benazepril and Diabetes-Mellitus--Type-2

The therapeutic advantage of the long acting ACE-inhibitor benazepril in a 12 weeks intervention period on 23 diabetic (3 IDDM, 20 NIDDM) patients with essential hypertension was studied. Participants-giving informed consent before beginning the study-on the base of repeated casual blood pressure measurements were divided into "slightly" (n = 8) and "moderately" (n = 15) hypertonic groups. Type of diabetes, time elapsed since its manifestation, actual antidiabetic therapy, period of existence of the hypertension (newly discovered vs known and treated for a time) were independent from the point of view of entering the study. Initial dose of benazepril was 5-10 mg/day depending on the blood pressure level, followed by a stepwise dose elevation according to the control investigations (at weeks 2, 4, 8 and 12 casual blood pressure control, at weeks 4 and 12 ambulantory blood pressure monitoring, ABPM as well) to a maximal daily dose of 20 mg. In the majority of patients benazepril was given in a morning single dose, in some cases because of a better tolerability divided into two parts. 20 patients received benazepril in monotherapy, 3 patients combined with other antihypertensive preparations. Parameters indicating severity of hypertension-hypertonic time index, hyperbaric impact-showed significant improvement already at week 4 when analysed in the total of patients and the moderately hypertonic group respectively. As a tendence the same was observed also in the slightly hypertonic group. No remarkable side effects, or alterations of the metabolic state and in the investigated laboratory parameters appeared. Based on these results benazepril is an effective choice in the treatment of diabetic hypertensive patients.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Middle Aged

Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) prevent microalbuminuria in normoalbuminuric type 2 diabetic patients. We assessed whether combined therapy with the 2 medications may prevent microalbuminuria better than ACE inhibitor or ARB monotherapy.. VARIETY was a prospective, randomized, open-label, blinded endpoint (PROBE) trial evaluating whether, at similar blood pressure (BP) control, combined therapy with benazepril (10 mg/day) and valsartan (160 mg/day) would prevent microalbuminuria more effectively than benazepril (20 mg/day) or valsartan (320 mg/day) monotherapy in 612 type 2 diabetic patients with high-normal albuminuria included between July 2007 and April 2013 by the Istituto di Ricerche Farmacologiche Mario Negri IRCCS and 8 diabetology or nephrology units in Italy. Time to progression to microalbuminuria was the primary outcome. Analyses were intention to treat. Baseline characteristics were similar among groups. During a median [interquartile range, IQR] follow-up of 66 [42 to 83] months, 53 patients (27.0%) on combination therapy, 57 (28.1%) on benazepril, and 64 (31.8%) on valsartan reached microalbuminuria. Using an accelerated failure time model, the estimated acceleration factors were 1.410 (95% CI: 0.806 to 2.467, P = 0.229) for benazepril compared to combination therapy, 0.799 (95% CI: 0.422 to 1.514, P = 0.492) for benazepril compared to valsartan, and 1.665 (95% CI: 1.007 to 2.746, P = 0.047) for valsartan compared to combination therapy. Between-group differences in estimated acceleration factors were nonsignificant after adjustment for predefined confounders. BP control was similar across groups. All treatments were safe and tolerated well, with a slight excess of hyperkalemia and hypotension in the combination therapy group. The main study limitation was the lower than expected albuminuria at inclusion.. Risk/benefit profile of study treatments was similar. Dual renin-angiotensin system (RAS) blockade is not recommended as compared to benazepril or valsartan monotherapy for prevention of microalbuminuria in normoalbuminuric type 2 diabetic patients.. EudraCT 2006-005954-62; ClinicalTrials.gov NCT00503152.

