/-12.7 mmHg, -14.0+/-12.7 mmHg, and -14.4+/-12.4 mmHg, respectively (p=0.809). The DBP reductions in patients with the TT genotype, TC genotype, and CC genotype were -8.5+/-8.1 mmHg, -8.3+/-7.5 mmHg, and -8.9+/-6.6 mmHg, respectively (p=0.638). There were no significant differences in the changes in SBP or DBP after treatment among the three genotype groups. In conclusion, these results suggest that the AGT genotype does not predict the blood pressure-lowering response to antihypertensive treatment with ACE inhibitors in Chinese hypertensive patients.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Antihypertensive Agents; Benzazepines; Blood Pressure; China; Double-Blind Method; Female; Humans; Hypertension; Imidazolidines; Male; Middle Aged; Polymorphism, Genetic

Angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers (CCBs) increase arterial compliance and decrease left ventricular mass in hypertensive patients. This study examined whether combined therapy has greater arterial and cardiac effects than doubled doses of the individual drugs.. This prospective, randomized, open-label study enrolled 106 patients aged >/=18 years with mild-to-moderate hypertension. Patients were randomized to 5 mg of amlodipine or 20 mg of benazepril for 2 weeks; then, depending on randomization assignment, they were force-titrated to 10 mg of amlodipine or 40 mg of benazepril monotherapy, or to combination amlodipine (5 mg) and benazepril (20 mg) treatment for 22 weeks. Arterial distensibility was assessed using the DynaPulse ambulatory system, and left ventricular mass was assessed by echocardiography.. Combination therapy (0.71% +/- 0.51% mL/mm Hg) increased arterial distensibility more than amlodipine (0.28% +/- 0.69% mL/mm Hg; P =.008) or benazepril (0.39% +/- 0.62% mL/mm Hg; P =.03) monotherapies. Left ventricular mass decreased more with combination treatment (65 +/- 56 g) than with amlodipine (28 +/- 4 g; P <.02); the difference from benazepril (42 +/- 50 g) was not significant.. Combined ACE inhibitor and CCB treatment was more efficacious than high doses of the individual agents in increasing arterial compliance and reducing left ventricular mass. These findings indicate that appropriately selected combinations of antihypertensive drugs might have enhanced cardioprotective effects.

Topics: Adult; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Calcium Channel Blockers; Drug Therapy, Combination; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Prospective Studies; Treatment Outcome; Vascular Capacitance; Vascular Resistance

The Seventh Report of the Joint National Committee (JNC 7) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends initial combination therapy for patients whose blood pressure (BP) is >20/10 mm Hg above goal. This study evaluated the efficacy and safety of initial combination therapy versus that of monotherapy in patients with stage 2 hypertension, who by definition meet the JNC 7 recommendation for initial combination antihypertensive therapy.. This multicenter, double-blind, 12-week study randomized 364 patients with stage 2 hypertension to fixed-dose combination therapy with amlodipine besylate/benazepril HCl (5/20 mg/d titrated to 10/20 mg/d) or amlodipine besylate monotherapy (5 mg/d titrated to 10 mg/d).. Significantly more patients randomized to combination therapy (74.2%) compared with those randomized to monotherapy (53.9%; P <.0001) achieved the primary end point (reductions in systolic BP > or =25 mm Hg, if baseline systolic BP was <180 mm Hg, or > or =32 mm Hg, if baseline systolic BP was > or =180 mm Hg). Significantly more patients randomized to combination therapy compared with monotherapy attained BP goals of <140/90 mm Hg (61.0% v 43.3%; P =.0007) and < or =130/85 mm Hg (35.7% v 19.1%; P =.0004). Among patients with baseline systolic BP > or =180 mm Hg, combination therapy resulted in significantly greater reductions in systolic BP compared with monotherapy (-42.3 v -30.4 mm Hg; P =.001). More than 90% of patients in each group were titrated to the higher dose. Both treatments were well tolerated.. Combination therapy was well tolerated and resulted in significantly greater BP reductions and attainment of BP goals compared with monotherapy in patients with stage 2 hypertension. This evidence supports the recommendation of combination therapy as first-line treatment in stage 2 hypertension.

Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Calcium Channel Blockers; Diastole; Dose-Response Relationship, Drug; Double-Blind Method; Drug Evaluation; Drug Therapy, Combination; Edema; Female; Humans; Hypertension; Male; Middle Aged; Severity of Illness Index; Systole; Treatment Outcome

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.. 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.. 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.. 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.

Topics: Adult; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Diastole; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Heart Rate; Humans; Hypertension; Male; Systole; Time Factors; Treatment Outcome; United States

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.

Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Ankle; Benzazepines; Calcium Channel Blockers; Cross-Over Studies; Diagnostic Techniques, Cardiovascular; Double-Blind Method; Drug Therapy, Combination; Edema; Female; Humans; Hydrostatic Pressure; Hypertension; Male; Middle Aged

The correlation of the angiotensin-converting enzyme insertion/deletion polymorphism with essential hypertension shown in previous studies is controversial, and the responses of hypertensive patients with different angiotensin-converting enzyme genotypes to treatment with an angiotensin-converting enzyme inhibitor merits investigation.. Eighty-nine patients with essential hypertension and 102 normotensive subjects were included in this study. All subjects were genotyped by polymerase chain reaction for the insertion/deletion polymorphism of the angiotensin-converting enzyme gene. Blood pressure was measured before and after taking Benazepril 10 mg, once daily, for 2 months.. The genotype and allele frequencies were similar (chi(2) = 0.64, P =.73; chi(2) = 0.36, P =.55, respectively). The reduction of both systolic and diastolic blood pressure in the DD genotype was significantly greater than in the II genotype (10.13 +/- 4.91 vs 5.37 +/- 2.79, P <.01; 7.47 +/- 3.50 vs 4.71 +/- 2.40, P <.05, respectively).. No significant association of angiotensin-converting enzyme gene polymorphism with essential hypertension was found. Angiotensin-converting enzyme gene polymorphism might be related to the antihypertensive response to an angiotensin-converting enzyme inhibitor in hypertensive patients.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Female; Genotype; Humans; Hypertension; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic

To evaluate the effects of valsartan (Val) with or without benazepril (Ben) on blood pressure and plasma levels of angiotensin (Ang II) and digoxin-immunoreactive factors (endoxin) in patients with essential hypertension.. Ninety patients with essential hypertension were randomly divided into 3 groups (n=30 per group): Ben group (Ben 10 mg/d, po); Val group (Val 80 mg/d, po); combination drug therapy group (Val 80 mg/d+Ben 10 mg/d, po); all patients were treated for 12 weeks. Age and sex-matched 20 normal subjects were served as control group.. The levels of plasma endoxin and Ang II in patients with essential hypertension were remarkably higher than those in normal subjects. The levels of plasma Ang II and endoxin were all obvious positive correlation with systolic blood pressure (SBP) and diastolic blood pressure (DBP) (Ang II: r=0.5151, 0.7978; endoxin: r=0.4706, 0.7274, respectively). Within 6 weeks of drug intervene, SBP and DBP were remarkably decreased in 3 groups. After 6 weeks, SBP and DBP were continuously decreased in Ben group and Val+Ben group, but not in Val group. Level of plasma Ang II was remarkably decreased as SBP and DBP decreased in Ben group and Val+Ben group; level of plasma Ang II was remarkably increased in Val group.. Val with or without Ben remarkably decreased SBP and DBP in patients with essential hypertension within 6 weeks. Antihypertensive efficacy was weakened after long-term use of Val alone. The antihypertensive effect of Val+Ben group was the most remarkable among 3 groups and could avoid the side effects of high plasma Ang II.

Topics: Adult; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Cardenolides; Digoxin; Female; Humans; Hypertension; Male; Middle Aged; Saponins; Tetrazoles; Valine; Valsartan

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.. 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.. 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).. 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.

Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Calcium Channel Blockers; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Fibrinolysis; Humans; Hypertension; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Single-Blind Method; Tissue Plasminogen Activator

Hypertension is common in older adults (aged > or =65 years). Treatment frequently requires multiple medications and can be expensive.. 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.. 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.. 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.. 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.

Topics: Aged; Aged, 80 and over; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Calcium Channel Blockers; Cost Savings; Drug Combinations; Female; Humans; Hypertension; Long-Term Care; Male; Middle Aged; Pilot Projects; Quality Assurance, Health Care; Treatment Outcome

The aim of this study was to investigate the relationship between polymorphism of the anglotensin-converting enzyme (ACE) gene and the blood pressure response to ACE inhibition in a hypertensive cohort. Imidapril (5-10 mg/day) or benazepril (10-20 mg/day) was administered for 6 weeks to 517 essential hypertensives. ACE gene polymorphism was examined by the polymerase chain reaction (PCR) method and the patients were classified as having the 190-bp deletion homozygous (DD) genotype, the 490-bp insertion homozygous (II) genotype, or the 490-bp insertion, 190-bp deletion heterozygous (ID) genotype. The achieved change in systolic and diastolic blood pressure (SBP and DBP) was analyzed for association with genotypes at the ACE gene locus. The DD genotype was observed in 132 patients (25.5%), the ID genotype in 255 patients (49.3%), and the II genotype in 130 patients (25.2%). The SBP reductions in the patients with the DD genotype, II genotype, and ID genotype were -14.5 +/- 12.7 mmHg, -14.3 +/- 13.1 mmHg and -14.0 +/- 12.2 mmHg, respectively (p = 0.94). The DBP reductions in the patients with the DD genotype, II genotype, and ID genotype were -8.7 +/- 7.4 mmHg, -8.7 +/- 7.7 mmHg and -8.5 +/- 6.7 mmHg, respectively (p = 0.96). There was no significant association between the ACE gene polymorphisms and the response to ACE inhibition. These results suggest that ACE genotype does not predict the blood pressure-lowering response to antihypertensive treatment with ACE inhibition.

Topics: Aged; Alleles; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Data Interpretation, Statistical; DNA; DNA Primers; Double-Blind Method; Female; Gene Frequency; Humans; Hypertension; Imidazoles; Imidazolidines; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Reverse Transcriptase Polymerase Chain Reaction; Sex Characteristics

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.. 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.. 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.. Fixed-dose combination antihypertensive agent amlodipine/benazepril was safe and effective for patients who experienced either inadequate BP control or edema with amlodipine monotherapy.

Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Calcium Channel Blockers; Drug Combinations; Edema; Female; Humans; Hypertension; Male; Middle Aged; Treatment Outcome

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.. 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.. 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.. 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).. 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.

Topics: Administration, Oral; Aged; Amlodipine; Antihypertensive Agents; Benzazepines; Captopril; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged

To make a cost-effectiveness analysis (CEA) comprehensive evaluation for 4 hypotensive drugs, by observing the effects of drugs on blood pressure lowering, symptom improving, and adverse effect and quality of life (QOL) influencing.. Two hundred and ninety-two patients with mild to moderate hypertension were divided into 4 groups at random and treated with compound Lingjiao Jiangya Pill, benazepril, amlodipine and indapamide respectively with a therapeutic course of 6 weeks. QOL was measured with FS-36 questionnaire and efficacy policy model was applied for comprehensive evaluation of CEA.. Through CEA a comprehensive evaluation was made in order as follows: indapamide 3.65 which was the best, and then Lingjiao Jiangya Pill 3.55, amlodipine 2.90 and benazepril 2.35.. The 4 drugs can not only lower blood pressure but also improve clinical symptoms with less adverse effect. It is of great practical significance to evaluate hypotensive drugs by combining QOL appraisal. The position of Lingjiao Jiangya Pill in CEA order suggests that more attention should be paid to herbal hypotensive drugs.

Topics: Adult; Aged; Aged, 80 and over; Amlodipine; Antihypertensive Agents; Benzazepines; Cost-Benefit Analysis; Drugs, Chinese Herbal; Female; Humans; Hypertension; Indapamide; Male; Middle Aged; Phytotherapy; Quality of Life

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.. Randomised, double-blind, placebo-controlled, parallel-group, multicentre trial.. Twenty-two clinical centres, including private practice groups and academic research clinics.. 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.. 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.. 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.

Topics: Adult; Aged; Aged, 80 and over; Amlodipine; Antihypertensive Agents; Benzazepines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Treatment Outcome

Previous clinical trials have demonstrated the important influence of ethnicity and dietary salt on the antihypertensive efficacy of drugs that block the renin angiotensin system. Angiotensin II receptor blockers are a new therapeutic entity that have not been widely studied in African American hypertensives, either alone, or in combination with other therapies such as diuretics or angiotensin converting enzyme inhibitors. We performed a pilot, prospective, open label, randomized design clinical trial to evaluate the effects of the angiotensin II receptor blocker valsartan (160 mg once a day) on systolic and diastolic blood pressure in hypertensive African Americans (n = 88) on a low salt (100 mEq Na+/day) for 2 weeks and the same diet supplemented by 100 mEq Na+ for 4 weeks. After this evaluation, while continuing the Na+ supplementation, patients were randomized to valsartan 320 mg/day (n = 28), or the addition of hydrochlorothiazide (HCTZ) 12.5 mg/day (n = 30), or benazepril 20 mg/day to the valsartan 160 mg/day for an additional 6 weeks. Valsartan (160 mg/day) lowered blood pressure significantly in African American patients on both low salt (-6.4/-4.8 mm Hg: P < .001) and a high salt diet (-4.9/-3.8 mm Hg: P = .01). The high salt diet attenuated the antihypertensive effect slightly (1.6/1.3 mm Hg, P = not significant). When comparing the efficacy of the three randomized therapeutic regimens while on the Na+ supplement, the valsartan 160 mg/HCTZ 12.5 mg was the most effective therapy with an incremental reduction in blood pressure of -10.5/-6.9 mm Hg (P < .01), compared to valsartan 160 mg/day alone. Doubling the dose of valsartan to 320 mg incrementally lowered blood pressure by -3.8/-3.3 mm Hg (P = not significant). The least effective approach was adding benazepril 20 mg/day to valsartan 160 mg/day with no incremental reduction in systolic blood pressure and diastolic blood pressure reduction of only 1.7 mm Hg (P = not significant). We conclude that in our open label pilot study, the antihypertensive activity of valsartan is not significantly attenuated by supplemented salt diet in hypertensive African Americans. Moreover, adding a low dose of HCTZ appears to be the most effective strategy in enhancing the antihypertensive activity of this angiotensin II receptor blocker in contrast to either doubling the dose or adding an angiotensin converting enzyme inhibitor.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Black People; Diuretics; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Pilot Projects; Prospective Studies; Sodium Chloride Symporter Inhibitors; Sodium, Dietary; Tetrazoles; Valine; Valsartan

To investigate the beneficial effects of cilnidipine, a calcium channel blocker that shows high selectivity for N-type receptors, on the progression of chronic renal insufficiency, we compared the efficacy of cilnidipine to that of benazepril, an angiotensin-converting enzyme (ACE) inhibitor with known renal protective effects, in a one-year trial evaluating hypertensive control, serum creatinine, and albuminuria in a cohort of patients. Given the seeming importance of the etiology of chronic renal insufficiency in determining drug efficacy, we limited our study to 20 patients with a single common condition, benign nephrosclerosis. The average age of the patients was 62+/-4 years old. The changes in systolic and diastolic blood pressure over the course of the study year revealed a similar reduction with cilnidipine and benazepril. Both cilnidipine and benazepril induced similar reductions in systolic and diastolic blood pressure over the course of the study year. The baseline levels of serum creatinine were 1.40+/-0.2 mg/dl and urinary excretion of albumin was 168+/-10 mg daily. The levels of serum creatinine were not significantly changed throughout the study in either group, although the levels of urinary excretion of albumin were significantly decreased in both groups. There were no significant differences in either of these values between the two groups. In conclusion, both cilnidipine and benazepril equally and effectively reduced blood pressure and albuminuria in hypertensive patients with benign nephrosclerosis in a one-year trial.

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Calcium Channel Blockers; Cohort Studies; Creatinine; Dihydropyridines; Female; Glomerular Filtration Rate; Humans; Hypertension; Male; Middle Aged; Nephrosclerosis; Proteinuria

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.. A total of 327 patients were included in the trial and 153 patients (46%) had their diastolic BP

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Diuretics; Drug Combinations; Drug Resistance; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Sodium Chloride Symporter Inhibitors; Tetrazoles; Valine; Valsartan

Several experimental and clinical studies indicate that the renin system may play a pivotal role in progressing renal disease. The combination of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker could provide a higher degree of blockade of the renin-angiotensin system than either agent alone. Such enhanced suppression might be of benefit for patients exhibiting a progressive decline in renal function because of chronic renal disease.. A pilot multinational, multicentre, randomized, active-controlled, parallel group open-label study has been conducted in a group of patients with progressive chronic renal failure (creatinine clearance 20-45 ml/min) either with or without proteinuria and hypertension. The primary aim of the study was to investigate the safety and tolerability of the combination of valsartan and benazepril. Patients were randomly assigned to one of three groups: group 1 received valsartan 160 mg once daily (n = 22); group 2 received valsartan 80 mg once daily plus benazepril 5 or 10 mg once daily (n = 42); group 3 received valsartan 160 mg once daily plus benazepril 5 or 10 mg once daily (n = 44). The study lasted for 5 weeks, and in groups 2 and 3 benazepril was added on top of valsartan after the first week of therapy with the angiotensin receptor blocker.. Serum creatinine increased in all three groups (mean change within a group: 11 micromol/l in group 1, P= 0.045; 9 micromol/l in group 2, P= 0.030; 15 micromol/l in group 3, P= 0.0006). Serum potassium also increased in all three groups of patients (mean change within a group: 0.28 mmol/l in group 1, P= 0.28; 0.48 mmol/l in group 2, P= 0.0008; 0.36 mmol/l in group 3, P= 0.02). After 5 weeks of treatment, the largest decrease in blood pressure was observed in group 3 (the mean change from baseline in seated diastolic blood pressure (SDBP) and seated systolic blood pressure (SSBP), respectively, were: -2.0 and -11.5 mmHg in group 1; -7.6 and -15.4 mmHg in group 2; -12.6 and -21.6 mmHg in group 3). In addition, both combination treatments resulted in the reduction of proteinuria. The total number of patients with adverse experiences were 10 (45.5%), 14 (33.3%) and 11 (25%) in groups 1,2 and 3, respectively. In six patients (5.6%) therapy was discontinued as a result of adverse experiences. Only one patient in each of the combined therapy groups withdrew from the study because of hyperkalaemia and no patients were forced to withdraw because of an increase in serum creatinine, acute renal failure or hospitalization.. These results indicate that short-term combination of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker is safe and well tolerated in patients with moderate chronic renal failure.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Creatinine; Drug Combinations; Female; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Pilot Projects; Potassium; Proteinuria; Safety; Tetrazoles; Valine; Valsartan

The study was designed to assess the antihypertensive effect of combined angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor (AT1) antagonism in patients with essential hypertension. Twenty patients with uncontrolled ambulatory diastolic blood pressure (BP) after 6 weeks of ACE inhibitor monotherapy (benazepril, 20 mg, o.d.) were randomized to receive double-blind valsartan, 80 mg, o.d. (AT1 antagonist) or matching placebo for 5 weeks while continuing to receive background benazepril. Then patients crossed over to the alternative regimen for a second 5-week period. The 24-h ambulatory BP was monitored on the final day of the benazepril monotherapy period and on the final day of each double-blind treatment period. Valsartan added to benazepril produced a significant antihypertensive effect with a benefit over placebo of 6.5 +/- 12.6/4.5 +/- 8.0 mm Hg (systolic/diastolic) for average awake ambulatory BP (p < 0.05), 7.1 +/- 9.4/5.6 +/- 6.5 mm Hg for asleep BP (p < 0.01), and 6.8 +/- 9.7/4.9 +/- 6.8 mm Hg for average 24-h ambulatory BP (p < 0.01). Pulse rate was unaffected. Plasma active renin was higher on the benazepril-valsartan combination compared with benazepril-placebo (p < 0.05). There was no change in routine biochemical variables when valsartan was added to benazepril. Six patients reported mild dizziness or fatigue (three also with placebo). These data suggest that in hypertensive patients uncontrolled with an ACE inhibitor, the addition of an AT1 antagonist provides a powerful and safe antihypertensive drug combination.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Cross-Over Studies; Diastole; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Humans; Hypertension; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Systole; Tetrazoles; Time Factors; Valine; Valsartan

The present 2 multicenter studies were designed to evaluate whether patients with essential hypertension derived equal benefits from use of combination therapy with a calcium antagonist and angiotensin-converting enzyme (ACE) inhibitor as from doubling the dose of the calcium antagonist. After a 2-week washout and a 2-week single-blind placebo run-in period, a total of 1,390 patients were treated with either nifedipine 30 mg (study 1) or amlodipine 5 mg (study 2) once daily for 4 weeks. The 1,079 patients whose diastolic blood pressure remained between 95 and 115 mm Hg were randomized to 8 weeks of double-blind therapy with amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg/ benazepril 20 mg, nifedipine 30 mg or nifedipine 60 mg (study 1), and amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg/benazepril 20 mg, amlodipine 5 mg or amlodipine 10 mg (study 2). Both doses of the calcium antagonist/ACE inhibitor combination therapy lowered diastolic pressure as much as the high dose and significantly better than the lower dose of calcium antagonist monotherapy (with either nifedipine or amlodipine). However, 15% of patients in the nifedipine high-dose monotherapy group and 24% in the amlodipine high-dose monotherapy group presented with some form of edema. In contrast, the incidence of edema was similar for patients treated with both combination therapy and low-dose calcium antagonists. Thus, combination therapy with a calcium antagonist and an ACE inhibitor provides blood pressure control equal to that of high-dose calcium antagonist monotherapy but with significantly fewer dose-dependent adverse experiences such as vasodilatory edema. Inc.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Calcium Channel Blockers; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Nifedipine; Single-Blind Method

The relative importance of hypertension in the progression of renal failure is well understood. Recently, several studies have provided evidence that antihypertensive therapy enhances renal survival. However, the specific antihypertensive drug regimens that are most effective in generating such long-term effects remain controversial.. Forty-nine hypertensive IgA nephropathy (IgAN) patients (39 +/- 7 years old, serum creatinine 1.1 +/- 0.2 mg/dl) with proteinuria received antihypertensive therapy with angiotensin-converting enzyme inhibitors (ACEi: 2.5-10 mg of benazapril daily) and calcium channel blockers (CCBs: 2.5-10 mg amlodipine daily) for 3 years. The patients' blood pressures in group one were controlled below 140/85 mmHg by increases in their first drug dose or by addition of the second drug in group 1. Blood pressures for patients in group 2 were controlled using the same two options, except to levels below 130/70 mmHg. Patients within the two groups were selected and controlled with regard to sex, age, and serum creatinine. The renal protective effects of each protocol were evaluated in terms of reductions in creatinine clearance. After 3 years of the above outlined blood pressure control regimens, the reductions in creatinine clearance were compared.. Creatinine clearances decreased in group 1 patients (from 85.7 +/- 2.4 ml/min to 72.9 +/- 2.4 ml/min, p < 0.05). On the other hand, creatinine clearance remained essentially unchanged for patients in group 2 (from 87.2 +/-4.7 ml/min to 85.9 +/- 5.9 ml/min). Although creatinine clearance in both groups was almost the same at the start of study, there was a significant difference between them by the conclusion of the study (p < 0.05). Proteinuria and hematuria did not change significantly throughout the study and there were no significant differences in these respects between these two corresponding groups. There were no significant differences between the groups with reference to side-effects or complications.. These data provide evidence that reducing blood pressure has protective renal effects in cases of mild renal insufficiency with hypertension in IgA nephropathy.