Topics: Aged; Albuminuria; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Valsartan

To evaluate whether angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) combination therapy is more nephroprotective than ACE inhibitor or ARB monotherapy in people with type 2 diabetes and overt nephropathy.. In this prospective, randomized, open, blind-endpoint phase III trial sponsored by the Italian Drug Agency, 103 consenting patients with type 2 diabetes, aged >40 years, with serum creatinine levels 159 to 309 μmol/L, spot morning urinary albumin-creatinine ratio > 1000 mg/g (or > 500 mg/g in those on ACE inhibitor or ARB therapy at inclusion) were stratified by centre and randomized to 4.5-year treatment with valsartan 320 mg/d (n = 36), benazepril 20 mg/d (n = 34) or halved doses of both medications (n = 33). The primary endpoint was end-stage renal disease (ESRD). Modified intention-to-treat analyses were performed.. Recruitment took place between June 2007 and February 2013 at 10 centres in Italy and one in Slovenia. A total of 77 participants completed the study and 26 were prematurely withdrawn. During a median (interquartile range) of 41 (18-54) months, 12 participants on benazepril (35.3%) and nine on combination therapy (27.3%) progressed to ESRD, versus five on valsartan (13.9%). Differences between benazepril (hazard ratio [HR] 3.59, 95% confidence interval [CI] 1.25-10.30; P = 0.018) or combination therapy (HR 3.28, 95% CI 1.07-10.0; P = 0.038) and valsartan were significant, even after adjustment for age, gender and baseline serum creatinine, systolic blood pressure and 24-hour proteinuria (HR 5.16, 95% CI 1.50-17.75, P = 0.009 and HR 4.75, 95% CI 1.01-22.39, P = 0.049, respectively). Adverse events were distributed similarly among the groups.. In people with type 2 diabetes with nephropathy, valsartan (320 mg/d) safely postponed ESRD more effectively than benazepril (20 mg/d) or than halved doses of both medications.

Topics: Adult; Aged; Benzazepines; Biomarkers; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug Therapy, Combination; Female; Humans; Italy; Kidney Function Tests; Male; Middle Aged; Slovenia; Treatment Outcome; Valsartan

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

Brain-derived neurotrophic factor (BDNF) is associated with sympathetic activation. However, the effects of BDNF on diabetic nephropathy are unknown. The aim of this study was to assess the estimated glomerular filtration rates (eGFRs) and changes in serum BDNF levels in type 2 diabetic subjects treated with antihypertensive medications.. In this randomized, double-blind clinical trial, type 2 diabetic subjects with hypertension were assigned to either the benazepril/amlodipine or valsartan/hydrochlorothiazide treatment groups for a 16-week period. The post hoc analyses were based on increased or decreased serum BDNF levels.. Of the 153 enrolled subjects, the changes in eGFR were significantly and inversely correlated with those in BDNF in the 76 subjects treated with valsartan/hydrochlorothiazide (r = -0.264, P = 0.021) but not in the 77 subjects treated with benazepril/amlodipine (r = -0.025, P = 0.862). The 45 subjects with increased BDNF following valsartan/hydrochlorothiazide treatment exhibited a significantly reduced eGFR (-8.8 ± 14.9 mL/min/1.73 m(2); P < 0.001). Multivariate regression analysis revealed that increased serum BDNF represents an independent factor for reduced eGFR (95% confidence interval between -0.887 and -0.076, P = 0.020).. Increased serum BDNF is associated with reduced eGFR in type 2 diabetic subjects treated with valsartan/hydrochlorothiazide but not with amlodipine/benazepril.

Topics: Aged; Amlodipine; Antihypertensive Agents; Benzazepines; Brain-Derived Neurotrophic Factor; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glomerular Filtration Rate; Humans; Hydrochlorothiazide; Male; Middle Aged; Valsartan