Topics: Adult; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Calcium Channel Blockers; Creatinine; Drug Administration Schedule; Female; Follow-Up Studies; Glomerulonephritis, IGA; Humans; Hypertension; Male

To evaluate the efficacy and safety of Benazepril used among the essential hypertensives.. 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.. 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.. Results showed that Benazepril had good efficacy and safety for the essential hypertension patients in a long-term observation.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; China; Cough; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Product Surveillance, Postmarketing

The aim of the study was to evaluate in general practice, in a large and unselected population of patients, the efficacy and safety of benazepril associated or not with hydrochlorothiazide (HCTZ) and to identify clinical and demographic predictive factors of antihypertensive efficacy. In this open uncontrolled study, 16,987 patients with mild to moderate hypertension were included by 5350 GPs. They received benazepril (BNZ) 10 mg once daily for 8 weeks. If sitting DBP remained > 90 mmHg after 4 weeks, HCTZ 12.5 mg once a day was then added for the last 4 weeks.. In the intent to treat analysis, 54.5% of patients, after 4 weeks, and 80.6% of patients after 8 weeks, were controlled (DBP < 90 mmHg). Mean sitting DBP decreased from 100.5 +/- 5.5 mmHg (baseline) to 86.7 +/- 7.5 mmHg after 4 weeks and to 82.5 +/- 6.5 mmHg after 8 weeks. Mean SBP decreased from 169.5 +/- 13.1 mmHg to 150.5 +/- 12.5 mmHg after 4 weeks and to 145.0 +/- 10.9 mmHg after 8 weeks. Of the 16,900 patients included in the safety analysis, 853 (5.0%) dropped out of the study, 504 (3.0%) for adverse events (AE). The most frequent AE were: cough (3.5%), headache (0.9%), dizziness (0.8%), asthenia (0.6%) and nausea (0.5%). 13 deaths were observed during the study, mainly due to stroke or cancer. Six cases of raised serum creatinine level, 3 cases of angio-oedema and 2 cases of hepatitis were also reported. After 8 weeks of treatment, the main predictors of therapeutic response (DBP) were: recently discovered hypertension (86.3% of controlled DBP), regular exercise (85.5%) and age < 50 years (84.6%). Conversely: obesity, diabetes mellitus (77.9%), previously treated with several drugs (75.2%) and initial DBP > or = 105 mmHg (74.5%) were not predictive. Predictive factors emerging from logistic regression were : baseline DBP (< 105 mmHg), history of hypertension, body mass index, initial treatment of hypertension (no treatment--one drug--several drugs) and age.. This large-scale study confirms, the antihypertensive efficacy and good tolerability of benazepril alone or associated with hydrochlorothiazide in general practice.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Female; Humans; Hypertension; Male; Middle Aged; Predictive Value of Tests; Severity of Illness Index

To assess the comparative effects of benazepril and nitrendipine monotherapies on left ventricular mass index (LVMI) in hypertensive patients with echocardiographically determined left ventricular hypertrophy, patients with diastolic blood pressure (BP) > or = 100 mm Hg were randomized to benazepril, 10 mg, or nitrendipine, 20 mg, both given once or twice daily. After 4 weeks, only the responders (diastolic BP <90 mm Hg) entered a 5-month maintenance period. At baseline, and after 3 and 6 months, LVMI was blindly estimated by means of magnetic resonance imaging (MRI) and, for comparison, by means of echocardiography. Of the 50 randomized patients, three were excluded from the study as nonresponders after 4 weeks; moreover, two patients taking benazepril and one taking nitrendipine discontinued the treatment after 2 months for adverse effects. Both monotherapies reduced systolic and diastolic BP to a similar extent. After 3 months, MRI-estimated LVMI decreased by 21.5 g/m2 in the benazepril and 8.8 g/m2 in the nitrendipine group, with an adjusted mean difference between the two groups of 11.1 g/m2 (95% CI, 7.3-14.8 g/m2; p = 0.0001). After 6 months, it decreased by 23.6 g/m2 and 10.0 g/m2, respectively, with an adjusted mean difference of 11.3 g/m2 (95% CI, 7.5-15.5; p = 0.0001) in favor of benazepril. In conclusion, despite a similar antihypertensive effect, benazepril led to a greater reduction in MRI-measured LVMI than did nitrendipine (-16.2% vs. -7.2%) in hypertensive patients with left ventricular hypertrophy.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Calcium Channel Blockers; Echocardiography; Female; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Male; Middle Aged; Nitrendipine; Prospective Studies; Ventricular Function, Left

The aim of this study was to determine whether angiotensin-converting enzyme inhibitor administration improves the endothelial function of patients with previously untreated essential hypertension. Using high-resolution ultrasonography, we measured the arteria brachialis diameter at rest, during reactive hyperemia (endothelium-dependent flow-mediated dilatation [FMD]), and after sublingual nitroglycerin (endothelium-independent dilatator). Twenty-one previously untreated hypertensive patients participated in the study (13 men, 8 women; mean age, 39.1 +/- 15 years). In the 21 patients, the basal FMD was 5.02% +/- 4.1%. Two hours after the first 10-mg benazepril dose, the FMD was 6.67% +/- 3.9%, and after 1 month of daily 10-mg benazepril administration, the FMD was 5.59% +/- 2.9%. These changes were not significant compared with the baseline value. Nine patients had relatively normal FMD (>5%), whereas the other 12 patients had abnormal FMD (<5%) at baseline. In the latter group, the first 10 mg benazepril produced significant improvement in FMD, from 2.4% +/- 2.5% to 5.08% +/- 2.4% (P < 0.05), but 10 mg benazepril daily for 1 month resulted in no further improvement (4.78% +/- 2.7%) compared with the acute effect. No difference was found between groups with regard to age, gender, blood pressure, blood lipids, and basal arteria brachialis diameter. The previously untreated patients with essential hypertension have endothelial dysfunction, but individual differences were found. The angiotensin-converting enzyme inhibitor treatment improves endothelial function only in those patients who had endothelial dysfunction before the treatment.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Brachial Artery; Endothelium, Vascular; Female; Humans; Hypertension; Male; Ultrasonography; Vascular Resistance

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.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Female; Humans; Hypertension; Male; Middle Aged

The antihypertensive efficacy and tolerability of a fixed combination of benazepril (10 mg) and low-dose amlodipine (2.5 mg) were assessed in 24 patients (mean age, 43.9 years) with uncomplicated mild to moderate essential hypertension [supine diastolic blood pressure (DBP) > or = 95 and < or = 120 mm Hg)]. After 2 weeks of washout taking placebo, patients were randomized to receive the fixed combination or placebo, both administered once daily for 3 weeks, according to a double-blind, crossover design. Patients were checked at the end of the washout period and every 3 weeks thereafter. At each visit, 24-h ambulatory BP monitoring (ABPM) was performed by a noninvasive device (Spacelabs 90207); casual BP (by mercury sphygmomanometer), heart rate (HR), and body weight also were measured. The fixed combination significantly reduced systolic (SBP) and DBP values throughout the 24 h as compared with placebo, without affecting the normal BP circadian variability. The antihypertensive effect of the fixed combination could be observed to a similar extent during the day and night and was still significant 24 h after dosing. HR and body weight were not affected by the treatment. The fixed combination of benazepril 10 mg/amlodipine 2.5 mg was well tolerated, and no patient withdrew from the study because of side effects.

Topics: Adult; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Double-Blind Method; Drug Combinations; Humans; Hypertension; Male; Middle Aged

In a multicenter, randomized, double-blind, placebo-controlled study, we evaluated the efficacy and tolerability of the combination of benazepril, 10 mg, and amlodipine, 2.5 or 5 mg once daily, compared with benazepril, 10 mg, monotherapy in patients with hypertension inadequately controlled with angiotensin-converting enzyme (ACE)-inhibitor monotherapy. After a 2-week placebo and 4-week single-blind benazepril, 10 mg once daily, run-in period, 448 patients, 213 men and 235 women, aged 24-73 years (mean, 55 years), with mean diastolic blood pressure (DBP) > or =95 and < or =120 mm Hg at the end of the benazepril run-in period, were randomized to receive one of the following treatments once daily for 8 weeks: (a) benazepril, 10 mg, plus placebo (BZ10); (b) benazepril, 10 mg, plus amlodipine, 2.5 mg (BZ10/AML2.5); or (c) benazepril, 10 mg, plus amlodipine, 5 mg (BZ10/AML5). Before the patients were admitted to the trial, at the end of the placebo run-in and the benazepril run-in period and at the end of weeks 4 and 8 of the treatment period, sitting and standing blood pressure (BP), heart rate (HR), and body weight were measured 22-26 h after the intake of the trial medication. Both BZ10/AML2.5 and BZ10/AML5 combinations showed better antihypertensive activity than did BZ10 monotherapy at the terminal visit as demonstrated by (a) the 24-h postdosing sitting and standing systolic BP (SBP) and DBP values, which were statistically lower with combination therapy than with BZ10; (b) the success rate, which was statistically higher with both the combinations (69.2% in the BZ10/AML2.5 and 65.8% in the BZ10/AML5 group) compared with the BZ10 group (40.5%). The tolerability was good in the three treatment groups. No significant abnormal laboratory data were detected. There was no difference in efficacy and safety/tolerability between the BZ10/AML2.5 and BZ10/AML5 groups.

Topics: Adolescent; Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Placebos

To assess the efficacy and safety of several combinations of benazepril, an angiotensin-converting enzyme inhibitor, and hydrochlorothiazide, as compared with placebo, in the treatment of patients with essential hypertension.. A 6-week, randomized, double-blind, parallel study conducted at 24 centers. A placebo run-in period of 1 to 4 weeks preceded the double-blind phase.. Male and female outpatients, aged 18 years and older, were eligible to participate if their sitting diastolic blood pressure was between 95 and 114 mm Hg at the last two consecutive visits during the placebo phase. Among the 334 patients who entered the double-blind phase, 17% were aged 65 years or older and 26% were black. Eleven patients withdrew because of adverse experiences, including two patients receiving placebo.. Patients received placebo; benazepril, 20 mg; hydrochlorothiazide, 25 mg; or combination therapy with benazepril/hydrochlorothiazide, 5/6.25 mg, 10/12.5 mg, 20/25 mg, 20/6.25 mg, or 5/25 mg, once daily for 6 weeks.. The mean change from baseline in sitting diastolic blood pressure at end point (last postrandomization measurement carried forward) in the double-blind phase. Combination therapy with benazepril/hydrochlorothiazide, 20/25 mg, was compared with benazepril, 20 mg alone, and hydrochlorothiazide, 25 mg alone. Sitting systolic blood pressure and the effect of race and age on treatment efficacy were also evaluated.. Compared with placebo, all benazepril/hydrochlorothiazide combinations produced statistically significant reductions from baseline in sitting diastolic and systolic blood pressures at study end point. In the benazepril/hydrochlorothiazide, 20/25 mg, group, the adjusted mean changes in sitting diastolic blood pressure at end point were statistically significantly greater than those in the monotherapy treatment groups (benazepril, 20 mg, P < or = .05; hydrochlorothiazide, 25 mg, P < or = .001) alone. All therapies were generally well tolerated. Decreases in mean serum potassium level with hydrochlorothiazide monotherapy were reduced or eliminated with combination therapy.. Benazepril in combination with hydrochlorothiazide, including a low-dose combination of 5/6.25 mg, is effective in reducing sitting diastolic and systolic blood pressure in patients with hypertension.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Treatment Outcome

The effects of the treatment with benazepril (BEN) on blood pressure and renal function have been evaluated in nine adult patients affected by mild to moderate hypertension. BEN was administered orally, at a single daily dose of 10 mg for four weeks. BEN induced a clinically significant decrease in blood pressure, from a mean basal value of 155/98 mm Hg (+/- 15/7 SD) to 146/92 (+/- 12/9) after seven days of therapy and 139/88 (+/- 11/10) after 28 days in supine position and from 152/104 (+/- 17/6) to 144/97 (+/- 14/6) after seven days and 145/99 (+/- 16/9) after 28 days in a standing position. Plasma urea, creatinine, uric acid and their clearances as well as urine enzymes (GGT, ALP, LDH) remained stable throughout the duration of the therapy. GFR showed a modest increase, from 61.3 +/- 13.2 ml/min to 65.3 +/- 18.3 ERPF showed a slightly more evident increase, from 246.7 +/- 68.1 ml/min to 276.9 +/- 75.6. Plasma levels of glucose, cholesterol and triglycerides were not influenced by BEN. Plasma potassium increased from 4.0 +/- 0.3 to 4.4 +/- 0.5 mEq/liter. The results of this study indicate that BEN is a safe and effective antihypertensive agent that does not cause any adverse renal or metabolic effects.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Female; Humans; Hypertension; Kidney; Male; Middle Aged

Salt intake, and the sensitivity of blood pressure (BP) to excessive salt intake is thought to contribute to the pathogenesis of essential hypertension in some patients. This study was designed to ascertain whether salt sensitivity of BP is a determinant of BP and renal vascular responsiveness to angiotensin converting enzyme (ACE) inhibition. In 24 patients with essential hypertension, ranging in age from 30 to 68 years, renin status, renal hemodynamics, and sensitivity of BP to steady state changes in salt intake were assessed. Twenty-four hour ambulatory BP monitoring (ABPM) was employed to measure baseline BP and BP response to 4 weeks' treatment with benazepril at 20 or 40 mg/day. Benazepril induced a highly-significant reduction in BP (P < .001) and increase in renal plasma flow (530 +/- 17 to 580 +/- 19 mL/min/1.73 m2; P < .001). Systolic BP fell from 143 +/- 2 to 129 +/- 2 mm Hg (P < .001), and diastolic BP fell from 91 +/- 1.6 to 80 +/- 2 mm Hg (P < .001). The magnitude of the BP and renal vascular response to ACE inhibition was not influenced by the sensitivity of BP to salt intake. In a multivariate analysis neither body mass index nor age influenced the BP response to ACE inhibition or the relationships between salt intake and a BP response to ACE inhibition. We conclude that the factors that influence sensitivity of BP to salt intake do not influence the systemic or renal hemodynamic response to ACE inhibition.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Female; Humans; Hypertension; Male; Middle Aged; Renin; Sodium; Sodium Chloride, Dietary

Diabetic nephropathy is the most frequent cause of chronic renal failure. The onset of microalbuminuria in patients with diabetes mellitus, which seems to be related to blood pressure and the control of glycemia, is predictive of the development of true proteinuria. This multicenter, single-blind, randomized study examined the effects of benazepril and nicardipine on overnight microalbuminuria in 57 normotensive and 46 hypertensive diabetic patients. At the end of a 3-month placebo run-in period, the patients were stratified on the basis of the presence or absence of arterial hypertension and, within each stratum, randomized to receive one daily tablet of 10 mg benazepril or one tablet of 20 mg nicardipine twice daily for 6 months. Renal hemodynamics was investigated in 25 patients. Both drugs decreased overnight microalbuminuria throughout the study period, but benazepril was more effective than nicardipine (p = 0.025); in the patients with hypertension, both drugs led to a similar marked reduction in systolic and diastolic blood pressure. This study shows that benazepril was more effective than nicardipine in reducing overnight microalbuminuria in patients with diabetes mellitus, independently of their antihypertensive properties.

Topics: Adult; Aged; Albuminuria; Antihypertensive Agents; Benzazepines; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Kidney; Male; Middle Aged; Nicardipine; Single-Blind Method

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Drug Costs; Drug Utilization Review; Enalapril; Formularies, Hospital as Topic; Georgia; Humans; Hypertension; Retrospective Studies

The aim of the study was to assess the influence of angiotensin converting enzyme inhibitors (ACEI) on zinc metabolism.. Thirty one patients (pts) with essential hypertension (EH) were divided into two groups: 1. 16 pts. 6 females (F) and 10 males (M) (age 46.5 +/- 7) who were treated with benazepril (nonsulphydryl ACEI). 2. 15 pts, 6F and 9M (age 45.9 +/- 10.7) receiving captopril (sulphdryl ACEI). Trial was randomized, double-blind. The dose of 10 mg of benazepril administered once daily was compared with 50 mg of captopril once daily. If after 4 weeks of treatment the blood pressure (BP) was adequately controlled (DBP < or = 90 mmHg)), the same treatment was continued for further 4 weeks. In pts with DBP > 90 mmHg after 4 weeks, the dosage of trial medication was doubled and continued for further 4 weeks. Erythrocyte (ZnE) and serum (ZnS) zinc as well as 24 hour urinary zinc excretion (ZnU) and glomerular filtration rate were assessed before starting treatment and after 4 and 8 weeks of ACEI therapy.. ZnS significantly lowered and ZnU increased during ACEI therapy whereas ZnE did not change. Up to 4 weeks there were no statistical differences between captopril and benazepril regarding their influence on zinc metabolism. After 8 weeks of therapy ZnS decreased more significantly in captopril group (p < 0.01). Glomerular filtration rate did not significantly change during ACEI therapy.. ACEI therapy may influence zinc metabolism.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Captopril; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hypertension; Male; Middle Aged; Zinc

Changes in arterial hypertension, heart rate and adrenocortical hormones (11-OCS, aldosteron, progestins) in the blood and 24-h urine were followed up in the course of 24-week use of angiotensin-converting enzyme inhibitor benazepril (10-20 mg once a day) in 24 patients with mild and moderate essential hypertension (EH) included in a placebo-controlled randomized study. A 2 and 24-week antihypertensive response was achieved in 75 and 71% of patients, respectively. 24-h urinary excretion of corticosteroids before the treatment was increased. After the treatment benazepril reduced excretion of 11-OCS by 42%, but not of aldosteron the levels of which decreased only within the first 2 weeks of treatment. The above trends in changes of gluco- and mineralocorticoid activity should be taken into consideration in long-term treatment of EH with inhibitors of angiotensin-converting enzyme.