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

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 observe the effect of combined therapy with Bailing Capsule (BC) and benazepril on the levels of urinary albumin excretion rate (UAER) and C-reactive protein (CRP) for exploring its protective effect on early diabetic nephropathy.. Sixty patients with early diabetic nephropathy were randomly assigned to the control group treated by benazepril alone, and the treated group treated by BC and benazepril, and the treatment lasted for 16 weeks. The changes of UAER and CRP levels were measured to estimate the protective effect of the combined therapy.. Levels of 24h urinary protein, UAER, CRP were (0.85 +/- 0.32) g/24 h, (83.34 +/- 38.27) microg/min, (2.67 +/- 1.72) mg/L before treatment in the control group, and (0.43 +/- 0.17) g/24 h, (71.22 +/- 31.12) microg/min, (1.05 +/- 0.78) mg/L after treatment and they were (0.87 +/- 0.31) g/24 h, (81.59 +/- 35.69) microg/min, (2.55 +/- 1.66) mg/L before treatment in treated group, and (0.25 +/- 0.29) g/24 h, (57.32 +/- 31.11) microg/min, (0.49 +/- 0.38) mg/L after treatment respectively, all of them decreased after treatment in both groups, showing significant differences as compared with those before treatment (P<0.05, P< 0.01), and the reduction in the treated group was more significant (P<0.01); meanwhile, levels of serum creatinine, fasting blood glucose and HbA1c had somewhat decrease, showing no statistical difference with those before treatment (P >0.05).. Combined use of BC and benazepril could significantly lower the UAER and CRP levels in patients with early diabetic nephropathy to alleviate the renal impairment, showing an effect better than that of using benazepril alone.

Topics: Adult; Aged; Albuminuria; Benzazepines; C-Reactive Protein; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Humans; Male; Middle Aged; Phytotherapy

Diabetic nephropathy management should include the use of an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker with additional antihypertensive medications to reduce proteinuria and cardiovascular events. Some studies suggest that adding a nondihydropyridine rather than a dihydropyridine calcium channel blocker (CCB) may more effectively lower proteinuria. We hypothesized that a trandolapril/verapamil SR (T/V) fixed-dose combination (FDC) was superior to a benazepril/amlodipine (B/A) FDC for reducing albuminuria in 304 hypertensive diabetic nephropathy patients when treated for 36 weeks. No statistically significant differences were observed between groups in the primary end point; adjusted percentage change in urinary albumin/creatinine ratio (UACR), which increased (mean T/V, 29.29%; mean B/A, 8.49%; difference, 20.80%; P=.34); or in change in absolute UACR, which decreased (mean [g/g] T/V, -0.11; mean [g/g] B/A, -0.08; difference -0.03; P=.78). There were significant reductions in log UACR (mean change in T/V, -0.28; P<.01; mean change in B/A, -0.31; P<.001) and diastolic blood pressure in both groups and in systolic blood pressure in the B/A group. T/V was not superior to B/A for reducing UACR. Both ACEI/CCB FDCs may reduce albuminuria; in the case of T/V, this appears to be independent of systolic blood pressure reduction in patients who had previously been treated and had baseline blood pressure levels of 142/77 mm Hg.

Topics: Aged; Albuminuria; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug Synergism; Drug Therapy, Combination; Female; Humans; Indoles; Male; Middle Aged; Prospective Studies; Proteinuria; Treatment Outcome; Verapamil