Topics: Adrenal Cortex; Adrenal Cortex Hormones; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Chronic Disease; Delayed-Action Preparations; Female; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Statistics, Nonparametric; Time Factors

Whole-day ambulatory blood pressure monitoring is used to confirm the diagnosis of hypertension and assess the response to antihypertensive therapy. Neither of these has been applied to patients with type II diabetes mellitus, in whom it has been proposed that the desirable blood pressure should be lower than in nondiabetics. This multicenter study was designed to examine whether there are differences in the efficacy of a first-line antihypertensive drug when assessed by casual and ambulatory blood pressure determinations in patients with type II diabetes mellitus in whom 24-hour ambulatory monitoring confirms or fails to confirm the diagnosis of hypertension. Forty-three patients (mean age, 57.7 years) with stable type II diabetes mellitus and mild hypertension (casual diastolic pressure, 90 to 104 mm Hg on at least two visits) were treated with an angiotensin-converting enzyme inhibitor (benazepril, 10 to 20 mg, once a day) for 8 weeks. Antihypertensive drug efficacy was assessed by casual (trough) and 24-hour ambulatory blood pressure monitoring. Diabetic patients were classified as nonconfirmed hypertensive if the mean 24-hour ambulatory diastolic pressure was below 85 mm Hg. Antihypertensive treatment significantly decreased both systolic and diastolic pressures when determined by either casual measurement (from a mean of 162.7/98.0 to 153.9/89.2 mm Hg; P < .001) or ambulatory monitoring (from a mean of 143.1/84.4 to 137.0/81.5 mm Hg; P < .05). Twenty-one patients (49%) were classified as confirmed hypertensive and 22 as nonconfirmed hypertensive. In confirmed hypertensive patients benazepril significantly reduced systolic and diastolic pressures when assessed by either casual or 24-hour ambulatory monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Confidence Intervals; Diabetes Mellitus, Type 2; Diastole; Humans; Hypertension; Middle Aged; Prospective Studies; Systole; Time Factors

Benazepril hydrochloride is a non-sulfhydryl-containing, angiotensin-converting enzyme (ACE) inhibitor. The short-term and long-term antihypertensive effects of benazepril remain to be established in Chinese.. Hypertensive subjects with diastolic blood pressure 95-110 mmHg, after two week placebo run-in first, entered a four-week double-blind phase with treatment of benazepril 10 mg once daily or captopril 25 mg three times daily, then received one-year open treatment of benazepril 10 mg daily with or without diuretics. Ambulatory blood pressure monitoring was performed at the end of placebo run-in, after four-week double-blind phase, and after one-year open treatment.. Of the 75 subjects (41 male, 34 female, mean age 57 +/- 12 years, range 34-88 years) who completed the double-blind phase, 42 subjects finished the one-year extension phase. Reasons for withdrawal from the study included irritable cough (16, 21%), hypotension (1, 1%), and poor compliance (16, 21%). During the short-term double-blind phase, benazepril reduced clinic and mean 24-h ambulatory blood pressure by -21/-10 mmHg and by -17/-10 mmHg respectively, and captopril by -21/-13 mmHg and by -17/-10 mmHg respectively. After one-year open treatment by benazepril for the 42 subjects, the one-year average clinic blood pressure was 134/88 mmHg (155/104 mmHg at entry and 135/93 mmHg at the end of the double-blind phase), and the mean 24-h ambulatory blood pressure was 137/87 mmHg (149/95 mmHg at entry and 132/84 mmHg at the end of the double-blind phase).. The antihypertensive effect of benazepril 10 mg daily with or without diuretics is not significantly different from that of captopril 75 mg daily in the short-term and can reasonably be maintained for one year.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Captopril; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Time Factors

A single-blind, run-in, randomized, double-blind, parallel-group, placebo-controlled comparison trial was conducted to assess the safety and efficacy of low-dose amlodipine 2.5 mg daily, low-dose benazepril 10 mg daily, and the combination of the two drugs at the same doses used once daily in patients (n = 401) with mild to moderate (stages I and II) systemic hypertension. Both monotherapy regimens were shown to significantly reduce both systolic and diastolic blood pressure compared with baseline placebo values, and the combination regimen was shown to be superior in lowering systolic and diastolic blood pressure when compared with either of the monotherapy regimens. The combination therapy also resulted in a greater percentage of patients having successful clinical response in mean sitting diastolic blood pressure. The amlodipine and benazepril regimen was also shown to be associated with a similar incidence of adverse experiences as the active monotherapy or placebo regimens, although the group given combination therapy appeared to have a lower incidence of edema than the group given amlodipine alone. Low-dose amlodipine (2.5 mg) plus benazepril (10 mg) provides greater blood-pressure-lowering efficacy than either monotherapy, and has an excellent safety profile.

Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Calcium Channel Blockers; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged

A double blind placebo-controlled trial was performed to evaluate antihypertension efficacy and tolerance of a new inhibitor of angiotensin-converting enzyme benazepril (a single daily dose 10-20 mg) versus captopril (50 mg 1-2 times daily) in 30 patients with mild and moderate hypertension. Monotherapy with benazepril continued 8 weeks. Antihypertension efficacy of benazepril made up 71%, of captopril 64%. Side effects occurred in 2 patients on benazepril and 1 on captopril. These two drugs produced no negative effects on renal function, electrolyte and lipid metabolism, but induced glucose lowering. Thus, benazepril single daily administration in patients with mild and moderate hypertension is effective and is tolerated well.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Captopril; Data Interpretation, Statistical; Double-Blind Method; Drug Tolerance; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Models, Theoretical; Time Factors

In a double-blind, placebo-controlled, three-period cross-over, randomized study we evaluated the efficacy and tolerability of a fixed combination of benazepril 20 mg and hydrochlorothiazide 25 mg (BN + HCT) as compared with the fixed combination of captopril 50 mg and hydrochlorothiazide 25 mg (CP + HCT) by ambulatory blood pressure monitoring (ABPM) in patients with mild to moderate hypertension. Eighteen outpatients, 16 men and 2 women aged 41-58 years, were randomized to receive BN + HCT, CP + HCT, or placebo, all administered once daily for 4 weeks according to a three-period cross-over arranged in a 3 x 3 latin square design. Patients were checked after an initial 3-week washout period and every 4 weeks thereafter. At each visit, 24-h ABPM was performed by a noninvasive device (Spacelabs 5300); causal BP and heart rate (HR) were also measured. Both fixed combinations had a clear-cut antihypertensive effect in comparison with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Analysis of Variance; Antihypertensive Agents; Benzazepines; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Captopril; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Heart Rate; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Outpatients

A double-blind, crossover, placebo-controlled study was undertaken in order to assess the antihypertensive efficacy of a fixed combination of benazepril and hydrochlorothiazide in two different dosages by ambulatory blood pressure monitoring (ABPM). After a three-week placebo wash-out period, 18 patients with mild to moderate essential hypertension, all males, aged 41-60 years, were randomized to receive benazepril 5 mg + hydrochlorothiazide 6.25 mg, benazepril 10 mg + hydrochlorothiazide 12.5 mg or placebo, all given once daily for 4 weeks, according to a 3 crossover period, arranged in a 3 x 3 latin square design. Patients were checked after the wash-out period and every 4 weeks thereafter. At each visit, 24-hour ABPM was performed by a non-invasive device (Spacelabs 90202); causal BP (by mercury sphygmomanometer) and HR were also measured. Both dosages of the fixed combination were equally effective in reducing systolic and diastolic BP values throughout the 24-hour period as compared to the placebo. The antihypertensive effect of the drug could be observed to a similar extent both during the day and night and was still significant 24-hour post-dosing. In addition, the fixed combination did not affect the normal BP circadian variability.

Topics: Adult; Aged; Antihypertensive Agents; Benzazepines; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Heart Rate; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged

The effects of different doses of the angiotensin-converting enzyme inhibitor benazepril on cardiovascular response to a set of standardized laboratory tasks were analyzed. Eighteen patients (15 men and 3 women) with mild-to-moderate essential hypertension were randomly allocated to receive 10 or 20 mg of benazepril, or placebo, each administered once daily for 2 weeks, according to a double-blind, 3-period design. At the end of each treatment period, patients were examined at resting baseline and while performing mental arithmetic, handgrip and cycle ergometry tests. In comparison with placebo, the average reductions in resting systolic blood pressure (BP) were 8.7 mm Hg (95% confidence intervals [CI] -15.2 to -2.1) with 10 mg of benazepril, and 7.8 mm Hg (95% CI -14.4 to -1.3) with 20 mg; the corresponding reductions in resting diastolic BP were 5.1 mm Hg (95% CI -8.7 to -1.4) and 6.8 mm Hg (95% CI -10.4 to -3.1) (all p < 0.05). During mental arithmetic, the reductions in systolic BP were 10.4 mm Hg (95% CI -17.4 to -3.4) with 10 mg of benazepril, and 13.8 mm Hg (95% CI -20.8 to -6.8) with 20 mg; diastolic BP was reduced by 4.5 mm Hg (95% CI -8.5 to -0.5) and 8.3 mm Hg (95% CI -13.2 to -4.3), respectively (all p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Double-Blind Method; Exercise Test; Female; Hand; Heart Rate; Humans; Hypertension; Male; Middle Aged; Muscle Contraction; Physical Exertion; Placebos; Stress, Physiological; Thinking

The antihypertensive activity and the influence of adrenal cortex hormones of benazepril versus captopril were studied in 30 essential hypertensives in a double-blind, randomised, placebo-controlled trial during eight weeks of treatment. Patients started with 50 mg of captopril or 10 mg of benazepril once daily; if normotension had not been obtained after four weeks of treatment the doses were increased to 50 mg twice daily or 20 mg once daily, respectively. 11-Oxycorticosteroids and progesterone in males were measured in blood and daily urine at baseline and at the 4th and the 15th days of drug administration, as well as aldosterone in daily urine by radioimmunoassay, and compared with these data in 15 healthy subjects. Following eight weeks of treatment in 64% and 56% of patients treated with benazepril and captopril respectively, blood pressure was normalised. In the corresponding remaining 14% and 13%, diastolic blood pressure decreased by 10 mmHg and more but not below 90 mmHg. Before treatment excretion of 11-oxycorticosteroids, progesterone and aldosterone was significantly increased without changes in blood levels. After two weeks of treatment 11-oxycorticosteroids and aldosterone excretion decreased (P < 0.05) without progesterone changes, benazepril treatment being more effective in decreasing 11-oxycorticosteroids levels in blood (P < 0.05). In patients with high pretreatment levels of 11-oxycorticosteroids in urine we have noticed the highest antihypertensive effect of both drugs. The main conclusions are that both the ACE inhibitors are effective in mild to moderate essential hypertensives and might decrease glucocorticoids in urine and blood.

Topics: Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Captopril; Female; Glucocorticoids; Humans; Hypertension; Male; Middle Aged; Progesterone

To evaluate the efficacy and safety of benazepril versus captopril in patients with mild or moderate systemic arterial hypertension (SAH).. A multicenter, double-blind, randomized trial analyzed 174 patients, mean age of 52 +/- 9 years, 68 (39%) men. After 2 weeks under placebo, 90 patients were treated, during 6 weeks, with 10 mg, once a day, of benazepril (BZ) and 50 mg, twice a day, of captopril (CPT). At week 3, 25 mg of hydrochlorothiazide (HCT) was added if diastolic blood pressure (DBP) was greater than 90 mmHg. Side effects were analyzed as a not related, unlikely, possible, probable and definitive regard to treatment.. Systolic (p < 0.001) and DBP (p < 0.0001) reductions were observed in both groups. Additional reduction was observed in both groups when 25 mg of HCT was added in patients with DBP > 90 mmHg at week 3. Heart rate was unchanged. The response to treatment was better at BZ group (74% versus 59% of good and excellent response; p = 0.037). Side effects classified as probable or definitive in relation to the treatment occur in 3 (3%) and 10 (11%), respectively at BZ an CPT groups. Laboratorial changes were not observed during treatment.. BZ (10 mg) was superior to CPT (50 mg) in patients with discrete and moderate SAH.

Topics: Adult; Aged; Benzazepines; Captopril; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged

The hemodynamic and cardiac effects of the new angiotensin-converting enzyme inhibitor, benazepril, were studied in 28 hypertensives in a double blind, placebo-controlled, between-patient study. Hemodynamic studies were performed noninvasively by means of M-mode echo (central hemodynamics and left ventricular systolic function), 2-D echo-Doppler (left ventricular diastolic function), and pulsed Doppler flowmetry (forearm circulation). Examinations were done at the end of a placebo run-in period and 3 hours after benazepril administration, both on the first day and after 6 weeks of treatment (10 or 20 mg once daily, according to patient response). In comparison with placebo, benazepril reduced systolic (p = 0.04) and diastolic (p = 0.003) blood pressure, because of a significant reduction in systemic vascular resistance (p = 0.03), while cardiac output was unchanged. Forearm vascular resistance was reduced and brachial artery compliance increased, although not to a statistically significant level (both p = 0.07). Both systolic and diastolic left ventricular function were positively influenced by the afterload reduction: End-systolic stress was reduced by 12% (p = 0.07), as was the late diastolic peak flow velocity (p = 0.02). All hemodynamic changes were evident after acute benazepril administration, and no differences was observed between acute and repeated treatment. We conclude that, similar to other ACE-inhibitors, benazepril reduces blood pressure through a reduction in vascular resistance, while cardiac output and heart rate are unaffected. These hemodynamic effects occur as early as after the first administration and exert a favorable influence on left ventricular dynamics.

Topics: Adult; Antihypertensive Agents; Benzazepines; Blood Circulation; Double-Blind Method; Drug Tolerance; Female; Forearm; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Placebos

In essential hypertension, captopril attenuates forearm vasoconstriction reflexly induced by deactivation of cardiopulmonary and arterial baroreceptors, thus exerting a sympathomoderating effect. We investigated whether this is a common effect of angiotensin converting enzyme (ACE) inhibitors.. Cardiopulmonary and arterial baroreceptors were deactivated by progressively reducing central venous pressure (CVP) through progressively greater lower body negative pressures in eight untreated mild essential hypertensives on a moderately low-sodium diet (50 mmol/l per day). This deactivation was performed after oral administration of the non-sulphidrylic ACE inhibitor benazepril (10 mg) and placebo according to a double-blind randomized crossover experimental design.. After placebo, the reduction in CVP increased forearm vascular resistance (FVR; mean arterial pressure: plethysmographic forearm blood flow ratio). After benazepril, baseline blood pressure (beat-to-beat finger pressure) and FVR were significantly reduced whilst plasma angiotensin II was suppressed and PRA increased (both measured by radioimmunoassay). The FVR increases induced by progressive CVP reduction were less than after placebo administration, and the overall difference was statistically significant. Benazepril did not affect the reflex FVR reduction observed by increasing CVP through leg raising, nor the reflex changes in plasma norepinephrine measured by high-performance liquid chromatography accompanying the changes in FVR.. Benazepril attenuates sympathetic vasoconstriction as does captopril. This effect (which is mainly operative during an increased sympathetic drive and exerted through a reduction of adrenoceptor responsiveness) is thus likely to be a class- rather than a compound-related feature.

Topics: Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Diet, Sodium-Restricted; Double-Blind Method; Female; Humans; Hypertension; Lower Body Negative Pressure; Male; Middle Aged; Norepinephrine; Pressoreceptors; Renin-Angiotensin System; Sympathetic Nervous System; Vascular Resistance; Vasoconstriction

Serum lipids of 80 patients with moderately severe essential hypertension under four different antihypertensive therapies were compared to ten matched hypertensives on a placebo, after eight weeks of therapy. The results in the serum lipid parameters measured after therapy showed with enalapril a significant increase in high-density lipoprotein cholesterol (HDL-C) and a decrease in the total cholesterol/HDL-C ratio. With benazepril a significant decrease in the total cholesterol/HDL-C ratio was obtained. With the diuretic combination Epitens the effect on serum sodium and potassium was minimal. No significant changes were found in the lipoprotein profile following the administration of the placebo. Both angiotensin converting enzyme inhibitors (enalapril and benazapril) induced a significant improvement in the atherogenic ratio; as well as the calcium antagonist (isradipine), though to a less extent. The diuretic Epitens induced an insignificant deterioration of the atherogenic ratio.

Topics: Adult; Antihypertensive Agents; Benzazepines; Blood Pressure; Cholesterol; Cholesterol, HDL; Drug Combinations; Enalapril; Humans; Hypertension; Isradipine; Triamterene; Triglycerides; Xipamide

Benazepril, a newer angiotensin-converting enzyme inhibitor, has been evaluated for the treatment of mild to moderate hypertension in patients 55 years of age and older. The results of the clinical trials conducted to date indicate that benazepril provides effective antihypertensive therapy in this population, with efficacy comparable to that demonstrated in younger patients. Benazepril does not produce precipitous decreases in diastolic blood pressure following the initial dose, and is well tolerated by the elderly. It has a safety profile similar to that of placebo and generally better than that of hydrochlorothiazide.

Topics: Aged; Aged, 80 and over; Aging; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Humans; Hypertension; Middle Aged

Benazepril hydrochloride is a new angiotensin-converting enzyme inhibitor. In a multicenter study, 206 patients with mild to moderate hypertension were randomized to receive benazepril at a dose of 2, 5, 10, or 20 mg, hydrochlorothiazide, 25 mg, or placebo once daily for 4 weeks. The 20 mg dosage of benazepril lowered blood pressure to a degree equal to that of 25 mg hydrochlorothiazide: -12.2/7.7 mm Hg and -13.4/-7.5 mm Hg, respectively. Hydrochlorothiazide proved to be more effective in black subjects. At lower dosage levels of benazepril (2, 5, and 10 mg), blood pressure reduction was not significantly different from that with placebo. In those patients who failed to achieve goal diastolic blood pressure of less than 90 mm Hg with monotherapy after 4 weeks, the addition of open-label hydrochlorothiazide (25 mg/day) to benazepril, hydrochlorothiazide, or placebo produced a substantial additional decrease in blood pressure over a 2-week period. No definite adverse effects on hematologic measurements, serum biochemistry test results, or urinalyses were noted. Subjective adverse experiences were common in all groups but except in three or possibly four instances were not considered causally related to the study drug.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Black People; Blood Pressure; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Renin

This study evaluated the blood pressure effects of administration of once daily oral benazepril hydrochloride, a new angiotensin-converting enzyme (ACE) inhibitor, for mild-to-moderate hypertension. After a 2 to 4 week placebo baseline period, patients with diastolic blood pressure between 95 and 114 mm Hg, were randomized to receive either placebo or benazepril hydrochloride, 5, 10, 20, or 40 mg, once daily in double-blind fashion for 28 days. Blood pressure was measured predose and at 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours after the dose during inpatient observation days at the end of the placebo baseline period, and on the first and last day of the double-blind treatment period; and 24 hours after the dose at weekly outpatient visits. All doses of benazepril hydrochloride resulted in clinically important reductions in diastolic and systolic blood pressures that lasted between 12 and 24 hours after both the first dose, and following the last dose after 4 weeks of treatment. The findings indicate that benazepril hydrochloride may be clinically useful as once-daily monotherapy in many patients with hypertension.

Topics: Administration, Oral; Adolescent; Adult; Antihypertensive Agents; Benzazepines; Blood Pressure; Circadian Rhythm; Diastole; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hypertension; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Systole

The antihypertensive effect of the new non-sulphydryl ACE-inhibitor benzepril was studied in 30 patients (16 men, 14 women; mean age 50 +/- 7 years) with essential hypertension at WHO stage I or II. After a 2-week placebo treatment, patients with lying diastolic blood pressure (DBP) greater than or equal to 95 mmHg were given benzepril 10 mg once daily for 2 weeks. At the end of this period, patients with lying DBP less than 95 mmHg continued with the same dosage, while those with lying DBP greater than or equal to 95 mmHg were blindly up-titrated to benazepril 20 mg once daily. In both cases treatment was continued for further 4 weeks. BP was measured every two weeks 24-26 h after last drug administration. After the run-in period, mean group lying BP was 160/104 +/- 8/5 mmHg. Benazepril significantly reduced systolic blood pressure (SBP) and DBP, both supine and standing (p less than 0.01), while heart rate (HR) did not change. After the first 2 weeks, 13 patients (43%) had lying DBP less than 95 mmHg ("fast responders"), while 17 patients (57%) had DBP greater than or equal to 95 mmHg. By increasing the dosage to 20 mg, a further 5 patients became responder and mean group blood pressure in patients up-titrated with benazepril dropped significantly (-16/-10 mmHg from baseline; p less than 0.01, "slow responders"). Fast responders were younger (47 +/- 5 vs 54 +/- 8 years), had lower baseline BP (160/99 +/- 4/3 vs 173/107 +/- 7/3) and had shorter duration of hypertension (20 +/- 14 vs 61 +/- 27 months) than "slow responders".(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Antihypertensive Agents; Benzazepines; Blood Pressure; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Posture; Randomized Controlled Trials as Topic

To verify the hypothesis that the angiotensin converting enzyme (ACE) level may affect the metabolism of circulating atrial natriuretic factor (ANF), the acute and chronic effects of benazepril on plasma ANF levels were studied in hypertensive patients under basal conditions and in response to acute volume expansion. Ten essential hypertensives entered a double-blind crossover study, and were randomly allocated either to placebo or to 10 mg benazepril orally once a day for 2 days; after a placebo washout period of 2 days the groups were crossed over. On the second day of each crossover period, volume expansion was induced by infusing 1 litre saline in 30 min, and blood samples for ANF measurements were drawn at times -5, 0, 5, 15, 30, 35, 40, 50 and 60 min. Oral benazepril at 10 mg/day was then given to all patients for 4 weeks, and the volume expansion with saline was repeated. After the 2-day acute benazepril treatment, blood pressure fell from 166.1 +/- 3.6/105.1 +/- 0.9 to 140.1 +/- 4.6/85.6 +/- 2.1 mmHg (P less than 0.01 for both systolic and diastolic blood pressure), whereas ANF fell from 29.4 +/- 3.6 to 24.1 +/- 3.7 pg/ml (NS) after the acute benazepril treatment and to 17.7 +/- 3.6 pg/ml (P less than 0.01) after the chronic benazepril treatment. The volume expansion itself did not induce significant changes in mean arterial pressure, either during the placebo treatment or during the acute chronic benazepril treatment. The rise in ANF values in response to saline infusion during placebo was prompt, beginning at min 15 and reaching a maximum at min 40.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atrial Natriuretic Factor; Benzazepines; Blood Pressure; Blood Volume; Double-Blind Method; Humans; Hypertension; Middle Aged; Peptidyl-Dipeptidase A; Randomized Controlled Trials as Topic; Time Factors

Benazepril was shown in preclinical studies to be a potent and specific inhibitor of angiotensin-converting enzyme with a benign toxicologic profile. Its onset and duration of action and the dose-response relationship of its antihypertensive effect have been evaluated. The results of these studies show that 20 mg of benazepril once daily lowers blood pressure by a clinically important amount, which was statistically superior to placebo in three double-blind studies. Doses as low as 10 mg once daily may be effective in individual patients. Doses of 40 and 80 mg once daily have been evaluated and provide small further reductions beyond those seen with the 20 mg dose. Adverse effects are uncommon and generally not dose related. Thiazide diuretics add to the antihypertensive action of benazepril, which has little effect on blood chemistry, apart from a slight rise in serum potassium.

Topics: Benzazepines; Blood Pressure; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Hydrochlorothiazide; Hypertension; Prodrugs; Random Allocation

In order to determine the dose regimen of new antihypertensive compounds, between-patient trials are usually performed. However, the combined use of a crossover design and a precise methodology to measure blood pressure (BP) and biological effects can provide relevant data with a minimal number of patients, if there is no carryover effect which invalidates the experiment. Such goals were successfully achieved with just 25 hypertensive patients who were randomly allocated in double-blind fashion every 2 weeks to a new angiotensin converting enzyme (ACE) inhibitor, benazepril [10 mg once a day (o.d.), 20 mg o.d., 10 mg twice a day (b.i.d.) and 20 mg b.i.d.], or a placebo. The mean BP fall [systolic (SBP)/diastolic (DBP), measured in mmHg] just before drug intake was significantly greater with benazepril: -14/-9 (10 mg o.d.); -15/-8.5 (20 mg o.d.); -22.5/-14 (10 mg b.i.d.), and -21/-13 (20 mg b.i.d.) in comparison with placebo (-3/-3). Mean active plasma renin (measured in pg/ml), assessed by an immunoradiometric assay based on two monoclonal antibodies, increased significantly in a dose-dependent manner, by +0.7 (placebo), +15.0 (10 mg o.d.), +23.4 (20 mg o.d.), +44.4 (10 mg b.i.d.) and +78.8 (20 mg b.i.d.), whereas plasma ACE decreased (by 67 and 78% after 10 and 20 mg o.d., respectively, and by 91-92% after 10 and 20 mg b.i.d.). In the clinical development of an antihypertensive drug, the earlier use of such within-patient studies, with the random insertion of one placebo period between the active periods, should help in the dose-response curve search.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aldosterone; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure Determination; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hypertension; Male; Middle Aged; Patient Compliance; Renin

To compare the potential beneficial effects of the angiotensin converting enzyme inhibitor (ACEI) benazepril and the angiotensin II receptor 1 blocker (ARB) irbesartan on vaginal vascular remodeling and fibrosis in female spontaneously hypertensive rats (SHRs).. Twelve-week-old female SHRs were treated with irbesartan or benazepril for 12 weeks. Vaginal renin angiotensin system (RAS) components were detected by polymerase chain reaction and western blot and vaginal α-smooth muscle actin (α-SMA), endothelial nitric oxide synthase (eNOS), and collagen III (Col III) were analyzed by western blot. Vaginal tissue sections were examined by hematoxylin and eosin staining, Masson trichrome staining, and immunohistochemical analysis of α-SMA and Col III.. Irbesartan and benazepril had different impacts on vaginal RAS components. Both agents decreased vaginal α-SMA and Col III and increased eNOS expression in SHR. The wall/lumen thickness ratio of vaginal arterioles was similarly decreased following irbesartan and benazepril treatment. Both drugs also decreased collagen deposition in SHRs. There was no difference in vaginal vascular remodeling or fibrosis between the two groups.. Irbesartan and benazepril have different effects on vaginal RAS expression but similar positive effects against vaginal vascular remodeling and fibrosis.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Blood Pressure; Female; Fibrosis; Hypertension; Irbesartan; Rats; Rats, Inbred SHR; Tetrazoles; Vascular Remodeling

To investigate factors associated with long-term visual outcome in cats with hypertensive chorioretinopathy.. Eighty-eight client-owned cats diagnosed with hypertensive chorioretinopathy.. Medical records from cats with systemic hypertension and associated retinal lesions were reviewed.. Most cats (61%) were blind in both eyes at presentation. Presence of menace response at last follow-up evaluation was positively correlated with presence of menace response at presentation (P = .0025), time to complete retinal reattachment (P < .0001), and gender (P = .0137). Seventy-six of 132 eyes (57.6%) that were blind at presentation regained some vision following treatment. At the time of last evaluation, 101/176 eyes (60%) had a positive menace response, while 34/46 (74%) eyes with a follow-up of >6 months had a positive menace response. Eyes that had a menace response at presentation were 17 and 37 times more likely to have a menace response at last examination compared to eyes blind for less than 2 weeks and eyes blind greater than 2 weeks, respectively. Female cats were overrepresented (62.5% of cases), and male cats were 4.2 times more likely to be visual at time of last examination compared to female cats.. With treatment, the prognosis for long-term vision in cats with hypertensive chorioretinopathy, even following complete retinal detachment, is good.

Topics: Amlodipine; Animals; Antihypertensive Agents; Benzazepines; Blindness; Cat Diseases; Cats; Choroid Diseases; Female; Hypertension; Hypertensive Retinopathy; Male; Prognosis; Treatment Outcome; Vision, Ocular

Schimke immunoosseous dysplasia (SIOD) is a multisystemic condition characterized by early arteriosclerosis and progressive renal insufficiency, among other features. Many SIOD patients have severe, migraine-like headaches, transient neurologic attacks, or cerebral ischemic events. Cerebral events could be exacerbated or precipitated by hypertension, and it is unclear how these are related to arteriosclerotic changes as dyslipidemia is also a feature of SIOD. The correlation between hypercholesterolemia and cardiovascular risk in SIOD is unclear. Also, the etiology and management of headaches is not well characterized. Here we report our clinical observations in the management of SIOD in a patient who was diagnosed in school age despite early signs and symptoms. We describe biallelic variants, including a previously unreported c.1931G>A (p.Arg644Gln) variant in SMARCAL1. We specifically investigated whether migraine-like headaches and progressive nephropathy may be related to blood pressure dysregulation. We found a correlation between tighter blood pressure regulation using ambulatory blood pressure monitoring and a subjective decrease in headache symptoms. We discuss blood pressure medication management in SIOD. We also characterize dyslipidemia relative to atherosclerosis risks and provide new management strategies to consider for optimizing care.

Topics: Anticholesteremic Agents; Antihypertensive Agents; Arteriosclerosis; Atorvastatin; Benzazepines; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Child; Disease Management; DNA Helicases; Dyslipidemias; Female; Gene Expression; Headache; Humans; Hypertension; Mutation; Nephrotic Syndrome; Osteochondrodysplasias; Primary Immunodeficiency Diseases; Propranolol; Pulmonary Embolism

The ACCOMPLISH (Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension) trial demonstrated that combination therapy using amlodipine, rather than hydrochlorothiazide, in conjunction with benazepril provided greater cardiovascular risk reduction among high-risk hypertensive patients. Few trials have evaluated the effect of prior antihypertensive therapy used among participants on the study outcomes.. In a post hoc observational analysis, we examined the characteristics of the drug regimens taken before trial enrollment in the context of the primary composite outcome (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac death, and coronary revascularization). In the "primary subgroup" (n=4475), patients previously taking any renin-angiotensin system blockade plus either a diuretic or a calcium channel blocker alone or as part of their antihypertensive regimen, there were 206 of 2193 (9.4%) versus 281 of 2282 (12.3%) primary composite events among those randomized to combination therapy involving amlodipine versus hydrochlorothiazide, respectively (adjusted Cox proportional hazard ratio, 0.74; 95% confidence interval, 0.62-0.89;. When combined with an angiotensin-converting enzyme inhibitor, amlodipine provides cardiovascular risk reduction superior to hydrochlorothiazide, largely regardless of prior medication use. These findings add further support for the initial use of this combination regimen among high-risk hypertensive patients.

Topics: Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Calcium Channel Blockers; Cause of Death; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Sodium Chloride Symporter Inhibitors; Time Factors; Treatment Outcome

Investigate the influence of benazepril and amlodipine on the expression of secretin (PZ) and somatostatin (SS) in spontaneously hypertensive rats (SHR).. Forty-five SHRs (14 weeks old, male) were randomly assigned into 3 groups (. After 8 weeks of intervention, compared with the WKY group, the expression of protein and mRNA of PZ in duodenum and SS in sinuses ventriculi was increased significantly in SHR group (. The regulation disorder of PZ in duodenum and SS in sinuses ventriculi exists in SHR. The antihypertensive effect of benazepril and amlodipine may be realized by regulating the expression of PZ and SS, while the regulation of amlodipine is more obvious than benazepril.

Topics: Amlodipine; Animals; Antihypertensive Agents; Benzazepines; Blood Pressure; Hypertension; Male; Random Allocation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Secretin; Somatostatin

To investigate the effects of different drugs on systolic blood pressure (SBP) and left ventricular hypertrophy (LVH) in spontaneously hypertensive rats under cold stress.. A total of 40 male spontaneously hypertensive rats aged 10 weeks (160~200 g) were given adaptive feeding for 7 days at a temperature of 20±1°C and then randomly divided into control group, cold stress group, metoprolol group, amlodipine group, and benazepril group, with 8 rats in each group. SBP, body weight, and heart rate were measured once a week. After the rats were sacrificed by exsanguination, left ventricular weight (LVW) was measured, and left ventricular weight index (LVWI; mg/g) was calculated. Radioimmunoassay was used to measure the concentrations of endothelin-1 (ET-1) and angiotensin-II (Ang-II) in plasma and myocardium, and the chemical method was used to measure the concentrations of nitric oxide (NO) in plasma and myocardium. RT-PCR was used to measure the mRNA expression of endothelin-A receptor.. Compared with the cold stress group, all medication groups showed significant reductions in SBP since week 5 (P<0.05). The cold stress group showed a significant increase in LVWI compared with the control group (3.38±0.27 mg/g vs 2.89±0.19 mg/g, P<0.05). The amlodipine group showed a significant reduction in LVWI compared with the cold stress group (2.98±0.28 mg/g vs 3.38±0.27 mg/g, P<0.05). The cold stress group showed a significant reduction in plasma NO concentration compared with the control group (104.9±19.5 μmol/L vs 129.3±17.8 μmol/L, P<0.05) ; compared with the cold stress group, all the medication groups showed significant increases in blood NO concentration (P<0.05). The cold stress group showed a significant increase in myocardial ET-1 concentration compared with the control group (6.3±1.5 pg/100 mg vs 4.5±1.9 pg/100 mg, P<0.05) ; compared with the cold stress group, the amlodipine group showed a significant reduction in myocardial ET-1 concentration (4.4±1.0 pg/100 mg vs 6.3±1.5 pg/100 mg, P<0.05). The cold stress group had significantly higher mRNA expression of endothelin-A receptor than the control group (0.86±0.23 vs 0.45±0.16, P<0.01) ; compared with the cold stress group, the amlodipine group showed a significant reduction in the mRNA expression of endothelin-A receptor (0.41±0.14 vs 0.86±0.23, P<0.01).. Amlodipine can reduce the increase in SBP and inhibit LVH in spontaneously hypertensive rats under cold stress.

Topics: Angiotensin II; Animals; Benzazepines; Blood Pressure; Cold Temperature; Endothelin-1; Hypertension; Hypertrophy, Left Ventricular; Male; Myocardium; Rats; Rats, Inbred SHR; Stress, Physiological

The effect of angiotensin-converting enzyme inhibitors on hypertension patients regarding endothelial progenitor cell (EPC) functions is poorly understood. The aim of this study was to investigate the effects of benazepril on the proliferation, adhesion and migration capacity of EPCs and its possible mechanism. The functions of EPCs from hypertension patients were obviously reduced compared with control group, and this could be improved by benazepril in a dose-dependent manner, whereas this improvement were obviously blocked when AMD3100 were used together. Therefore, benazepril could obviously improve functions of EPCs from hypertension patients, and the potential mechanism may be related to SDF-1/CXCR4 axis.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Benzylamines; Case-Control Studies; Cell Adhesion; Cell Movement; Cell Proliferation; Cells, Cultured; Chemokine CXCL12; Cyclams; Endothelial Progenitor Cells; Gene Expression; Heterocyclic Compounds; Humans; Hypertension; Receptors, CXCR4; RNA, Messenger

To observe the effect of Shenkang Injection on the blood pressure, metabolism, blood biochemistry and renal pathology in hypertension renal damge rats, then to provide theoretical basis for clinical trials.. 75 spontaneously hypertensive nephropathy rats were randomly divided into five groups with 15 rats in each group: model group (SHR group) rats were intragastrically treated with the vehicle (4 mL/kg normal saline per day) of Shenkang Injection per day; Benazepril group( positive control group, 8 mg/ kg Benazepril per day) ;Shenkang Injection low-dose group (6.7 mL/kg Shenkang Injection per day); middle-dose group (13.3 mL/kg Shenkang Injection per day); high-dose group (26.6 mL/kg Shenkang Injection per day); and WKY rats were normal control group (n = 15) (4 mL/kg normal saline per day).. After 3 months intraperitoneal injection treatment, SHR rats blood pressure were in- hibited; the levels of microalbumin (m-ALB), total protein (U-TP), serum creatinine (Ser) and urea nitrogen (BUN) were decreased significantly in Shenkang Injection treated groups rats. Shenkang Injection significantly improved the levels of creatinine clearance rate (Ccr), serum albumin (ALB) and superoxide dismutase (SOD), decreased the content of methane dicarboxylic aldehyde (MDA), aldosterone (Ald), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1) and C-reactive protein (CRP), and had histologic improvement compared with model group.. Shenkang Injection can improve the kidney function, decrease the levels of serum inflammatory factors,improve the oxidative status and reduce the degree of hypertensive renal damage.

Topics: Animals; Benzazepines; Blood Pressure; C-Reactive Protein; Disease Models, Animal; Drugs, Chinese Herbal; Hypertension; Interleukin-6; Kidney; Kidney Diseases; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

Benazepril, an angiotensin-converting enzyme (ACE) inhibitor, has been used to treat hypertension, congestive heart failure, and chronic renal failure. However, its biological activity and mechanism of action in inflammation are not fully identified. The present study was designed to determine the in vivo anti-inflammatory effects of benazepril on LV hypertrophy in rats.. LV hypertrophy was produced in rats by abdominal aortic coarctation. They were then divided into the following groups: sham operation; LV hypertrophy; LV hypertrophy+benazepril (1mg/kg in a gavage, once a day for 4 weeks). Both morphological assays (hemodynamic and hemorheological measurement; LV hypertrophy assessment), and molecular assays (protein levels of Collagen type I/III, TNF-α and VCAM-1; TGF-β gene expression; NF-κB or Smad activation; intracellular ROS production) were performed.. The following effects were observed in rats treated with benazepril: (1) marked improvements in hemodynamic and hemorheological parameters; (2) significant reductions in LV hypertrophy, dilatation and fibrosis; (3) significantly attenuated protein levels of Collagen type I/III, TGF-β, TNF-α and VCAM-1, NF-κB or Smad activation, as well as intracellular ROS production.. These results suggest that the anti-inflammatory properties of benazepril may be ascribed to their down-regulation of both NF-κB and TGF-β signaling pathways by acting on the intracellular ROS production in rats with LV hypertrophy, thus supporting the use of benazepril as an anti-inflammatory agent.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Inflammatory Agents; Aorta; Aortic Coarctation; Benzazepines; Blood Pressure; Collagen Type I; Collagen Type III; Enzyme Activation; Hemodynamics; Hypertension; Hypertrophy, Left Ventricular; Inflammation; Male; NF-kappa B; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Signal Transduction; Smad Proteins; Transforming Growth Factor beta; Vascular Cell Adhesion Molecule-1

Several studies have suggested an association between ambient air temperature and blood pressure. However, this has not been reliably confirmed by longitudinal studies. Also, whether the reaction to temperature stimulation is modified by other factors such as antihypertensive medication is rarely investigated. The present study explores the relationship between ambient temperature and blood pressure, without and with antihypertensive medication, in a study of 1,831 hypertensive patients followed up for three years, in two or four weekly check ups, accumulating 62,452 follow-up records. Both baseline and follow-up blood pressure showed an inverse association with ambient temperature, which explained 32.4% and 65.6% of variation of systolic blood pressure and diastolic blood pressure (P<0.05) respectively. The amplitude of individual blood pressure fluctuation with temperature throughout a year (a 29 degrees centigrade range) was 9.4/7.3 mmHg. Medication with angiotensin converting enzyme inhibitor benazepril attenuated the blood pressure fluctuation by 2.4/1.3 mmHg each year, though the inverse association of temperature and blood pressure remained. Gender, drinking behavior and body mass index were also found to modify the association between temperature and diastolic blood pressure. The results indicate that ambient temperature may negatively regulate blood pressure. Hypertensive patients should monitor and treat blood pressure more carefully in cold days, and it could be especially important for the males, thinner people and drinkers.

Topics: Alcohol Drinking; Antihypertensive Agents; Benzazepines; Blood Pressure; Body Mass Index; Female; Humans; Hypertension; Linear Models; Longitudinal Studies; Male; Sex Factors; Temperature; Time Factors

The development of essential hypertension (EH) and inter-individual differences in response to antihypertensive treatment may partly result from genetic heterogeneity. In this study, we conducted an investigation of the combined effects of 5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase (MS) A2756G polymorphisms on baseline blood pressure (BP) and BP response to antihypertensive Benazepril treatment in 823 Chinese hypertensive patients with a fixed daily dosage of 10 mg for 15 consecutive days. When MTHFR C677T and MS A2756G polymorphisms were modelled together with adjustment for important covariates, only MTHFR C677T was associated with baseline systolic BP (SBP) (β (s.e.)=2.84 (1.10), P=0.0096) or baseline diastolic BP (DBP) (β (s.e.)=2.19 (0.65), P=0.0008). Modelled together with adjustment for important covariates, MTHFR C677T and MS A2756G polymorphisms were both independently associated with increased DBP response (baseline minus post-treatment) to Benazepril treatment (C677T: β (s.e.)=1.58 (0.76), P=0.038; A2756G: β (s.e.)=2.14 (0.89), P=0.016). Neither polymorphism was associated with SBP response to Benazepril treatment. There were no significant interactions or effect modification between MTHFR C677T and MS A2756G gene polymorphisms in models of baseline SBP, baseline DBP or DBP response to Benazepril treatment. Our results suggest that the effects of MTHFR C677T and MS A2756G gene polymorphisms may have pivotal roles in the aetiology of EH and BP response to Benazepril treatment.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Antihypertensive Agents; Benzazepines; Blood Pressure; Female; Humans; Hypertension; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic; Treatment Outcome

Angiotensin-converting enzyme inhibitors are widely used antihypertensive drugs with individual response variation. We studied whether interactions of AGT, AGTR1 and ACE2 gene polymorphisms affect this response.. Our study is based on a 3-year field trial with 1831 hypertensive patients prescribed benazepril. Generalized multifactor dimensionality reduction was used to explore interaction models and logistic regressions were used to confirm them.. A two-locus model involving the AGT and ACE2 genes was found in males, the sensitive genotypes showed an odds ratio (OR) of 1.9 (95% CI: 1.3-2.8) when compared with nonsensitive genotypes. Two AGT-AGTR1 models were found in females, with an OR of 3.5 (95% CI: 2.0-5.9) and 3.1 (95% CI: 1.8-5.3).. Gender-specific gene-gene interactions of the AGT, AGTR1 and ACE2 genes were associated with individual variation of response to benazepril. Further studies are needed to confirm this finding.

Topics: Adult; Aged; Angiotensin-Converting Enzyme 2; Angiotensinogen; Antihypertensive Agents; Asian People; Benzazepines; Female; Gene Frequency; Humans; Hypertension; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Single Nucleotide; Receptor, Angiotensin, Type 1; Renin-Angiotensin System

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Calcium Channel Blockers; Creatinine; Disease Progression; Diuretics; Drug Therapy, Combination; Glomerular Filtration Rate; Humans; Hydrochlorothiazide; Hypertension; Kidney Failure, Chronic; Renin-Angiotensin System

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Calcium Channel Blockers; Drug Therapy, Combination; Humans; Hypertension; Renin-Angiotensin System; Vasodilator Agents

To explore the correlation of rs2106809 from angiotensin-converting enzyme 2 gene with antihypertensive effects of benazepril, as well as its interactions with polymorphisms of angiotensinogen(AGT) and angiotensin II type 1 receptor(AGTR1) gene.. Correlation between rs2106809 and blood pressure reduction was estimated based on a field trail with 1 831 hypertensive patients using benazepril for 2 weeks. Generalized multifactor dimensionality reduction (GMDR) was used to explore the interactions of rs2106809 and 8 single nucleotide polymorphisms (SNPs) of AGTR1 gene and 3 SNPs of AGT gene.. rs2106809 was found to be associated with reduction in systolic blood pressure and pulse pressure in women, as well as pulse pressure reduction in men. T allele carriers presented more blood pressure reduction (1.4, 1.3 and 0.9 mmHg/T allele respectively). Gene-gene interactions involving rs2106809 were found in systolic blood pressure reduction of men, and the response to benazepril of non-sensitive genotypes carriers was 8.2 (95% confidence interval: 6.6-9.7) mmHg, lower than that of sensitive genotypes carriers.. rs2106809 might act as an independent influencing factor or component of gene-gene interaction in blood pressure reducing effects of benazepril.