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

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

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

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

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

Microalbuminuria (MA) is associated with increased cardiovascular risk and lipid abnormalities in people with type 2 diabetes. ACE inhibitors and calcium channel blockers (CCBs) reduce MA and are neutral on total cholesterol and triglycerides. The effect of ACE inhibitors and CCBs on lipid subfractions such as Lp(a), apolipoprotein (apo) A1, apo B, and others, however, is unclear. The current study tests the hypothesis that a fixed-dose combination of an ACE inhibitor, benazepril (B) with the dihydropyridine CCB, amlodipine (A), will further reduce arterial pressure and reduce atherogenic lipid fractions compared to either agent alone.. A multicentre, randomised, open-label, parallel group design was used to study 27 participants with type 2 diabetes. Measurements for total cholesterol, high- and low-density lipoprotein (HDL and LDL), triglycerides, apo A1, apo B, Lp(a), MA, arterial pressure and creatinine clearance were obtained at baseline and at 12-week intervals during the 36 week study.. Arterial pressure was significantly reduced at 36 weeks in all three groups (P = 0.0078 for A, P = 0.0039 for B, and P = 0.0313 for A+B). MA was lowered in all groups with relatively greater reductions in the B (P < 0.05) and A+B groups (P < 0.03) vs A. An increase in mean HDL-cholesterol from baseline was noted in the B and A+B groups; P < 0.05), but not in the A group. A trend was also observed between the rise in HDL-cholesterol and the reduction in MA in the B and A+B groups. Additionally, only the B group exhibited a decrease in the median value of Lp(a) (P < 0.05).. These data support the concept that ACE inhibition with B reduces the atherogenic profile by decreasing Lp(a) and increasing HDL-cholesterol, the latter being correlated with reductions in MA. While A+B exhibited similar trends in lipid subfractions and MA as B, this group had the greatest reduction in systolic blood pressure of the three groups. Thus, use of A+B offers the benefits of a decreased atherogenic profile with a higher probably of achieving goal blood pressure as recommended by national guidelines.

Topics: Aged; Albuminuria; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Apolipoproteins; Apoprotein(a); Benzazepines; Calcium Channel Blockers; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Dihydropyridines; Female; Humans; Lipoprotein(a); Male; Middle Aged; Pilot Projects; Triglycerides

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

Although post exercise proteinuria has long been known, its exact pathophysiology is unclear. Our objective was to determine whether long-term angiotensin converting enzyme (ACE) inhibition by different ACE inhibitors had an influence on post exercise proteinuria. We studied 14 patients who also had mild, chronic proteinuria caused by diabetes mellitus or chronic glomerulonephritis. We compared changes both in chronic (baseline) and post exercise proteinuria, during and after treatment with three different ACE inhibitors, with appropriate washout periods for the three drugs to all 14 patients. Proteinuria (mg/24 hours +/- SD), prior to the treatment was 682 +/- 92. Proteinuria after treatment for 30 days with benazepril was 464.4 +/- 82.6 (p < 0.001), with enalapril: 477.1 +/- 105.5 (p < 0.001), and captopril: 504.7 +/- 100.1 (p < 0.001). Proteinuria three days after discontinuing the treatment with benazepril was 532.4 +/- 113.5, (p < 0.01), with enalapril: 561.3 +/- 128.5, (p < 0.01), and with captopril: 620.8 +/- 101.8, p = n.s. Post exercise proteinuria prior to treatment (mg/min. +/- SD) was: 1.38 +/- 0.32, vs. after a 30-day treatment period with benazepril: 0.81 +/- 0.19 (p < 0.001), enalapril: 0.95 +/- 0.24, (p < 0.001), captopril: 1.09 +/- 0.27 (p < 0.02). Post exercise proteinuria three days after discontinuing the treatment was (blood pressure already back to baseline): in case of benazepril: 1.26 +/- 0.36 (p = n.s.), of enalapril: 1.17 +/- 0.46 (p = n.s.), and of captopril: 1.34 +/- 0.41 (p = n.s.). We conclude that the renin-angiotensin system plays a significant role in the pathogenesis of post exercise proteinuria; the antiproteinuric effect of ACE inhibition in exercise-induced proteinuria seems to be associated chiefly with the hemodynamic changes due to these drugs, whereas in chronic proteinuria the antiproteinuric and antihypertensive effects are, at least partially, dissociated.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Captopril; Chronic Disease; Diabetes Mellitus, Type 2; Enalapril; Exercise; Female; Glomerulonephritis; Humans; Male; Proteinuria