Topics: Adult; Aged; Angiotensin-Converting Enzyme 2; Antihypertensive Agents; Benzazepines; Female; Genotype; Humans; Hypertension; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Single Nucleotide; Receptor, Angiotensin, Type 1

1. Advanced glycation end-products (AGE) and their receptors (RAGE) have been implicated in renal damage in diabetes. The aim of the present study was to investigate the effects of benazepril, an angiotensin-converting enzyme inhibitor (ACEI), on the formation of AGE, the expression RAGE and other associated components in the oxidative stress pathway in spontaneously hypertensive rats (SHR). 2. Groups of SHR were treated with or without 10 mg/kg per day benazepril for 12 weeks. Systolic blood pressure (SBP) and angiotensin (Ang) II levels were evaluated in SHR and control Wistar-Kyoto (WKY) rats. Renal function was investigated by determining levels of proteinuria and glomerulosclerosis. Furthermore, reactive oxygen species (ROS) in the rat renal cortex were analysed using an H(2)O(2)-based hydroxyl radical-detection assay and the renal content of AGE, RAGE, NADPH oxidase p47phox, nuclear factor (NF)-kappaB p65, phosphorylated (p-) NF-kappaB p65, vascular cell adhesion molecule (VCAM)-1 and transforming growth factor (TGF)-beta1 was determined by immunohistochemistry, quantitative real-time polymerase chain reaction and western blot analysis. 3. Treatment with benazepril inhibited the formation of AngII, reduced SBP and alleviated renal lesions in SHR compared with both untreated SHR and control WKY rats. Benazepril treatment significantly suppressed the accumulation of AGE and expression of RAGE in the kidney of SHR. In addition, benazepril treatment reduced the upregulation of NADPH oxidase p47phox, ROS generation and NF-kappaB p65, p-NF-kappaB p65, VCAM-1 and TGF-beta1 expression in the kidney of SHR compared with both untreated SHR and control WKY rats. 4. The results of the present study provide new insights into the regulation by the renin-angiotensin system of AGE-RAGE, oxidative stress and nephropathy, increasing our understanding of the role of the RAS in nephropathy.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Benzazepines; Blood Pressure; Disease Models, Animal; Female; Glycation End Products, Advanced; Hypertension; Kidney Cortex; Kidney Diseases; Male; NADPH Oxidases; Oxidative Stress; Phosphorylation; Platelet-Derived Growth Factor; Proteinuria; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reactive Oxygen Species; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Signal Transduction; Transcription Factor RelA; Transforming Growth Factor beta1; Vascular Cell Adhesion Molecule-1

Topics: Amlodipine; Antihypertensive Agents; Benzazepines; Chlorthalidone; Diuretics; Humans; Hydrochlorothiazide; Hypertension; Multicenter Studies as Topic; Randomized Controlled Trials as Topic

The ACCOMPLISH trial consists of a randomized morbidity-mortality study involving 11506 hypertensive patients at high cardiovascular risk, randomly allocated to a fixed dose combination containing an angiotensin converting enzyme inhibitor (B, benazepril) and either a calcium antagonist (A, amlodipine) or a diuretic (HCTZ, hydrochlorothiazide). The target blood pressure (< 140/90 mmHg) was achieved after a 6 month titration period in 75.4% of patients receiving B+A, versus 72.4% in those on B + HCTZ. Over a mean follow-up of 3 years, the B + A drug regimen was found to reduce significantly more effectively the relative risk cardiovascular mortality (-20%), fatal and non fatal myocardial infarction (-22%) and coronary revascularization (-14%), appearing therefore particularly effective to prevent complications due to myocardial ischemia.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Calcium Channel Blockers; Diuretics; Humans; Hydrochlorothiazide; Hypertension; Randomized Controlled Trials as Topic

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Calcium Channel Blockers; Diuretics; Drug Therapy, Combination; Humans; Hydrochlorothiazide; Hypertension; Practice Guidelines as Topic; Practice Patterns, Physicians'; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Calcium Channel Blockers; Chlorthalidone; Diuretics; Drug Therapy, Combination; Humans; Hydrochlorothiazide; Hypertension; Hypokalemia

Topics: Adrenergic beta-Antagonists; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Calcium Channel Blockers; Diuretics; Drug Therapy, Combination; Humans; Hydrochlorothiazide; Hypertension

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Calcium Channel Blockers; Diuretics; Drug Therapy, Combination; Humans; Hydrochlorothiazide; Hypertension

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Calcium Channel Blockers; Drug Therapy, Combination; Humans; Hydrochlorothiazide; Hypertension

Arterial hypertension is an important cardiovascular risk factor. The benefit drawn from decreasing and normalizing the blood pressure level is indisputable. The ACCOMPLISH study performed in patients older than 65 with systolic hypertension and a high cardiovascular risk pointed out the interest of well choosing the antihypertensive combination to reduce this risk beyond the decrease of blood pressure. The association of benazepril (an angiotensin converting enzyme inhibitor or ACEI) and amlodipine (a calcium antagonist) has shown significant early cardiovascular protection in such patients as compared to the classic association including the same ACEI and hydrochlorothiazide, in spite of the same target blood pressure reached. This important finding does not contest the interest of a well controlled blood pressure in hypertension, but probably will modify our first antihypertensive combination choice in the future in patients with such cardiovascular profile.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Cardiovascular Diseases; Humans; Hypertension; Randomized Controlled Trials as Topic; Systole

Marked interindividual variation exists in blood pressure response to benazepril, which is considered to have genetic basis. Our objectives were to evaluate whether the E112D polymorphism in the prolylcarboxypeptidase (PRCP) gene has impact on blood pressure response to benazepril.. Hypertensive patients from Huoqiu County and Yuexi County of Anhui Province received daily treatment with an oral dosage of 10 mg benazepril for 15 days. Genotypes of the E112D polymorphism in the PRCP gene were determined by TaqMan SNP genotyping assay. Multivariate linear and Logistic regressions using generalized estimating equation model were performed in a total of 1092 patients to evaluate the association of PRCP genotypes and blood pressure response to benazepril.. Patients carrying ED or DD genotype had a less systolic blood pressure reduction (adjusted beta = -3.7 + or - 1.1, P < 0.001), a less diastolic blood pressure reduction (adjusted beta = -3.1 + or - 0.8, P < 0.001) and a lower percentage of reaching target blood pressure defined as SBP lower than 140 mmHg and DBP lower than 90 mmHg (adjusted OR = 0.6, P = 0.005) than those patients carrying EE genotype. In addition, the results from stratified analysis by county (Huoqiu or Yuexi) were similar to those observed in the pooled population.. Our data suggest that the E112D polymorphism in the PRCP gene may be a useful genetic marker to predict the antihypertensive effect of short-term benazepril treatment in hypertensive patients of Anhui Province, China.

Topics: Adult; Aged; Antihypertensive Agents; Benzazepines; Blood Pressure; Carboxypeptidases; Female; Genetic Predisposition to Disease; Genotype; Humans; Hypertension; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Young Adult

To assess compliance with antihypertensive therapy and healthcare utilization among African American and White Medicaid recipients who are receiving fixed-dose combination amlodipine besylate/benazepril HCl or a dihydropyridine calcium channel blocker plus an angiotensin-converting enzyme inhibitor prescribed as separate agents (free-combination).. Longitudinal, retrospective, cohort analysis of South Carolina Medicaid claims for the years 1997 through 2002. Followup was 12 months from the index date, defined as the first prescription dispensing date for a study drug.. South Carolina Medicaid beneficiaries receiving fixed-dose (n=3363) and free-combination (n=713) therapy, including 3016 African Americans and 1060 White patients.. Compliance was defined as the total days' supply of drug (excluding last prescription fill) divided by the length of followup; healthcare utilization included cost and number of claims associated with ambulatory services, hospital care, and prescription drugs.. The cohort (N=4076) was 74.0% African American; mean age was 62.2 years. Compliance was significantly greater in patients who received fixed-dose therapy than in those who received free-combination therapy (58.6% vs 48.1%; P<.05). The average total cost of care was lower for the fixed-dose group ($4605) than for the free-combination group ($8531). African Americans and Whites were equally likely to receive the fixed-dose combination. However, compliance was lower among African American patients than among White patients (55% vs 61% respectively; P<.05). Costs and claims for ambulatory and hospital services were higher for African American patients, whereas drug costs and claims were higher for White patients.. Fixed-dose amlodipine besylate/benazepril HCl was associated with higher compliance rates than was free-combination therapy, independent of race. Lower compliance rates among African American patients may have contributed to the higher healthcare resource use and costs observed. Efforts to enhance medication compliance tailored to African Americans may improve outcomes and reduce costs in this high-risk population.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ambulatory Care Facilities; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Black or African American; Calcium Channel Blockers; Cohort Studies; Drug Therapy, Combination; Female; Health Care Costs; Humans; Hypertension; Logistic Models; Male; Medicaid; Middle Aged; Patient Compliance; Retrospective Studies; South Carolina; United States; White People

Topics: Aged; Amlodipine; Antihypertensive Agents; Benzazepines; Blood Pressure; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Amlodipine; Antihypertensive Agents; Benzazepines; Benzimidazoles; Benzoates; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Hypertension; Indapamide; Perindopril; Ramipril; Telmisartan

Topics: Amlodipine; Antihypertensive Agents; Benzazepines; Cardiovascular Diseases; Cause of Death; Drug Combinations; Humans; Hydrochlorothiazide; Hypertension; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Sodium Chloride Symporter Inhibitors; Survival Analysis

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Calcium Channel Blockers; Cardiovascular Diseases; Diuretics; Drug Therapy, Combination; Humans; Hydrochlorothiazide; Hypertension; Risk

Treatment regimens that require fewer dosage units and less frequent dosing to decrease the complexity and cost of care are among the strategies recommended to improve compliance with antihypertensive therapy. Simplifying therapy may be particularly important for elderly patients, who are more likely to have co-morbid conditions and to be taking multiple medications.. To determine rates of compliance with antihypertensive therapy and total costs of care among elderly Medicaid recipients treated with fixed-dose combination amlodipine besylate/benazepril versus a dihydropyridine calcium channel antagonist and ACE inhibitor prescribed as separate agents (free combination).. A longitudinal, retrospective, cohort analysis of South Carolina Medicaid claims for ambulatory services, hospital services, Medicare crossover, and prescription drug for the years 1997-2002. Follow-up was 12 months from the index date, defined as the first prescription dispensing date for a study drug.. South Carolina Medicaid beneficiaries aged >or=65 years.. Outcomes variables included compliance defined as the medication possession ratio (MPR), which was the total days' supply of drug (excluding last prescription fill) divided by the length of follow-up (with number of hospital days subtracted from the numerator and denominator). We hypothesized that elderly individuals receiving fixed-dose combination amlodipine besylate/benazepril HCl would be more compliant with therapy than those receiving a dihydropyridine calcium channel antagonist and ACE inhibitor as free combination.. There were 2336 individuals in the fixed-combination group and 3368 in the free-combination group. The mean age was 76.0 +/- 7.2 years, and 82.6% were female. Compliance rates were significantly higher with fixed-dose versus free-combination therapy (63.4% vs 49.0%; p < 0.0001). The average total cost of care for patients receiving the fixed-dose combination was $US3179 compared with $US5236 (2002 values) for the free-combination regimen. In multivariate regression analyses on the log of total cost of care, average total costs increased by 0.5% for each 1-unit increase in MPR, and for each additional co-morbidity (measured by the chronic disease score) there was an increase of 10.4%. However, average total costs were reduced by 12.5% for patients using fixed-dose versus free-combination therapy (p < 0.003).. Use of fixed-dose amlodipine besylate/benazepril HCl by elderly Medicaid recipients was associated with improved compliance and lower healthcare costs compared with a dihydropyridine calcium channel antagonist and ACE inhibitor prescribed as separate agents.

Topics: Age Factors; Aged; Aged, 80 and over; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Calcium Channel Blockers; Cohort Studies; Dihydropyridines; Drug Combinations; Drug Therapy, Combination; Female; Health Care Costs; Humans; Hypertension; Longitudinal Studies; Male; Medicaid; Patient Compliance; Retrospective Studies; South Carolina; United States

Topics: Adrenal Cortex Hormones; Aged, 80 and over; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Female; Histamine H1 Antagonists; Humans; Hypertension; Tongue Diseases

To identify the genetic contribution to the variation in blood pressure (BP) response to angiotensin-converting enzyme inhibitors (ACEIs), single-nucleotide polymorphisms (SNPs) in the angiotensinogen (AGT), angiotensin receptor 1 (AGTR1), and angiotensin receptor 2 (AGTR2) genes were evaluated for their association with BP response to ACEI in Chinese patients with hypertension in a 2-stage design.. We selected 1447 hypertensive patients from a 3-year benazepril postmarket surveillance trial and genotyped them for 14 SNPs in the AGT, AGTR1, and AGTR2 genes. The AGT rs7079 (C/T) SNP (3'-untranslated region) was significantly associated with the response of diastolic BP to benazepril (diastolic BP response: -7.4 mm Hg for subjects with the CC genotype, -8.9 mm Hg for CA, and -10.1 mm Hg for AA; P=0.001). Although there was no association of individual SNPs in the AGTR1 gene, there was a graded response between common haplotypes and systolic BP reduction in the order of haplotype 2 (H2)/lack of haplotype 3 (non-H3) (-13.6 mm Hg) > non-H2/non-H3 (-10.9 mm Hg) > H3/non-H2 (-6.6 mm Hg) (P=0.004). The total variations in response to ACEI therapy that were explained by the AGT SNP and AGTR1 haplotype groups were 13% for systolic and 9% to 9.6% for diastolic BP, respectively.. AGT SNP rs7079 and AGTR1 haplotypes were associated with BP reduction in response to ACEI therapy in hypertensive Chinese patients. This will be useful in future studies, providing genetic markers to predict the hypertensive response to ACEI therapy.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Benzazepines; Blood Pressure; Female; Haplotypes; Humans; Hypertension; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2

Angiotensin converting enzyme inhibitors are one of the most commonly prescribed medications and angioedema of upper aerogastric tracts is a well recognized complication. Isolated visceral angioedema with the use of angiotensin converting enzyme inhibitors is rare and is relatively under diagnosed. The visceral angioedema should be considered in patients taking angiotensin converting enzyme inhibitors who develop gastrointestinal complaints. We report a case of subacute intestinal obstruction from the use of benazepril, which was promptly resolved after withdrawing benazepril.

Topics: Adult; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Diagnosis, Differential; Female; Humans; Hypertension; Intestinal Diseases; Viscera

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Fosinopril; Glomerular Filtration Rate; Hospitals, Veterans; Humans; Hypertension; Potassium; Retrospective Studies

We studied the effect of hydrochlorothiazide (HCTZ), the angiotensin-converting enzyme inhibitor benazepril, the calcium channel blocker amlodipine, or a combination of benazepril/amlodipine or benazepril/HCTZ on systolic blood pressure (BP) and end-organ injury (left ventricular hypertrophy, proteinuria, and endothelium-dependent relaxation to acetylcholine) in hypertensive Dahl salt-sensitive rats fed either a normal-salt (0.5% NaCl) or high-salt (4% NaCl) diet for 6 weeks. Rats fed a high-salt diet developed hypertension and significant end-organ injury. Monotherapy with HCTZ (75 mg/L in drinking water) or amlodipine (10 mg/kg/day by gavage) reduced systolic BP and proteinuria; benazepril (40 mg/kg/day by gavage) decreased proteinuria without significantly lowering systolic BP. In rats receiving a high-salt diet, only HCTZ reduced left ventricular hypertrophy, whereas endothelium-dependent relaxation was improved by amlodipine and benazepril but not by HCTZ. Combining benazepril with either amlodipine or HCTZ dramatically reduced systolic BP and end-organ injury. These data clearly support clinical studies suggesting that combination therapy is more effective than monotherapy for systolic BP control and prevention of end-organ injury. Complementary mechanisms of action of agents from different antihypertensive classes appear to facilitate the greater benefit on BP and end-organ injury.

Topics: Acetylcholine; Administration, Oral; Amlodipine; Animals; Antihypertensive Agents; Benzazepines; Blood Pressure; Drug Therapy, Combination; Hydrochlorothiazide; Hypertension; Male; Rats; Rats, Inbred Dahl; Sodium Chloride, Dietary; Vasodilation

This is a case report on a 45-year old African-American female with newly diagnosed hypertension, who was started on a combination pill of amlodipine/benazapril 10/5 mg. The very next day, she presented at the emergency room (ER) with abdominal pain, nausea and vomiting. Physical exam, complete metabolic panel, and hemogram were in the normal range. She was discharged from the ER after a few hours of treatment with fluid and analgesics. However, she returned to the ER the next day with the same complaints. This time the physical exam was significant for a distended abdomen with dullness to percussion. CT scan of the abdomen revealed markedly thickened antrum of the stomach, duodenum and jejunum, along with fluid in the abdominal and pelvic cavity. Angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema was suspected, and anti-hypertensive medications were discontinued. Her symptoms improved within the next 24 hours, and repeat CT after 72 hours revealed marked improvement in stomach and small bowel thickening and resolution of ascites. The recognition of angiotensin-converting enzyme (ACE) and angiotensin receptor blocker (ARB) intestinal angioedema constitutes a challenge to primary care physicians, internists, emergency room personal and surgeons.

Topics: Amlodipine; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Calcium Channel Blockers; Female; Humans; Hypertension; Intestine, Small; Middle Aged; Stomach; Tomography, X-Ray Computed

Although multidrug therapy is required in order to achieve good blood pressure control in many hypertensives, there are no studies directly comparing fixed-dose combinations as initial therapy. The Avoiding Cardiovascular events through COMbination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial compares regimens of benazepril plus amlodipine versus benazepril plus hydrochlorothiazide, force-titrated to 40/10 and 40/25mg, respectively. A total of 12,600 high-risk hypertensives have been randomised and will be followed for 3 - 5years, during which cardiovascular events will be monitored. The investigators hypothesise that the benazepril plus amlodipine regimen will decrease cardiovascular events by 15% compared with benazepril plus hydrochlorothiazide. Recruitment began in 2003, and the trial is expected to end in 2008. The ACCOMPLISH trial shares important limitations with many other recent trials that will make it difficult to apply the results in clinical practice. These include the focus on high-risk hypertensive patients, in whom significant reductions in relative risk will translate into meaningful reductions in absolute risk: in lower-risk hypertensives with a low absolute risk, similar relative risk reductions may not be of great impact on the population disease burden. In ACCOMPLISH, as in most industry-sponsored clinical trials, the main goal appears to be market-driven: doses of drugs tested are not those available for clinical practice. The question asked, whether the combination of benazepril with either diuretic or dihydropyridine calcium channel blocker is more efficacious, is not a clinically compelling one. Finally, the univariate subgroup analyses proposed are unlikely to lead to an understanding of whether either combination has specific advantages for patients encountered clinically, most of whom have multiple risk factors. Thus, it appears that ACCOMPLISH, as with many recent pharmacological trials, will not greatly impact the treatment of hypertension.

Topics: Amlodipine; Antihypertensive Agents; Benzazepines; Cardiovascular Diseases; Drug Therapy, Combination; Humans; Hydrochlorothiazide; Hypertension; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Risk Factors

The effects of iptakalim, a new ATP-sensitive potassium channel opener, were studied in spontaneously hypertensive rats (SHR). Treatment of 12-week-old male SHR (six animals in each group) with iptakalim by gastric lavage at doses of 1, 3, or 9 mg/kg/day for 12 weeks resulted in a lowering of blood pressure. Iptakalim provided significant renoprotection to SHR rats as measured by decreased proteinuria and improved renal function. Histological evidence demonstrated that iptakalim could reverse renal vascular remodeling (of afferent arterioles, arcuate arteries, or interlobular arteries), and improve pathological changes of glomerular, renal interstitial, and glomerular filtration membranes. These effects were accompanied by the decreased circulation and intrarenal concentrations of endothelin 1 and transforming growth factor beta1 (TGF-beta1), and down-regulated overexpression of genes for ET-1, endothelin-converting enzyme 1, TGF-beta1, and the subunits of ATP-sensitive potassium channels (K(ATP)), Kir1.1 and Kir6.1, in the kidney during hypertension. Abnormal expression of matrix components [collagen IV, fibronectin, matrix metalloproteinase 9 (MMP-9) and MMP tissue inhibitor 1 (TIMP-1)] was also significantly reversed by iptakalim. Our results demonstrate that chronic treatment with iptakalim not only reduces blood pressure but also preserves renal structure and function in SHR. In addition to reducing blood pressure, the renoprotective of iptakalim may be involved in inhibiting the circulation and intrarenal concentrations of endothelin 1 and TGF-beta1, regulating the expression of K(ATP) genes and correcting MMP-9/TIMP-1 imbalance in renal tissue, which may result in reducing the accumulation of extracellular matrix molecules.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; ATP-Binding Cassette Transporters; Benzazepines; Endothelin-1; Extracellular Matrix; Hemodynamics; Hypertension; Immunohistochemistry; KATP Channels; Kidney; Kidney Diseases; Kidney Function Tests; Potassium Channels, Inwardly Rectifying; Propylamines; Rats; Rats, Inbred SHR; Reverse Transcriptase Polymerase Chain Reaction; Transforming Growth Factor beta; Transforming Growth Factor beta1

Our recent study indicated that MTHFR C677T polymorphism may involve in genetic control of blood pressure response to treatment by benazepril, an ACE inhibitor. Currently, we proposed to further investigate whether short-term blood pressure response to benazepril, was modulated by haplotypes re-constructed from both C677T and A1298C polymorphisms in MTHFR gene. A total of 410 hypertensive patients recruited from 344 nuclear families were treated orally with benazepril at a daily dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. In addition, 689 family members of these patients were also genotyped. Among these patients, the frequency of MTHFR A1298C AA, AC and CC genotypes was 74.4%, 23.9%, and 1.7%, respectively. The frequency of MTHFR C677T CC, CT and TT genotypes was 23.7%, 51.2%, and 25.1%, respectively. Only three haplotypes, 677T-1298A (50.8%), 677C-1298A (35.7%), and 677C-1298C (13.5%) were re-constructed. Multivariate regression models with generalized estimating equation (GEE) correction detected that the individuals carrying one copy of haplotype 677C-1298C had significantly lower diastolic and systolic blood pressure response (DeltaDBP and DeltaSBP) to benazepril treatment (p= 0.003 and p =0.043, respectively), in comparison to those without haplotype 677C-1298C. The results of family-based association test further confirmed that haplotype 677C-1298C was more frequently transmitted in subjects with either lower residual of DeltaDBP or DeltaSBP. For residual of DeltaDBP, the p-values are 0.007 in an additive model and 0.005 in a dominant model. For residual of DeltaSBP, the p-values are 0.009 in an additive model and 0.006 in a dominant model. Our findings suggest that MTHFR 677C-1298C haplotype modulate blood pressure responsiveness to shortterm treatment of ACE inhibitor in Chinese essential hypertensive patients.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Family; Female; Haplotypes; Humans; Hypertension; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic

To investigate the association between M235T variant of angiotensinogen (AGT) gene and the blood pressure response to benazepril in a hypertensive cohort.. Benazepril (10-20 mg/day) was administered for 6 weeks to 251 essential hypertensives. Polymerase chain reaction (PCR) combined with restriction enzyme digestion was used to detect the polymorphism and the patients were classified as MM, MT or TT genotype. The changes in systolic and diastolic blood pressure (SBP and DBP) were analyzed for association with genotypes at the AGT gene locus.. The MM genotype was observed in 23 patients (9.2%), the MT genotype in 104 patients (41.4%) and the TT genotype in 124 patients (49.4%). There was no association between these polymorphisms and the blood pressure responses in the total 251 patients. But based on the analysis stratified by age, the association between these polymorphism and the DBP responses was found in the old patients (> or = 60 years old) subgroup, the reduction in DBP was significantly greater in patients carrying the MM compared to MT or TT genotypes (14.8 +/- 4.8 mm Hg vs. 7.9 +/- 7.7 mm Hg or 9.8 +/- 6.4 mm Hg respectively; ANOVA, P = 0.034).. The M235T polymorphism of the AGT gene was shown to influence the responses to benazepril in old hypertensive patients (> or = 60 years old). Thus, specific genotypes might predict the response to specific antihypertensive treatment.

Topics: Aged; Angiotensinogen; Antihypertensive Agents; Benzazepines; Female; Genotype; Humans; Hypertension; Male; Middle Aged; Polymorphism, Single Nucleotide

CGS 35601 is a potent triple vasopeptidase inhibitor (VPI) of angiotensin-converting enzyme (ACE), neutral endopeptidase (NEP), and endothelin-converting enzyme (ECE). The aim of the study was to determine the effects of this VPI on the hemodynamic profile of conscious, instrumented, unrestrained spontaneously hypertensive rats (SHR), in comparison to selective inhibitors of ACE and ACE + NEP, than +ECE combined. Circulating plasma concentrations of vasoactive mediators and reactive oxygen species were measured.. Old SHR male were instrumented (arterial catheter) and placed in a metabolic cage for daily hemodynamic measurements and blood samplings. Seven days after surgery, SHR received 1) saline vehicle; 2) increasing doses of the triple CGS 35601 (0.01, 0.1, 1, and 5 mg/kg/d, intra-arterially (i.a.) infusion for 5 d/dose) followed by a 5-day washout period; 3) benazepril (ACE inhibitor), ACE inhibitor + CGS 24592 (NEP inhibitor) and ACE inhibitor + NEP inhibitor + CGS 35066 (ECE inhibitor) (1 or 5 mg/kg/d i.a. infusion for 5 d/combination) followed by a 5-day washout period.. The lowest dose of CGS 35601 had no effect. Doses at 0.1, 1, and 5 mg/kg/d reduced mean arterial blood pressure by 10%, 22%, and 40%, respectively. Heart rate was unaffected in all groups. CGS 35601 decreased concentrations of angiotensin II (Ang II), endothelin-1 (ET-1), and pro-atrial natriuretic peptide (proANP), and increased those of big ET-1, atrial natriuretic peptide (ANP), bradykinin (BK), and hydrogen peroxide (H2O2) dose dependently.. The blood pressure-lowering effect of this triple VPI was superior to that of the other VPI in this preclinical rat model of hypertension. Further experiments are needed to assess triple VPI to other combinations in other models with regard to efficacy and angioedema. Only then it may constitute a first-in-class approach for the treatment of hypertension and other cardiovascular disorders.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Aspartic Acid Endopeptidases; Atrial Natriuretic Factor; Benzazepines; Benzofurans; Blood Pressure; Dose-Response Relationship, Drug; Endothelin-1; Endothelin-Converting Enzymes; Hypertension; Indoles; Male; Metalloendopeptidases; Neprilysin; Nitric Oxide; Organophosphonates; Phenylalanine; Protease Inhibitors; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Rats, Wistar; Reactive Oxygen Species

To explore the influence of alcohol consumption during ACEI (Benazepril) therapy on effectiveness of antihypertensive in male patients with essential hypertension.. A prospective cohort study was made and multiple linear regression and multiple logistic regression models were applied to data analysis.. After 15 days ACEI therapy, the decrease in systolic blood pressure (deltaSBP) and diastolic blood pressure (deltaDBP) in alcohol-drinking groups was clearly smaller than that of non-drinking group. An inverse dose-response relation between alcohol drinking and (deltaSBP) as well as (deltaDBP) was observed either. To the non-alcohol-drinking group, subjects with alcohol-drinking more than 50 ml per day showed 5.26 mmHg (0.70 kPa) (P = 0.0116) and 3.32 mmHg (0.44kPa) (P = 0.0349) decreased in NSBP and DDBP, respectively. Logistic regression analysis demonstrated that the alcohol-drinking group's effect rate of antihypertensive were 45% lower (P = 0.0493) in SBP drop and 76% lower (P = 0.4750) in DBP drop respectively compared with non-and alcohol-drinking groups.. Alcohol drinking during ACEI therapy can lower the effectiveness of antihypertensive in male patients with essential hypertension.

Topics: Adult; Alcohol Drinking; Antihypertensive Agents; Benzazepines; China; Humans; Hypertension; Linear Models; Male; Middle Aged; Prospective Studies; Treatment Outcome

Accumulating evidence shows that inhibition of the vascular renin-angiotensin system results in suppression of injury-elicited neointima formation. We attempted to determine whether or not combined treatment with an angiotensin II type 1 receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) has an additive inhibitory effect on balloon-injury-elicited neointima formation in the carotid artery. Male Sprague-Dawley rats were treated with an ARB (valsartan: 3 mg/kg/day) and/or an ACEI (benazepril: 0.3 mg/kg/day) from 1 week before until 2 weeks after balloon injury. Experiments were also conducted with one-third of the dose combination used in the original experiments. Both ARB and ACEI inhibited neointima formation without any blood pressure changes. The full-dose combination lowered blood pressure and suppressed neointima formation significantly compared with the levels in the groups treated with either ACEI or ARB alone. The low-dose combination without blood pressure reduction also inhibited neointima formation to a similar extent as the full-dose combination. We measured 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a marker of oxidative stress, and nitrite and nitrate (NOx), an index of nitric monoxide production, in media conditioned by the injured artery. NOx production was lower and 8-iso-PGF2alpha was higher in the media of the injured artery, compared with those in the normal artery. ACEI restored NOx production more dramatically than ARB, and ARB suppressed 8-iso-PGF2alpha markedly compared with ACEI. These results suggest that the combination of an ARB and an ACEI exerts an additive inhibitory effect, presumably through an increase in production and bioavailability of NO from the endothelium.

Topics: Angioplasty, Balloon; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Benzazepines; Blood Pressure; Carotid Artery Injuries; Disease Models, Animal; Hypertension; Nitric Oxide; Oxidative Stress; Rats; Rats, Sprague-Dawley; Tetrazoles; Tunica Intima; Valine; Valsartan

Essential hypertension, as a complex disorder with unknown etiology cause, is a major public health problem worldwide. Patients need constant drug therapy to maintain their blood pressure in a normal range. However, the current facts suggest that the treatment is not optimized in a large number of patients, and as a result they are at risk for compliance resulting in uncontrolled blood pressure. Genetic and environmental factors associated with individual variation in response to anti-hypertensive drug remain largely unknown.. In order to illustrate the existence and to attempt to identify the factors modifying drug effect, we conducted a large-scale follow-up study in two Chinese rural counties differing in both genetic background and residential environment. Hypertensive patients were treated with benazepril, a commonly used angiotensin converting enzyme inhibitor, for 15 days, and the end-point effect was evaluated.. We found that there were large and significant differences in drug response between subjects from two counties, even after adjustment for known factors. The responses to benazepril, measured in diastolic blood pressure drop, in male patients from Yuexi was twice as effective as their counterparts from Huoqiu.. These results suggest that adjustment of treatment regimen is necessary to improve efficacy, and it could be done at the population level to make it more feasible and affordable.

Topics: Adult; Antihypertensive Agents; Benzazepines; Blood Pressure; Body Composition; China; Female; Follow-Up Studies; Humans; Hypertension; Interviews as Topic; Linear Models; Male; Middle Aged; Pharmacoepidemiology; Rural Health; Treatment Outcome

Topics: Administration, Oral; Aged; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Captopril; Dermatitis, Contact; Female; Fosinopril; Humans; Hypertension; Quinapril; Skin Tests; Tetrahydroisoquinolines

Elevated plasma homocysteine has been implicated as a risk factor for hypertension. C677T polymorphism in methylenetetrahydrofolate reductase gene (MTHFR) is a major determinant of hyperhomocysteinemia, which results in endothelial dysfunction. Angiotensin-converting enzyme (ACE) inhibitors appear to remedy the endothelial dysfunction and restore endothelium-dependent vasodilatation. The co-existence of genetic polymorphisms in drug metabolizing enzymes, targets, receptors, and transporters may influence the drug efficacy. The purpose of this study was to investigate whether short-term blood pressure control by benazepril, an ACE inhibitor, was modulated by C677T MTHFR gene polymorphism.. A total of 444 hypertensive patients, aged 27 to 65 years, without any anti hypertensive therapy within 2 weeks were included. All of them were treated orally with benazepril at a single daily fixed dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. Among them, the frequency of MTHFR C677T genotype CC, CT and TT was 24.3%, 51.8%, and 23.9%, respectively. In a recessive model (CC+CT versus TT genotype), both baseline diastolic blood pressure (DBP) and diastolic blood pressure response (DeltaDBP) were significantly higher in patients with the TT genotype than in those with the CT or CC genotype (P value=0.0076 for DBP, and P value=0.0005 for DeltaDBP). We further divided all patients into three groups based on the tertiles of the DeltaBP distribution. Compared to subjects in the lowest tertile of DeltaDBP, the adjusted relative odds of having the TT genotype among subjects in the highest tertile was 2.6 (95% CI, 1.4 to 4.9). However, baseline systolic blood pressure (SBP) and SBP response did not significantly associate with MTHFR C677T polymorphism.. Our finding suggests that MTHFR C667T polymorphism modulated baseline DBP and DBP responsiveness by short-term treatment of ACE inhibitor in Chinese essential hypertensive patients.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; China; Female; Genetic Predisposition to Disease; Genetic Testing; Genetic Variation; Humans; Hypertension; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic; Prognosis; Risk Assessment; Risk Factors; Statistics as Topic; Treatment Outcome

To introduce the application of mixed linear model in the analysis of secular trend of blood pressure under antihypertensive treatment.. A community-based postmarketing surveillance of benazepril was conducted in 1831 essential hypertensive patients (age range from 35 to 88 years) in Shanghai. Data of blood pressure was analyzed every 3 months with mixed linear model to describe the secular trend of blood pressure and changes of age-specific and gender-specific.. The changing trends of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were found to fit the curvilinear models. A piecewise model was fit for pulse pressure (PP), i.e., curvilinear model in the first 9 months and linear model after 9 months of taking medication. Both blood pressure and its velocity gradually slowed down. There were significant variation for the curve parameters of intercept, slope, and acceleration. Blood pressure in patients with higher initial levels was persistently declining in the 3-year-treatment. However blood pressures of patients with relatively low initial levels remained low when dropped down to some degree. Elderly patients showed high SBP but low DBP, so as with higher PP. The velocity and sizes of blood pressure reductions increased with the initial level of blood pressure.. Mixed linear model is flexible and robust when applied to the analysis of longitudinal data but with missing values and can also make the maximum use of available information.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Female; Humans; Hypertension; Linear Models; Longitudinal Studies; Male; Middle Aged; Product Surveillance, Postmarketing

To investigate the long-term effect, safety and tolerability of benazepril in general hypertensive patients.. We conducted a three-year community-based postmarketing surveillance on benazepril among 1831 essential hypertensive patients (age range from 35 to 88 years) in Shanghai.. 74.3% of patients persisted in medication taking and were with optimal compliance in a 3-year-follow-up program. Among those taking medication as prescribed after 3 years, 75.7% of them attained systolic blood pressure (SBP) target level of 140 mm Hg (1 mm Hg = 0.133 kPa), 87.4% attained diastolic blood pressure (DBP) target level of 90 mm Hg, and 71.5% attained total target level of 140/90 mm Hg. The reductions were approaching 15 mm Hg for SBP, 10 mm Hg for DBP, and 5 mm Hg for pulse pressure (PP) during the 3 year period. No serious adverse drug reactions (ADRs) were detected during the 3 years follow-up. Cough was the most common ADR. The cumulative incidence of benazepril related cough was 23.6% in women, significant higher than in men (18.8%).. Benazepril was safe and tolerable when applied in hypertensive patients.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Benzazepines; China; Cough; Female; Humans; Hypertension; Male; Middle Aged; Product Surveillance, Postmarketing

Angiotensin-converting enzyme (ACE) inhibitors differ in their affinity for tissue-bound ACE. It has been hypothesized that tissue ACE affinity might be responsible for some of the beneficial cardiovascular properties of ACE inhibitors. The present study examined this question and found no correlation between tissue ACE affinity and risk of first nonfatal myocardial infarction in patients who have hypertension.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Calcium Channel Blockers; Case-Control Studies; Drug Therapy, Combination; Female; Humans; Hypertension; Lisinopril; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Quinapril; Tetrahydroisoquinolines; Treatment Outcome; United States

There is considerable variability in individual response to antihypertensive agents. The reason for this is not known, but may be related to individual genetic variability. This study examined whether the therapeutic efficacy of benazepril on essential hypertension is modified by beta2 adrenergic receptor gene (ADRB2) Arg16Gly (R16G) polymorphism.. We conducted a family-based study of 321 and 610 hypertensive subjects from Yuexi and Huoqiu Counties of Anhui, China, respectively. Both systolic and diastolic blood pressures (SBP and DBP) before and after a 15-day benazepril treatment were measured. ADRB2 R16G genotypes were determined for all subjects. ADRB2 G16 allele frequency was found to be 41.0% and. 47.4% in Huoqiu and Yuexi, respectively. In Yuexi family-based association test (FBAT) revealed that the G16 allele was associated with a greater DBP decrease in response to a 15-day benazepril treatment (Z = 2.12, P = 0.03), and the data were consistent with a dominant inheritance model. A similar trend was observed in Huoqiu Chinese, but the magnitudes of effects were smaller and did not reach statistical significance. The FBAT results were further confirmed by using a generalized estimating equation model.. Our family-based study provided the first evidence that ADRB2 R16G polymorphism may play an important role in DBP response to benazepril treatment, although the magnitude of the effect appears to be modified by other risk factors such as plasma lipid and glucose profiles.

Topics: Adult; Antihypertensive Agents; Asian People; Benzazepines; Female; Genotype; Humans; Hypertension; Male; Middle Aged; Polymorphism, Genetic; Receptors, Adrenergic, beta-2

To investigate the association between insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene and the A/B polymorphism of the chymase (CMA) gene with regression of left ventricular hypertrophy (LVH) in patients with essential hypertension and left ventricular hypertrophy. The study subjects had been participants in along-term trial of therapy with an ACE inhibitor.. Follow-up data of 157 patients with essential hypertension and left ventricular hypertrophy were collected. DNA fragments of ACE gene and CMA gene were amplified by PCR and analysed by RFLP. LVDd, IVST and LVPWT were measured by Ultrasonic Cardiogram (UCG).. (1) When long-term treatment with Benazepril was carried out, the blood pressure was markedly decreased and the heart rate was maintained steadily. (2) Regression of left ventricular hypertrophy was improved. (3) The magnitudes of regression of LVM and LVMI during therapy were greater in the DD group than in the II and ID group. No significant differences of other indices were found in the different genotype groups of ACE. (4) No significant differences of all indices were found in the different genotype groups of CMA. (5) No interaction appeared between the genotypes of the ACE and the genotypes of the CMA.. Hypertensive patients with DD genotype were more likely to have regression of left ventricular hypertrophy when treated with ACE inhibitors than patients with other ACE genotypes. No evidence was found to support an association between CMA genotype and regression of LVH in those patients.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Chymases; Female; Follow-Up Studies; Genotype; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Peptidyl-Dipeptidase A; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Serine Endopeptidases

We report the case of a 42 year old patient who developed chronic hyperplastic laryngitis during treatment with the angiotensin converting enzyme-inhibitor Cibacen 10. A severe cough and vocal restrictions with hoarseness were only incompletely cured after changing this anti-hypertensive medication to a adrenergic blocker, combined with a vocal rest and anti-inflammatory inhalation. Therefore we performed a laryngoscopy under general anesthesia and excised the swelling of the vocal cords. Additionally, voice therapy was prescribed and complete restitution achieved. Although hoarseness is documented as a potential side effect of angiotensin converting enzyme-inhibitors, morphological alterations in the vocal cords have not been linked to this type of drug. In our case, prolonged medication with Cibacen 10 led to chronic hyperplastic laryngitis. Initial coughing might have induced the trauma of the epithelium of the vocal cords. Due to the morphological alterations to the vocal cords the patient developed additional functional dysphonia.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Chronic Disease; Humans; Hyperplasia; Hypertension; Laryngitis; Male; Treatment Outcome; Vocal Cords

Inhibition of the renin-angiotensin system with an angiotensin-converting enzyme inhibitor (ACEi) is an effective therapy in hypertension. Vasopeptidase inhibition was initially proposed with compounds inhibiting both angiotensin-converting enzyme and neutral endopeptidase (omapatrilat), but clinical trials revealed that reducing angiotensin II while blocking the degradation of vasodilatory peptides was not without concerns. We have previously investigated the combination of an ACEi with an endothelin-converting enzyme inhibitor (ECEi); now we add a neutral endopeptidase inhibitor (NEPi) toward triple vasopeptidase inhibition. Male spontaneously hypertensive rats were surgically implanted with a vascular catheter and treated with an ACEi (benazepril), a NEPi (CGS 24592) and an ECEi (CGS 35066) (continuous intra-arterial infusion at 1 or 5 mg/kg/day x 5 days each). After 15 days, drugs administration was stopped for 3 days. ACEi (1 mg/kg per day) reduced the mean arterial blood pressure by 8.4%. The addition of a NEPi and an ECEi at the same dose did not shown any added benefit. The mean arterial blood pressure came back to baseline upon cessation of treatment. ACEi (5 mg/kg per day) reduced the mean arterial blood pressure by 28%. The mean arterial blood pressure remained attenuated by 21% and 19% with the addition of the NEPi and the ECEi. Again, the mean arterial blood pressure rose back to 148 +/- 4 mmHg following cessation of treatment. Daily biochemical and hematological analysis of plasma did not reveal any signs of toxicity, except for a rapid elevation in K (40%) after 1 day of ACEi. Thus, angiotensin II inhibition plays a primary role in controlling the blood pressure of spontaneously hypertensive whereas additional NEPi and ECEi did not provide further benefits under the present dose combinations. The normalizing effect of the higher dose of ACEi by itself made it impossible to discriminate the role of neutral endopeptidase and endothelin-converting enzyme-modulated peptides and to further define the paradigm of triple vasopeptidase inhibition toward better control of vascular hemodynamics. Additional studies are underway.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Aspartic Acid Endopeptidases; Benzazepines; Benzofurans; Blood Pressure; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Endothelin-Converting Enzymes; Heart Rate; Hypertension; Infusions, Intra-Arterial; Male; Metalloendopeptidases; Neprilysin; Organophosphonates; Phenylalanine; Rats; Rats, Inbred SHR; Time Factors

To investigate the effect of the insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene on the drug treatment in patients with chronic heart failure.. The genotype was determined by polymerase chain reaction (PCR) in 79 patients with chronic heart failure. Plasma Ang II levels that were assessed by radio-immunity assay (RIA), left ventricular end-diastolic diameters (LVDD) and left ventricular ejection fractions (EF) and that were studied with echocardiography were measured before and after the treatment.. ACE gene DD polymorphism was associated with greater LVDDs [DD vs. ID (P <0.001), DD vs. II (P < 0.001)], higher plasma Ang II levels [DD vs. ID (P < 0.05), DD vs. II (P < 0.001)] and the greatest decreased magnitude of plasma Ang II levels after treatment [DD vs. ID (P < 0.05), DD vs. II (P < 0.001)].. In patients with chronic heart failure, ACE gene DD polymorphism might be a marker of a higher level of activation of the renin-angiotensin system (RAS). Patients with the DD allele would expect a greater beneficial effect on endocrine by the drug treatment including ACE inhibitor and beta-blocker.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Coronary Disease; Female; Gene Frequency; Genotype; Heart Failure; Humans; Hypertension; Male; Metoprolol; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Renin-Angiotensin System; Treatment Outcome

To investigate the risk factors of benazepril related cough.. Case-control study nested in a community-based postmarketing surveillance was carried out. One thousand eight hundred and thirty-one hypertensive patients screened from a Chinese community were recruited to take benazepril for 3 years. Demographic characteristics and behavior risks were investigated and the level of uric acid and creatinine were tested at baseline. Episodes of benazepril related cough during follow period were recorded.. Within half a year of administration, the incidence rates of cough were as high as 18.35% in women and 12.11% in men. Incidence decreased significantly when time went by. Two years later of administration, first occurrences of cough were still seen. Based on logistic regression analysis, women were more likely to develop cough (OR = 2.193, 95% CI: 1.500 - 3.206). The association between decompensated kidney function and cough occurrence was only detected in women (OR = 3.432, 95% CI: 1.954 - 6.028). Women aged 65 or more had 1.672 (95% CI: 1.040 - 2.688) times risk than women aged 35 to 64 years. In men, the OR of developing cough was 1.689 (95% CI: 0.976 - 2.924) for daily drinking alcohol less than 100 g but increased to 2.478 (95% CI: 1.148 - 5.347) when drinking 100 g or more, but not the determinant ones.. Women, older age, drinking alcohol and decompensated kidney function were the possible risk factors for benazepril related cough, but not the determinant ones.