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

Rhein and angiotensin-converting enzyme inhibitor (ACEI) have been reported to prevent the progression of diabetic nephropathy (DN). We further explore the unknown ability to induce renal-protection of rhein and ACEI combined therapy in DN compared with the therapeutic effects of single treatment of them by using db/db mouse of type 2 diabetes model.. db/db and db/m mice, 8 weeks of age, were divided into five groups according to the following treatments: (A) db/m, given saline treatment; (B) db/db, given saline treatment; (C) db/db, given rhein treatment (150 mg/kg/day); (D) db/db, given benazepril treatment (10 mg/kg/day); (E) db/db, given rhein (150 mg/kg/day) with benazepril (10 mg/kg/day). Body weight, plasma glucose, plasma lipid and 24 h urinary albumin excretion levels were measured every 4 weeks. Morphometry of renal tissue and immunohistology of transforming growth factor-beta1 (TGF-beta) and fibronectin were determined for all groups at the end of the treatment.. It was found that after treatment urinary albumin excretion was reduced after 4 weeks treatment in group E and after 8 weeks treatment in groups C and D, when compared to group B (p<0.05). Plasma creatinine levels dropped significantly for group E, compared with the diabetic control group by the end of the treatment period. Furthermore, after the treatment body weight, plasma glucose, cholesterol, triglyceride and low density lipoprotein all decreased in groups C and E compared to group B (p<0.05). Histological morphometric analysis revealed that the whole glomerular area and extracellular matrix area was significantly reduced in groups C, D and E compared to group B, at 20 weeks of age, an effect most pronounced in group E. Using immunohistochemistry, the expression of fibronectin and TGF-beta1 in groups C, D and E was found to have decreased compared to group B, after 12 weeks treatment, again the effect being more pronounced in group E.. There appeared to be a similar renal protective effect of rhein compared with benazepril in diabetic nephropathy. A combined therapy may offer a more beneficial complementary effect on kidney injury in db/db mice, as reflected by urinary albumin excretion, renal function and histological changes. Our findings suggest that a therapeutic approach that combines rhein with ACEI provides a more effective therapy for DN than does either agent alone.

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Animals; Anthraquinones; Benzazepines; Blood Glucose; Cholesterol; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug Therapy, Combination; Enzyme Inhibitors; Fibronectins; Fluorescent Antibody Technique, Direct; Immunohistochemistry; Mice; Mice, Inbred C57BL; Random Allocation; Transforming Growth Factor beta; Triglycerides

The accumulation of advanced glycation end products (AGE) is a key factor in diabetic nephropathy (DN). Pyridoxamine inhibits AGE formation and protects against type I DN. Herein we tested: (1) whether C57BL6 db/db mice as a model of established type II DN resembled patients treated with drugs which inhibit angiotensin II action; (2) whether pyridoxamine was effective as a single therapy; and (3) whether pyridoxamine would add to the benefit of angiotensin-converting enzyme inhibition (ACEi) by enalapril. In first set of experiments mice were treated with ACEi (benazepril) and an angiotensin II receptor blocker (valsartan) combination for 16 weeks after the onset of diabetes. In second group, mice with established DN were treated with pyridoxamine for 8 weeks. In a third set, mice with established DN were treated with pyridoxamine and enalapril combination for 16 weeks. Benazepril and valsartan combination partially prevented the development and progression of DN. Pyridoxamine treatment, as single therapy, decreased the progression of albuminuria and glomerular lesions. The combination of pyridoxamine with enalapril reduced both mortality and the progression of DN. In conclusion, (1) C57 BL6 db/db mice are a model of progressive type II DN; (2) The combination of pyridoxamine with enalapril decreased progression of type 2 DN and overall mortality. Thus, pyridoxamine could be a valuable adjunct to the current treatment of established type II DN.