Topics: Adult; Age Factors; Aged; Alcohol Drinking; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Case-Control Studies; China; Cough; Female; Follow-Up Studies; Humans; Hypertension; Incidence; Kidney Function Tests; Logistic Models; Male; Middle Aged; Product Surveillance, Postmarketing; Risk Factors; Sex Factors

To investigate the associations between angiotensin converting enzyme inhibitors (ACEIs) related cough and ACE I/D and bradykinin beta(2) receptor (BDKRB2) C/T polymorphism.. A case-control study, nested in a 3-year community-based postmarketing surveillance of benazepril in 1 831 Chinese hypertensives was carried out. Three hundred and fifty-one cases having suffered benazepril related cough were identified and genotyped. Genotyped controls were selected through a stratified sampling design by age, sex and kidney function status.. The allele frequencies in cases were I 65.4%, D 34.6% and T 53.0%, C 47.0% and the genotype frequencies were II 42.2%, ID 46.4%, DD 11.4% (ACE) and CC 21.6%, CT 50.9%, TT 27.6% (BDKRB2), respectively. Genotype frequencies were both in Hardy-Weinberg equilibrium. According to stratified analyses by sex, kidney function status and age, no association was found between BDKRB2 C/T polymorphism and cough. For ACE I/D polymorphism, in men with decompensated kidney function, patients with ID or DD genotype having 4.805 times the risk of those with II genotype in developing cough. In women aged 35 to 49 years with normal or compensated kidney function, the OR of DD genotype was 5.128. No associations were detected in other subgroups.. It was suggested that kidney function status and some specific characteristics surrogated by age and sex had modified the effect of ACE I/D variant on cough.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Cough; Female; Humans; Hypertension; Male; Middle Aged; Peptidyl-Dipeptidase A

Although recent clinical studies have indicated that angiotensin II receptor blocker is as effective in treating heart failure as an angiotensin-converting enzyme inhibitor, it is unknown whether their effects are different. Dahl salt-sensitive rats were treated with an angiotensin-converting enzyme inhibitor benazepril, and an angiotensin II receptor blocker candesartan from 11 weeks old. We examined cardiac geometry and function by echocardiography, and histology and gene expression by high-density oligonucleotide arrays using Affymetrix U34 (Affymetrix, Santa Clara, CA, U.S.A.). Dahl salt-sensitive rats fed a high salt diet showed a marked increase in blood pressure and developed concentric hypertrophy at 11 weeks, followed by left ventricle dilation and congestive heart failure by 20 weeks after birth. Although both medications had only a mild antihypertensive effect, they strongly suppressed the development of cardiac hypertrophy, fibrosis and heart failure to the same extent. Gene expression pattern examined by Affymetrix GeneChip (Affymetrix) is quite different between the two drug groups, indicating that angiotensin II receptor blocker and angiotensin-converting enzyme inhibitor prevent heart failure by different mechanisms.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Benzimidazoles; Biphenyl Compounds; Disease Models, Animal; Echocardiography; Fibrosis; Gene Expression; Gene Expression Profiling; Heart Failure; Hypertension; Hypertrophy, Left Ventricular; Infusions, Parenteral; Male; Oligonucleotide Array Sequence Analysis; Organ Size; Rats; Rats, Inbred Dahl; Receptors, Angiotensin; Sodium Chloride, Dietary; Subcutaneous Tissue; Tetrazoles; Time Factors; Ventricular Function, Left

Continuous intra-arterial administration of a selective endothelin-converting enzyme (ECE) inhibitor CGS 35066 at a dose of 30 mg/kg decreased the mean arterial blood pressure (MABP) in conscious unrestrained normotensive rats and spontaneously hypertensive rats (SHRs). At that dose, the magnitude of the antihypertensive effects was greater in SHRs than in normotensive rats. Additional administration of an angiotensin-converting enzyme (ACE) inhibitor benazapril (lotensin) further reduced MABP in normotensive rats and completely blocked hypertension in SHRs. However, when the selective ECE inhibitor was subsequently removed, blood pressure was less inhibited in normotenive rats whereas it remained strongly inhibited in SHRs by the ACE inhibitor alone. These results imply that simultaneous treatment with benazepril and CGS 35066 gave additive antihypertensive effects in normotensive rats but not in SHRs, when both compounds were administered at a dose of 30 mg/kg. Our results suggest that: (i) the endothelin (ET) system together with the renin-angiotensin system contribute to the maintenance of blood pressure in normal healthy rats; (ii) while an ECE inhibitor acts as an antihypertensive agent on its own, the sole efficacy of ACE inhibitor at that dose is sufficient to block MABP without the participation of the ET system in SHR.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Aspartic Acid Endopeptidases; Benzazepines; Benzofurans; Blood Pressure; Drug Therapy, Combination; Endothelin-1; Endothelin-Converting Enzymes; Hypertension; Male; Metalloendopeptidases; Organophosphonates; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Topics: Amlodipine; Antihypertensive Agents; Benzazepines; Calcium Channel Blockers; Dose-Response Relationship, Drug; Drug Evaluation; Drug Therapy, Combination; Health Care Costs; Humans; Hypertension; Safety; Treatment Outcome

The effects of chronic treatment with losartan, an angiotensin II type 1 (AT1) receptor antagonist, and benazepril, an angiotensin converting enzyme (ACE) inhibitor, on target-organ damage and abnormal circadian blood pressure (BP) rhythm were compared in stroke-prone spontaneously hypertensive rats (SHRSP). Losartan and benazepril were given by intraperitoneal infusion for 3 weeks after 17 weeks of age to minimize any influence of their different pharmacokinetic properties. BP was continuously monitored by telemetrical method before treatment and at the end of the observation period. The left ventricular (LV) weight, 24-hour urinary albumin excretion (UalbV) and morphological changes in the kidney were observed. Losartan and benazepril (1, 3 and 10 mg/day) reduced BP and LV weight in a dose-dependent manner with good correlation between the effects. Losartan significantly improved UalbV in a dose-dependent manner, whereas benazepril was effective at only 10 mg/day. Renal morphological analysis showed that reduction of glomerulosclerosis and collagen fiber thickness was related to the effect on UalbV, but not to the antihypertensive effects. Losartan improved the shifted circadian BP rhythm towards the active phase in a dose-dependent manner, whereas the improvement caused by 1 and 3 mg/day of benazepril was less effective than the same dosage of losartan. These results suggest that both losartan and benazepril can reduce cardiac hypertrophy showing good correlation with their antihypertensive effects, but losartan, especially at a low dose, alleviates renal damage more effectively than benazepril, with its effect correlating well with improvement of the abnormal circadian BP rhythm in SHRSP. Thus, the protective effect against hypertensive target organ damage of the AT1 receptor antagonist seems to be more effective than that of ACE inhibitor.

Topics: Aldosterone; Animals; Antihypertensive Agents; Benzazepines; Blood Pressure; Cardiomegaly; Circadian Rhythm; Collagen; Heart Rate; Hypertension; Kidney; Losartan; Male; Organ Size; Rats; Rats, Inbred SHR; Renin; Urine

Recent hypertension trials have demonstrated the importance of achieving goal blood pressures to reduce the risk of target organ damage. In patients with moderate to severe hypertension, the use of high-dose monotherapy and/or combinations of drugs are necessary to achieve these goals. Fixed-dose combination products may be useful in these patients by reducing the number of daily doses required to control blood pressure.. The objective of the present study was to evaluate the efficacy and safety of a therapeutic interchange between high-dose calcium channel blocker therapy and a fixed-dose combination of amlodipine/ benazepril (Lotrel; Novartis Pharmaceuticals, USA) in patients with moderate to severe hypertension.. A total of 75 patients were switched from amlodipine (n = 25), felodipine (n = 25), and nifedipine-GITS (n = 25) to amlodipine/benazepril. Twenty-eight of the 75 patients (37%) were taking either a beta-blocker or a diuretic in addition to the high-dose calcium channel blocker prior to the switch. Blood pressure control, side effects and the cost of the therapeutic interchange were evaluated in the year following the therapeutic interchange.. Sixty-six of the 75 (88%) patients were successfully switched with maintenance of blood pressure control and without the development of new dose-limiting side effects. Reasons for treatment failure after the therapeutic interchange included loss of blood pressure control in five patients and the development of new dose-limiting side effects in four patients. These side effects included cough in three patients and rash in one patient. After accounting for differences in drug acquisition cost and costs related to the switch (clinic and emergency room and laboratory tests), a cost savings of $16030 for all 75 patients was realised in the first year. The per patient-per year cost savings was $214.. Our data indicate that a therapeutic interchange from selected high-dose calcium channel blockers to a fixed-dose combination of amlodipine/ benazepril can be successfully accomplished in the majority of patients.

Topics: Adult; Aged; Amlodipine; Antihypertensive Agents; Benzazepines; Blood Pressure; Calcium Channel Blockers; Costs and Cost Analysis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Felodipine; Female; Humans; Hypertension; Male; Middle Aged; Nifedipine; Treatment Outcome

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Asthma; Benzazepines; Gout; Health Maintenance Organizations; Humans; Hypertension; Male; Medical History Taking; Physical Examination

To evaluate the antihypertensive efficacy of angiotensin converting enzyme inhibitor (ACEI) benazepril in combination with AT1 receptor antagonist valsartan and their effect on left ventricular hypertrophy, renin angiotensin aldosterone system (RAAS) and endoxin in spontaneously hypertensive rat (SHR).. WKY control group (n = 6) and other 4 groups consisted of 24 SHR (14-week-old, male, n = 6): SHR control group, benazepril group, valsartan group, and combination drug therapy group. Systolic blood pressure (SBP) of SHR was measured at the beginning and at the end of 2, 4, 6, and 8 wk of drug intervention. Morphometric determination, renin activities, angiotensin II (Ang II), endoxin, and ATPase activity analysis were performed at the end of 8 week of drug intervention.. SBP, ratio of left ventricular mass (LVM), body weight (BW) (LVM/BW), and transverse diameter of myocardial cell (TDM) of SHR were remarkably decreased after drug intervention, and this decrease was most remarkable in the combination drug therapy group. Renin activities of plasma and myocardium were remarkably increased in drug intervention groups. The levels of Ang II in plasma and myocardium were remarkably increased in valsartan group, decreased in benazepril group and combination drug therapy group. Na(+)-K(+)-ATPase activities in myocardium were remarkably increased and the level of endoxin in myocardium were remarkably decreased as SBP decreased after drug intervention.. Both benazepril and valsartan can decrease SBP of SHR, and cause regression of ventricular hypertrophy. The efficacy of combination drug therapy group is most remarkable among all groups and avoids the side effects of induction of high Ang II levels in plasma and myocardium caused by long-term use of valsartan alone.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Benzazepines; Blood Pressure; Drug Therapy, Combination; Hypertension; Hypertrophy, Left Ventricular; Male; Random Allocation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Tetrazoles; Valine; Valsartan

Approximately 2% of pancreatitis in adults is drug induced. Although some angiotensin-converting enzyme (ACE) inhibitors have been associated with pancreatitis, to the knowledge of the authors this is the first reported case involving benazepril. This case report presents laboratory- and image-proven pancreatitis in a noninsulin dependent 70-year-old man. The patient took benazepril at three different times and experienced the same epigastric symptoms 30 min after each dose. Possible mechanisms are reviewed. Clinicians should strongly consider discontinuing ACE inhibitors, including benazepril, in patients with pancreatitis of no identifiable source.

Topics: Acute Disease; Aged; Amylases; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Diagnosis, Differential; Follow-Up Studies; Humans; Hypertension; Lipase; Male; Pancreatitis

Abnormalities in fibrinolysis, endothelial function, and glucose and lipid metabolism have been reported in hypertension. This study was conducted to examine the interrelationships between fibrinolytic factors, glucose and lipid metabolism, and endothelial function in hypertension. The effects of administering an angiotensin converting enzyme inhibitor, benazepril, were also examined. Blood levels of the following substances were measured in patients with borderline and mild hypertension (n=50, 51+/-19 years) and in age-matched controls (n=10): total cholesterol, triglycerides, tissue plasminogen activator activity and antigen, and plasminogen activator inhibitor type 1 activity and antigen. Insulin sensitivity was assessed by oral glucose tolerance test, and endothelial function was assessed by evaluating changes in diameter of the brachial artery during reactive hyperemia as observed by ultrasonography. Activities of tissue plasminogen activator and plasminogen activator inhibitor type 1 were both elevated in the hypertensive patients. Stepwise multiple regression analysis showed that plasminogen activator inhibitor type 1 antigen correlated with insulin sensitivity, total cholesterol levels, and triglycerides levels (P<.01). Endothelial function was negatively correlated with tissue plasminogen activator activity and antigen (P<.01). The chronic administration of benazepril (5-10 mg/d) for 20 weeks improved insulin sensitivity, endothelial function (6.6+/-3.4-->9.0+/-2.5%, P<.01), and tissue plasminogen activator activity and antigen. These results indicate that abnormalities in fibrinolysis are associated with endothelial dysfunction as well as disorders of glucose and lipid metabolism in patients with borderline and mild hypertension. The treatment of such patients with benazepril appeared to improve the impairment in fibrinolysis and endothelial dysfunction.

Topics: Adult; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Brachial Artery; Calcium Channel Blockers; Carotid Arteries; Cholesterol; Echocardiography; Endothelium, Vascular; Female; Fibrinolysis; Glucose Tolerance Test; Hemostasis; Humans; Hyperemia; Hypertension; Insulin; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Reference Values; Regression Analysis; Tissue Plasminogen Activator; Triglycerides

Chronic insulin infusion in rats increases mean arterial pressure (MAP) by a mechanism dependent on angiotensin II (Ang II). However, the fact that plasma renin activity (PRA) decreases with insulin infusion suggests that Ang II sensitivity is increased and that the parallel reduction in Ang II may partly counteract any hypertensive action of insulin. This study tested that hypothesis by clamping Ang II at baseline levels during chronic insulin infusion. Sprague-Dawley rats were instrumented with artery and vein catheters, and MAP was measured 24 hours per day. In seven angiotensin clamped rats (AC rats), renin-angiotensin II system activity was clamped at normal levels throughout the study by continuous intravenous infusion of the angiotensin-converting enzyme inhibitor benazepril at 5 mg/kg per day (which decreased MAP by 18+/-2 mm Hg) together with intravenous Ang II at 5 ng/kg per minute. Control MAP in AC rats after clamping averaged 99+/-1 mm Hg, which was not different from the 101+/-2 mm Hg measured before clamping Ang II levels. Control MAP in the 8 vehicle-infused rats averaged 105+/-2 mm Hg. A 7-day infusion of insulin (1.5 mU/kg per minute IV) plus glucose (20 mg/kg per minute IV) increased MAP in both groups of rats; however, the increase in MAP was significantly greater in AC rats (12+/-1 versus 5+/-1 mm Hg). This enhanced hypertensive response to insulin in AC rats was associated with a greater increase in renal vascular resistance (153+/-10% versus 119+/-6% of control) and a significant increase in renal formation of thromboxane (149+/-11% of control). Thus, decreased Ang II during insulin infusion limits the renal vasoconstrictor and hypertensive actions of insulin, and this may be caused, at least in part, by attenuation of renal thromboxane production.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Blood Pressure; Drug Synergism; Glucose; Hypertension; Insulin; Kidney; Male; Rats; Rats, Sprague-Dawley; Renal Circulation; Thromboxane B2; Vascular Resistance

Topics: Administration, Oral; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Captopril; Cross Reactions; Double-Blind Method; Drug Eruptions; Enalapril; Facial Dermatoses; Humans; Hypertension; Male; Middle Aged; Patch Tests

This study tested the dependence of insulin-induced hypertension in rats on a functional renin-angiotensin system. Rats were instrumented with chronic artery and vein catheters and housed in metabolic cages. After acclimation, 10 rats began receiving the angiotensin-converting enzyme inhibitor (ACEI) benazepril at 1.8 mg.kg-1.d-1 via a continuous intravenous infusion that was maintained throughout the study; 8 control rats received vehicle. Four days after starting ACEI or vehicle, all rats entered a 5-day control period that was followed by a 7-day insulin infusion at 1.5 mU.kg-1.min-1. Glucose was coinfused at 22 mg.kg-1.min-1 to prevent hypoglycemia. Insulin infusion in control rats increased mean arterial pressure (MAP; measured 24 h/d) from an average of 101 +/- 1 to 113 +/- 2 mm Hg on day 1; MAP averaged 110 +/- 1 mm Hg for the 7-day infusion period. Glomerular filtration rate decreased, although not significantly, from 2.7 +/- 0.1 to 2.1 +/- 0.2 mL/min on day 3. Chronic ACEI decreased baseline MAP from an average of 97 +/- 1 to 79 +/- 1 mm Hg and markedly attenuated the increase in MAP during insulin. MAP averaged 81 +/- 1 mm Hg for the 7-day period and increased significantly, to 85 +/- 2 mm Hg, only on day 3. Likewise, the tendency for glomerular filtration rate to decrease was blunted. These results indicate that insulin-induced hypertension in rats depends on angiotensin II and suggest that a reduction in glomerular filtration rate contributes to the shift in pressure natriuresis.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Benzazepines; Blood Pressure; Glomerular Filtration Rate; Hypertension; Insulin; Male; Natriuresis; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; Time Factors

The use of calcium channel blockers (CCBs) and angiotensin-converting enzyme (ACE) inhibitors has increased dramatically over the last 10 years and now accounts for 60% to 70% of all new antihypertensive prescriptions. Even though these two classes are efficacious, they are costly. Combined ACE inhibitor/CCB therapy (amlodipine-benazepril) was introduced in 1995. An analysis was done to assess the potential financial impact of substituting this agent for patients being treated with on ACE inhibitor/CCB combination. A pharmaceutical profile review of prescriptions during October 1995 was performed on 219 randomly selected patients enrolled in a Medicaid managed care program. Eighty-four profiles were analyzed; 24% of patients were on a combination ACE inhibitor/CCB regimen with an average monthly cost of $135. If the single agent amlodipine-benazepril with an average monthly cost of $45 (all strengths) was substituted, the savings would be considerable: $1080 per patient per year and $1,080,000 annualized for the calculated number of hypertensives on combination therapy in our network of 15,000 patients. Therapeutic substitution is one method of achieving cost containment in managed care. The cost differential between separately prescribed CCBs and ACE inhibitors and amlodipine-benazepril is significant. Compliance also should be enhanced as the patient would need to take only one pill daily. Once a patient has been maintained on a stable dose of a CCB/ACE inhibitor, substitution with amlodipine-benazepril should be considered.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Black People; Calcium Channel Blockers; Cost Control; Cost Savings; Drug Combinations; Drug Costs; Humans; Hypertension; Managed Care Programs; Medicaid; Patient Compliance; Therapeutic Equivalency; United States

The use of angiotensin-converting enzyme inhibitors during pregnancy has been associated with poor fetal outcomes, including oligohydramnios, renal tubular dysplasia, cranial malformations, and fetal death. A 35-year-old woman with chronic hypertension was treated with the angiotensin-converting enzyme inhibitor benazepril until 27 weeks' gestation, when severe oligohydramnios was noted. After hospitalization for bed rest, fetal surveillance, and discontinuation of the agent, amniotic fluid rapidly reaccumulated, and a healthy infant was delivered at term. Although the use of angiotensin-converting enzyme inhibitors should be avoided during pregnancy, patients whose fetuses are inadvertently exposed in utero need not be given a uniformly poor prognosis. Oligohydramnios induced by the use of angiotensin-converting enzyme inhibitors during pregnancy may be reversible if the agent is discontinued. This case underscores the need for obstetricians to review carefully the medication regimens of all pregnant women and to be familiar with generic and proprietary names of medications to avoid the use of potentially harmful agents during pregnancy.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Female; Humans; Hypertension; Oligohydramnios; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome

Authors examined the effects of benazepril, regarding the length of effectiveness by ambulatory blood pressure monitoring (ABPM), drug tolerable, and the compliance of patients in mild to moderate essential hypertension. 14 patients were treated with benazepril monotherapy. Six of them were newly diagnosed, and the rest had already been treated for hypertension. At the start, after six and 12 weeks, 24-hour monitoring was performed. Casual blood pressure (BP) measurements and detection of side-effects were also performed at 3rd and 9th-week. Prior the study the average daytime BP measured by ABPM was 149.1 +/- 7.7/96.6 +/- 4.7 mmHg. 10 mg of benazepril was first administered in the morning. By the end of the sixth week the average BP was significantly decreased (daily average: 139.1 +/- 9.9/88.2 +/- 7.6 mmHg). The daytime diastolic average BP of 8 patients was lower than 90 mmHg and the other's daily dose was raised to 20 mg. During the 12th-week we found optimal tension in 11 patients, while in two others there was also a significant decrease. The daily average BP was 134.7 +/- 7.5/85.6 +/- 6.6 mmHg. In comparison the data at the beginning of the study here was significant decrease in the 24-hour, daytime and night-time BP, in the hypertension time-index and the hyperbaric impact, both in systolic and diastolic levels. During the 12th-week period the diurnal index was unchanged. The early morning BP decreased by the end of the 3rd month from 148.6 +/- 14.1/98.5 +/- 11.7 mmHg to 135.2 +/- 13.5/93.4 +/- 11.2 mmHg. Sustained side-effect did not occur. The patient's compliance to benazepril was excellent. Authors conclude that benazepril monotherapy lowered in 92.8%, and normalized in 78.5% the blood pressure of patients suffering from mild to moderate essential hypertension. The unchanged diurnal index, and the decrease in the early morning blood pressure suggest the 24-hour effect of benazepril.