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Benzazepines; Collagen Type IV; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Drug Therapy, Combination; Enalapril; Female; Glycation End Products, Advanced; Mice; Mice, Inbred C57BL; Mice, Obese; Pyridoxamine; Tetrazoles; Valine; Valsartan; Vitamin B Complex

To study the effect of the Compound of traditional Chinese drugs and Benazepril on gene expression of renal endothelin and its receptor of experimental diabetic nephropathy(DN). To discove the mechanism of the compound of traditional Chinese drugs in treating DN.. Streptozotocin DN model was built and influenced with the compound of traditional Chinese drugs and Benazepril. The changes of Upro, Glu, HbA1C and (PT-PCR) mRNA expression levels of ET-1, ETA-R of the renal cortex were tested, and thus the histopathological character of the kidney was analysed.. The compound of traditional Chinese drugs and Benazepril have significant difference from normal saline in the improvement of Upro, Glu, HbA1C. The compound of traditional Chinese drugs have significant difference from Benazepril in the improvement of Glu, HbA1C. The mRNA expression level of ET-1, ETA-R of the renal cortex of DN model was raised. After influenced by the compound of traditional Chinese drugs and Benazepril, the over-expression level de-creased (still higher than normal control ones). The compound of traditional Chinese drugs were more effective than Benazepril to inhibit the proliferation of the stalk region and the third cells.. ET takes part in the process of diabetic glo-Merulosclerosis. Both the compound of traditional Chinese drugs and Benazepril can influence the expression quantity from the level of gene transcription of ET and its receptor. The compound of traditional Chinese drugs can not only reduce urinary albumin of DN, but also improve blood glucose, glycosylated hemoglubin. And it can inhibit nonenzymatic glucosylation of protein as well as the proliferation of the stalk region and the third cells.

Topics: Animals; Benzazepines; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug Combinations; Drugs, Chinese Herbal; Endothelin-1; Gene Expression; Kidney Cortex; Plants, Medicinal; Random Allocation; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; RNA, Messenger

ACE polymorphism, especially genotype DD or D allele, may be involved in the progression of diabetic nephropathy. It may also have different effects on the reduction of proteinuria by ACE inhibitors in patients with proteinuria. We investigated the relationship between ACE gene polymorphism and antiproteinuric effect of ACE inhibitors (Benazepril 10 mg/day or Perindopril 4 mg/day) in 83 NIDDM patients with overt proteinuria (urinary protein excretion over 500 mg/day).. We recruited NIDDM patients with overt proteinuria from our renal clinic. Before entry, previously used ACE inhibitors were withdrawn for at least 2 weeks and baseline proteinuria and albuminuria were measured. Patients were classified into three groups in accordance with ACE genotypes (17 DD; 33 ID; 33 II) and prospectively followed up for 3 months. Various clinical parameters including age, DM duration, body mass index (BMI), 24-h urine sodium, protein and albumin, BUN, serum creatinine, creatinine clearance (Ccr), mean arterial pressure (MAP), and HbA(1c) were measured in the pre- and post-treatment periods. ACE genotypes were determined by polymerase chain reaction.. There were no significant differences in the clinical parameters such as age, DM duration, BMI, BUN, serum creatinine, Ccr, MAP, HbA(1c), and daily urinary excretion of sodium, protein and albumin among three groups (P>0.05). After the 3-month treatment period using ACE inhibitors, there were no significant differences in the reduction of MAP and Ccr among the three groups (P>0.05). However, the percentage reductions in urinary excretion of protein and albumin for DD genotype were significantly higher than in ID and II genotypes (50.9+/-19.2% vs 19.2+/-16.0%, 20.2+/-20.4%; 52.6+/-23.6% vs. 13.5+/-51.8%, 24.8+/-23.9%, P<0.05). There were no statistically significant correlations between the levels of baseline proteinuria and albuminuria and the magnitudes of the reduction of proteinuria and albuminuria under ACE inhibition (P>0.05).. Our results suggest that the ACE gene polymorphism might have a role in determining the responsiveness to the antiproteinuric effect of ACE inhibition in proteinuric NIDDM patients.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Diabetes Mellitus, Type 2; Drug Resistance; Genotype; Humans; Middle Aged; Peptidyl-Dipeptidase A; Perindopril; Polymorphism, Genetic; Proteinuria