Topics: Adult; Aged; Antihypertensive Agents; Benzazepines; Blood Pressure Monitoring, Ambulatory; Female; Humans; Hypertension; Male; Middle Aged; Severity of Illness Index

This study compared the effect of benazepril, an angiotensin converting enzyme inhibitor ([S-(R*,R*)]-3-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-2,3,4,5- tetrahydro-2-oxo) to valsartan, an angiotensin AT1 receptor antagonist ((S)-N-valeryl-N-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]-methyl-valin e) on glucose metabolism and plasma lipid levels in 11- to 12-week-old conscious spontaneously hypertensive rats. Intraperitoneal infusion of benazepril or valsartan at 1, 3 and 10 mg/kg/day produced dose-related reductions in systolic blood pressure after 12 weeks which were not significantly different from each other. During the infusion, valsartan-treated animals gained weight at the same rate as controls, but all infusion rates of benazepril significantly suppressed normal weight gain, despite both compounds having similar antihypertensive effects. At the end of the 12-week treatment period, benazepril (3 and 10 mg/kg/day) significantly increased glucose disposal but did not significantly affect insulin disposal in insulin/glucose tolerance tests. In contrast, none of the infusion rates of valsartan significantly affected glucose or insulin disposal. Finally, compared to controls benazepril and valsartan were without effect on the fasting basal plasma concentrations of glucose, insulin, triglycerides, total cholesterol and K+. The results demonstrate that angiotensin converting enzyme inhibition and angiotensin AT1 receptor antagonism have similar antihypertensive effects, but express differences on body weight gain and insulin-stimulated glucose disposal in the conscious spontaneously hypertensive rat.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Benzazepines; Blood Glucose; Blood Pressure; Body Weight; Drug Tolerance; Glucose Intolerance; Hypertension; Insulin Resistance; Lipids; Rats; Rats, Inbred SHR; Tetrazoles; Valine; Valsartan

Endothelial regulation of peripheral vascular resistance is impaired in hypertension. We studied the effects of different antihypertensive therapies on endothelial function in perfused mesenteric resistance arteries. Spontaneously hypertensive rats (SHR) aged 7 weeks were treated with either the nonpeptidic angiotensin II (AII) receptor antagonist CGP 48369, the angiotensin-converting enzyme (ACE) inhibitor benazepril HCl, or the calcium antagonist nifedipine (each 10 mg/kg/day orally, p.o.) for 8 weeks. All forms of therapy inhibited the increase in systolic blood pressure (SBP) to a comparable degree (18-23 mm Hg) and reduced but did not normalize medial hypertrophy in SHR. Changes in intraluminal vascular diameter to acetylcholine (ACh), norepinephrine (NE), and endothelin-1 (ET-1) were measured. Impaired endothelium-dependent relaxations to intraluminal ACh improved or normalized with all therapies, whereas the response to extraluminal ACh (which was unimpaired in SHR) remained unaffected. The endothelium-dependent inhibition of contractions to NE was lost in untreated SHR and improved or restored by antihypertensive therapy. In SHR, the sensitivity but not the maximal response of vascular smooth muscle (VSM) to ET-1 was paradoxically decreased. Antihypertensive therapy with CGP 48369, nifedipine, or benazepril HCl restored or increased the sensitivity to ET-1. Thus, chronic blockade of the renin-angiotensin system or voltage-operated calcium channels reduces BP and improves endothelial dysfunction in the resistance circulation of SHR. This may contribute to normalization of peripheral vascular resistance during antihypertensive treatment and improve local blood flow to vital organs.

Topics: Acetylcholine; Angiotensin II; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Benzazepines; Blood Pressure; Disease Models, Animal; Endothelins; Endothelium, Vascular; Hypertension; In Vitro Techniques; Male; Mesenteric Arteries; Muscle Contraction; Muscle Relaxation; Muscle, Smooth, Vascular; Nifedipine; Norepinephrine; Potassium Chloride; Pyrimidines; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Angiotensin; Tetrazoles; Vascular Resistance

The effect of the angiotensin I-converting enzyme (ACE) inhibitor benazepril (55 mg/kg orally) on the preservation of cardiac performance in diabetic-hypertensive Dahl S rats was investigated. Diabetes mellitus was produced by streptozotocin. Fasting (4-h) blood glucose levels were 279 +/- 50 mg/dL in diabetic Dahl salt-sensitive v 79 +/- 5 mg/dL in nondiabetic Dahl salt-sensitive rats. Cardiac performance was determined at the end of 8 weeks in an isolated perfused working heart apparatus. Peak left ventricular pressure (LVPmax), left ventricular peak negative dP/dt, and coronary flow were depressed in diabetic Dahl S rats (P < or = .05 v control). These deficits in cardiac function were not observed in diabetic Dahl S rats chronically treated with benazepril. The beneficial effects of benazepril apparently were independent of systolic blood pressure reduction. Although plasma ACE activity was increased in diabetic Dahl S rats, plasma renin activity was reduced. This suggests that the beneficial effects of ACE inhibition may be due to an effect upon the kinin system rather than the renin-angiotensin system. The benazepril-associated preservation of cardiac function in this study suggests that ACE inhibitors may be beneficial in the treatment of diabetic heart disease.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Blood Glucose; Blood Pressure; Coronary Circulation; Diabetes Mellitus, Experimental; Hypertension; Insulin; Male; Rats; Rats, Inbred Strains; Renin; Streptozocin; Ventricular Function, Left

To assess the effects of benazepril (ACE inhibitor) on arterial blood pressure (ABP) and left ventricular mass index (LVMI).. Nineteen patients (7 men, 12 women) with mean age 38.2 +/- 10.2 years, with mild to moderate hypertension were evaluated. Besides raised blood pressure, the necessary inclusion criterion was the presence of left ventricular hypertrophy detected by echocardiogram. After a wash-out period, all patients were given placebo followed by the active drug benazepril at a dose of 10 mg once a day. For those patients who did not achieve a satisfactory control of the blood pressure (BP) 25 mg of chlorthalidone was added. All patients underwent 180 days of benazepril treatment.. The ABP was gradually controlled as follow: at seated position the systolic BP changed from 156.05 +/- 5.07 mmHg to 129 +/- 3.74 mmHg (p < 0.001) and the diastolic BP from 99.74 +/- 1.59 mmHg to 81.8 +/- 2.27 mmHg (p < 0.001). At orthostatic position the systolic BP changed from 156.9 +/- 5.35 mmHg to 124.28 +/- 5.33 mmHg (p < 0.001) and the diastolic BP from 101.7 +/- 1.34 to 81.36 +/- 2.81 (p < 0.001). The heart rate did not change significantly during the study. The LVMI decreased significantly from 182.4 +/- 9.2g/m2 to 122.6 +/- 4.2g/m2 (p < 0.001).. Our data revealed that 100% of the patients achieved satisfactory degrees of LVMI regression and in 34% there was a normalization of it.

Topics: Administration, Oral; Antihypertensive Agents; Benzazepines; Blood Pressure; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Benzazepines; Celiprolol; Collagen; Hypertension; Hypertrophy, Left Ventricular; Male; Proteins; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA; Verapamil

One of the functions of the sympathetic nervous system is to produce a short-term increase in blood pressure. It might be thought, therefore, that antihypertensive drugs which interfere with the functioning of the sympathetic nervous system (e.g. betablockers) would reduce blood pressure variability over 24 h whereas those that act independently of it (e.g. ACE inhibitors) would not. Two groups of 10 hypertensives underwent noninvasive 24-h blood pressure monitoring before and after antihypertensive treatment with a betablocker (atenolol) and an ACE inhibitor (benazepril) respectively. Blood pressure variability was measured by the variability coefficient (standard deviation/mean). Atenolol induced a non-statistically significant decrease in blood pressure variability, whereas benazepril caused a statistically significant increase in systolic blood pressure variability. Therefore, we conclude that the evaluation of ACE-inhibitor therapeutic effect on blood pressure by the "casual" measurement can be misleading in judging the efficacy of such drugs.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atenolol; Benzazepines; Blood Pressure; Blood Pressure Monitors; Circadian Rhythm; Drug Evaluation; Female; Humans; Hypertension; Male; Middle Aged

This study was undertaken to determine the biochemical and left ventricular functional changes associated with reversal of left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHR).. Male SHR and normotensive Wistar-Kyoto (WKY) rats, aged 19 weeks, were treated for 3 weeks with vehicle, amlodipine (10 mg/kg), benazepril (10 mg/kg) or the combination of both agents (4 mg/kg amlodipine and 4 mg/kg benazepril). Left ventricular function was assessed while blood was infused rapidly, at pharmacologically reduced and pretreatment mean arterial pressure (MAP).. All treatments reduced MAP and left ventricular mass significantly in SHR. Myocardial protein, RNA and myocardial collagen content were reduced proportionately in all treatment groups in SHR, but not in WKY rats. DNA remained unchanged in all groups. Increased right ventricular mass was produced by amlodipine in both SHR and WKY rats (SHR +11.3%; WKY +9.8%), but this was prevented by cotreatment with benazepril. Right ventricular protein and collagen increased significantly with amlodipine in SHR but not WKY rats, and there were no changes in right ventricular RNA and DNA contents in either strain. Amlodipine improved, benazepril impaired and the combination of both agents maintained left ventricular pumping ability when pressure was increased abruptly to pretreatment levels in WKY rats. In contrast, when afterload was increased abruptly in SHR to pretreatment levels, neither amlodipine nor benazepril affected pumping ability, although it was enhanced by the combination.. These data demonstrate that amlodipine, benazepril and their combination reduced left ventricular mass in SHR. This reversal of LVH was associated with proportional reductions in mycotic protein, RNA and collagen, but not DNA. Therefore, it seems unlikely that LVH reversal with these agents was associated with increased fibrous tissue or impaired left ventricular performance. Finally, addition of the angiotensin converting enzyme inhibitor prevents the increase in right ventricular mass produced by the calcium antagonist.

Topics: Amlodipine; Animals; Benzazepines; Collagen; Drug Combinations; Hemodynamics; Hypertension; Hypertrophy, Left Ventricular; Male; Myocardium; Nucleic Acids; Proteins; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Ventricular Function, Left

Topics: Antihypertensive Agents; Arteriosclerosis; Benzazepines; Humans; Hypertension

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Humans; Hypertension

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Humans; Hypertension

We investigated the long-term effects of benazepril, a new non-sulfydryl angiotensin converting enzyme inhibitor, on ambulatory blood pressure (BP) and left ventricular (LV) anatomy and function in 13 never treated hypertensive patients (mean age 55 years--SD 9). Non-invasive ambulatory BP monitoring (Spacelabs 90202, a reading every 15 min for 24 hours) and standard and pulsed Doppler echocardiography were performed basally and after 12 months of therapy. Echocardiography was performed also at the end of 18th month of treatment. Eleven patients required a single daily dose of benazepril 10 (n = 9) or 20 (n = 2) mg, and two patients of 20 mg plus chlorthalidone 25 mg, to achieve clinical BP control. Average 24 h systolic/diastolic BP was 156/100 mmHg (SD 17/5) basally and 144/90 mmHg (SD 16/7) at the end of the 12th month of treatment (all p less than 0.01), LV mass index was 133 g/m2 basally and 113 g/m2 at the 12th month (p less than 0.01), early transmitral flow velocity (peak E) was 0.43 m/s (SD 0.11) basally and 0.62 (SD 0.13) m/s at the 12th month (p less than 0.01), and late transmitral flow velocity (peak A) did not change [0.67 (SD 0.10) m/s basally and 0.64 (SD 0.11) m/s at the 12th month]. Peak A/peak E ratio decreased from 1.69 (SD 0.57) to 1.31 (SD 0.37) (p less than 0.01). Peak aortic velocity, aortic acceleration time and aortic acceleration did not change. The per cent reduction of LV mass index was more closely related to the reduction of average 24 h systolic (r = 0.66, p = 0.013) and diastolic (r = 0.72, p = 0.005) BP than to the reduction of casual systolic (r = 0.37, p = NS) and diastolic (r = 0.42, p = NS) BP. None of the echocardiographic indices changed between the 12th and 18th month of treatment. In a control group of 13 age- and sex-matched healthy normotensive volunteers who underwent 24 h ambulatory BP monitoring and echocardiography twice, 12 months apart, there were no statistically significant BP or echographic changes. In summary, long-term antihypertensive treatment with benazepril provided and effective 24 h BP control, associated with regression of LV hypertrophy and improvement in LV diastolic filling, without changes in LV systolic function.

Topics: Ambulatory Care; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Blood Pressure Determination; Cardiomegaly; Echocardiography, Doppler; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Monitoring, Physiologic

Topics: Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Bridged Bicyclo Compounds; Drug Interactions; Fosinopril; Heart Failure; Humans; Hypertension; Prodrugs; Proline; Ramipril

To study the effects of a novel angiotensin I converting enzyme inhibitor (ACEI) on hypertension-induced cardiac hypertrophy, benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4) at the dose of 3 and 10 mg/kg/d p.o. was administered to spontaneously hypertensive rats from 4 to 16 weeks of age. In addition to suppression of developing blood pressure, benazepril hydrochloride reduced both the wet weights of whole heart and left ventricle dose-dependently and significantly. Benazepril hydrochloride had no effect on hydroxyproline concentration and content or protein concentration in the left ventricle, whereas is reduced the total protein content dose-dependently. Serum ACE activity was significantly reduced at 10 mg/kg/d of benazepril hydrochloride, but renin activity, aldosterone and noradrenaline concentration in serum were not changed. From the microscopic findings of the left ventricle, benazepril hydrochloride reduced the myocardial hypertrophy significantly. From these results, benazepril hydrochloride seems to suppress the increase in volume load by acting through the renin-angiotensin-aldosterone system, and dose not seem to cause a significant reflex of catecholamine which often occurs with peripheral vessels dilation. Thus, benazepril hydrochloride may be expected to suppress cardiac hypertrophy in patients with hypertension.

Topics: Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Biomarkers; Blood Pressure; Cardiomegaly; Heart Rate; Hydroxyproline; Hypertension; Male; Muscle Proteins; Myocardium; Norepinephrine; Organ Size; Rats; Rats, Inbred SHR; Renin

Single or repeated administration of benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4), a novel angiotensin I converting enzyme inhibitor, (0.3-10 mg/kg p.o.) caused significant antihypertensive effects in renal and spontaneously hypertensive rats (SHR). The antihypertensive effects of benazepril hydrochloride was about 3 times as potent as that of captopril in these models. Single administration (0.3-3 mg/kg p.o.) of benazepril hydrochloride and enalapril maleate showed an equipotent antihypertensive effect in SHR. Benazepril hydrochloride (3-30 mg/kg p.o.), however, showed no clear effect on the blood pressure and heart rate in normotensive or DOCA/salt hypertensive rats.

Topics: Administration, Oral; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Benzazepines; Captopril; Desoxycorticosterone; Enalapril; Hypertension; Hypertension, Renovascular; Male; Rats; Rats, Inbred SHR; Rats, Inbred Strains

Seventeen essential hypertensive patients with normal renal function were treated with a new non-sulphydryl orally active angiotensin converting enzyme (ACE) inhibitor, benazepril, 10 mg given once or twice daily, according to diastolic blood pressure levels, for 6 weeks. In all patients, changes in blood pressure, systemic and renal hemodynamics, plasma renin activity and urinary aldosterone and albumin excretions were assessed at the end of a 2-week placebo run-in period and at the end of the study. Benazepril monotherapy controlled blood pressure well. No changes in cardiac output, heart rate or stroke volume were observed, while peripheral vascular resistance was significantly decreased (-11%, P less than 0.05). Plasma volume was unaltered. The glomerular filtration rate was stable, but effective renal plasma flow was increased because of the marked reduction in renal vascular resistance (-35%) and, therefore, the filtration fraction was decreased. Urinary albumin excretion remained unchanged. A significant increase in plasma renin activity (P less than 0.001) and a decrease in urinary aldosterone excretion were seen. No side effects were observed during the treatment period. In conclusion, our results suggest that benazepril alone is an effective antihypertensive agent in patients with essential hypertension. The blood pressure lowering effect is due mainly to systemic vasodilation and is observed up to 24 h after administration of the drug. The vasodilation appears to be more consistent in the renal than in the systemic circulation.

Topics: Adult; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Drug Evaluation; Electrolytes; Female; Hemodynamics; Humans; Hypertension; Kidney; Male; Middle Aged; Renin

1. Urinary albumin excretion and the effect of an acute oral protein load (a meat meal) on glomerular filtration rate ('renal functional reserve') were evaluated in 15 essential hypertensive patients with preserved renal function and compared with 12 normal subjects. 2. Seven patients had microalbuminuria (greater than 30 mg/day) that was not correlated with blood pressure values. 3. After an oral protein load, an average increase of 20% in glomerular filtration rate (from 91 +/- 19 to 110 +/- 27 ml min-1 1.73 m-2 was found in the hypertensive patients. This change was not statistically different from that observed in normal controls (from 102 +/- 7 to 124 +/- 9 ml min-1 1.73 m-2). The glomerular response in hypertensive patients was independent of age, duration of hypertension, blood pressure, plasma renin activity, urinary albumin excretion and retinal vascular alterations. 4. All patients were re-evaluated after 6 weeks treatment with a new orally active angiotensin-converting enzyme inhibitor, benazepril. Systolic, diastolic and mean blood pressures were lowered in all the patients, but the drug did not affect the glomerular response to acute protein ingestion or the magnitude of urinary albumin excretion. 5. The findings of a normal 'renal functional reserve' and a lack of change in both urinary albumin excretion and the glomerular response after angiotensin-converting enzyme inhibition cast doubt on the existence of increased intraglomerular pressure in hypertensive patients.

Topics: Adult; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Female; Glomerular Filtration Rate; Humans; Hypertension; Male; Middle Aged; Renin-Angiotensin System

This article emphasizes the importance of testing baroreceptor and cardiopulmonary receptor control of circulation during angiotensin-converting enzyme (ACE) inhibitor treatment in hypertensives, because removal of angiotensin II-dependent stimulation of the sympathetic nervous system could impair reflex blood pressure homeostasis. In essential hypertensive subjects, the sympathetic vasoconstriction that occurs in skeletal muscle after deactivation of cardiopulmonary receptors was reduced after short-term or prolonged administration of the ACE inhibitor, captopril. However, another sympathetic target of the cardiopulmonary reflex, that is, renin release, was unaltered by both short-term and prolonged administration of captopril. Furthermore, the blood pressure and heart rate influences of arterial baroreceptors were preserved or even enhanced after administration of captopril. Thus important reflex mechanisms for cardiovascular homeostasis are not adversely affected by ACE inhibition, which preserves blood pressure levels during gravity challenges or exercise. Preliminary data suggest that this may be even more evident for benazepril.

Topics: Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Blood Volume; Captopril; Humans; Hypertension; Pressoreceptors; Reflex; Renin-Angiotensin System; Sympathetic Nervous System; Vascular Resistance; Vasodilation

Nine hypertensive patients with mild to moderate renal dysfunction were entered into a protocol to assess the blood pressure, humoral and renal effects of the angiotensin converting enzyme inhibitor, Benazepril (CGS14824A, 2 to 20 mg twice daily) in patients with hypertension and moderate renal insufficiency (mean creatinine clearance 56 ml/min/1.73 m2). Specifically monitored, prior to and following 12 weeks of Benazepril monotherapy, were plasma renin activity and plasma aldosterone, the clearances of creatinine, Tc99m-diethylenetriaminepentaacetic acid (TC99m-DTPA) and para-amino-hippurate, and the 24-hour urinary excretion of protein. Blood pressure was well controlled. Plasma renin activity was stimulated, and plasma aldosterone was suppressed. Mean serum potassium increased from 3.9 to 4.2 mEq/L. Benazepril monotherapy had no adverse renal hemodynamic effect. Benazepril appears to be an effective antihypertensive agent in hypertensive patients with moderately impaired renal function.

Topics: Aged; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Kidney Diseases; Male; Middle Aged; Potassium; Renin

The preparation of a series of 3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine-1-acetic acid derivatives 5a-y by reductive amination of 2,3,4,5-tetrahydro-1H-1-benzazepine-2,3-dione (7) with L-amino acid derivatives is described. The compounds were tested for inhibition of angiotensin converting enzyme. The structure-activity profile of the series is discussed. Compound 5a was especially potent when tested in dogs for inhibition of angiotensin I pressor response, having an ID50 = 0.07 mg/kg po.

Topics: Amino Acids; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Blood Pressure; Chemical Phenomena; Chemistry; Dogs; Hypertension; Rats; Rats, Inbred SHR; Structure-Activity Relationship