benazepril and Coronary-Disease

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

To determine the anti-ischaemic effects of a new angiotensin converting enzyme inhibitor, benazepril, compared with nifedipine, alone and in combination, in chronic stable angina caused by coronary artery disease.. Placebo controlled, double blind, latin square design.. Regional cardiology service for a mixed urban and rural population.. 40 patients with stable exertional angina producing at least 1 mm ST segment depression on exercise test with the Bruce protocol. 34 patients completed all four phases of the trial.. Each patient was treated with placebo, benazepril (10 mg twice daily), nifedipine retard (20 mg twice daily), and a combination of benazepril and nifedipine in the same doses, in random order for periods of two weeks.. Total duration of exercise was not increased by any treatment. Exercise time to the development of 1 mm ST segment depression was not significantly changed with benazepril alone or in combination with nifedipine but was increased with nifedipine from 4.18 (1.8) min to 4.99 (1.6) min (95% confidence interval (95% CI) 0.28 to 1.34; p < 0.05). There was a significant relation between increase in duration of exercise and resting renin concentration (r = 0.498; p < 0.01). Myocardial ischaemia during daily activity, as assessed by ambulatory electrocardiographic monitoring, was reduced by benazepril and by the benazepril and nifedipine combination. This was significant for total ischaemic burden (451(628) min v 231(408) min; 95% CI -398 to -41 min; p < 0.05) and maximal depth of ST segment depression (-2.47(1.2) mm v -2.16 mm; 95% CI 0.04 to 0.57; p < 0.05) for the combination and for maximal ST segment depth for benazepril monotherapy (-2.47 (1.2) mm v -1.96(1.2) mm; 95% CI 0.18 to 0.91; p < 0.05). Benazepril significantly altered the circadian rhythm of cardiac ischaemia, abolishing the peak ischaemic periods at 0700 to 1200 and 1700 to 2300 (p < 0.05).. Benazepril, an angiotensin converting enzyme inhibitor, had a modest anti-ischaemic effect in effort angina, but this effect was not as pronounced as with nifedipine. The anti-ischaemic action was more noticeable in asymptomatic ischaemia during daily activity, whereas nifedipine had little effect on this aspect of myocardial ischaemia. The combination of benazepril and nifedipine reduced ischaemia of daily activity.

Topics: Adult; Aged; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Chronic Disease; Coronary Disease; Double-Blind Method; Drug Therapy, Combination; Electrocardiography, Ambulatory; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Nifedipine

The anti-ischaemic properties of benazepril, a non-sulfhydryl inhibitor of angiotensin-converting enzyme, were assessed in 20 patients with chronic stable angina pectoris, by repeated exercise tests and repeated 72-h ambulatory electrocardiographic monitoring. The study was a double-blind, placebo-controlled cross-over; 11 patients received benazepril 10 mg b.i.d. and nine received 20 mg b.i.d. All patients had a positive treadmill stress test and at least three ischaemic episodes during 24 h of ambulatory electrocardiographic monitoring. Benazepril at a dose of 10 mg b.i.d. did not improve the exercise duration, the time taken to reach 1 mm ST depression. Similar findings were observed during treatment with 20 mg b.i.d. Benazepril at a dose of 10 mg b.i.d. was ineffective in improving ischaemic parameters during daily activities. However, among the nine patients who received 20 mg b.i.d. the number of ischaemic episodes was reduced from 142 to 103, and the total duration of ischaemic was reduced from 1099 to 531 min. The number of weekly anginal attacks was reduced from 58 to 33, and the weekly sublingual nitroglycerin tablets consumption was reduced from 31 to 14. When the two doses (10 mg and 20 mg) were combined (N = 20), the number of ischaemic episodes was reduced from 314 to 260 (P = 0.074), and the duration of ischaemic was reduced from 3453 to 2514 min (P = 0.072).

Topics: Aged; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Coronary Disease; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Nitroglycerin

The antiischemic efficacy of the converting enzyme inhibitor (CEI) benazepril was investigated in a randomized, placebo-controlled double-blind study with intraindividual crossover in 11 normotensive patients with angiographically proven coronary artery disease. Bicycle ergometry and 24-h ambulatory ECG were performed before and after 2-week treatment with placebo and benazepril, respectively. Plasma concentrations of atrial natriuretic peptide (ANP) and plasma renin activity (PRA) were measured before each exercise test. Maximal exercise-induced ST-segment depression was not significantly influenced by benazepril therapy (placebo 2.09 +/- 1.22 mm, benazepril 1.91 +/- 1.00 mm). Systolic blood pressure/heart rate (SBP/HR) product at maximum workload remained almost constant with 253 +/- 43 with placebo and 253 +/- 39 with benazepril treatment. The number of anginal attacks and ischemic episodes detected by ambulatory ECG were not significantly reduced. PRA increased significantly from 2.18 +/- 3.76 to 9.62 +/- 8.49 ng/ml/h after benazepril (p less than 0.005), whereas plasma concentrations of ANP remained unchanged (28.04 +/- 12.39 vs. 26.73 +/- 11.09 pg/ml). Therefore, measurement of ST-segment depression with exercise in 11 normotensive patients with coronary artery disease produced no evidence of an antiischemic action for the CEI benazepril 10 mg twice daily (b.i.d.) for 2 weeks, but an improvement was observed in six patients.

Topics: Adult; Aged; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Coronary Disease; Double-Blind Method; Electrocardiography; Exercise Test; Humans; Male; Middle Aged

To investigate the potential anti-ischaemic effects of benazepril (10 mg bid) in comparison to placebo, this new ACE-inhibitor was given to 11 patients with chronic stable angina, reproducible exercise-induced ST-segment depression and angiographically verified coronary artery disease. Blood pressure at rest, plasma renin activity, and plasma concentration of atrial natriuretic peptide were measured after treatment periods of two weeks. Bicycle exercise tests at the same time should evaluate ST-segment depression at comparable maximal workload, work capacity, blood pressure, and heart rate at exercise. In comparison to placebo, benazepril reduced arterial blood pressure significantly from 140 +/- 14/90 +/- 11 mm Hg to 125 +/- 16/84 +/- 10 mm Hg (p less than 0.05) and increased plasma renin activity from 2.19 +/- 3.76 ng/ml/h to 9.62 +/- 8.49 ng/ml/h (p less than 0.005). In contrast, ST-segment depression decreased only slightly and not significantly from 2.09 +/- 1.22 mm to 1.91 +/- 1.00 mm. Benazepril had neither an effect on the frequency of episodes of angina pectoris nor did it reduce the amount of GTN-consumption. Also, work capacity and plasma concentration of atrial natriuretic peptide were not changed in comparison to placebo. Although the significant reduction of blood pressure and the highly significant increase of plasma renin activity demonstrate the specific action of benazepril, a significant anti-ischaemic effect could not be established.

Topics: Adult; Aged; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Coronary Disease; Double-Blind Method; Electrocardiography; Exercise Test; Humans; Male; Middle Aged

The efficacy of benazepril, metoprolol OROS and their combination was evaluated in 29 patients (42 to 74 years of age) with chronic stable angina and documented coronary artery disease in a placebo-controlled, double-blind, crossover trial using serial quantitated exercise testing and ambulatory electrocardiographic (ECG) monitoring. The mean (+/- SEM) exercise time was 8.5 +/- 0.7 min with placebo, 8.3 +/- 0.6 min (95% confidence interval [CI]-1.06 to 0.54) with benazepril, 9.4 +/- 0.5 min (95% CI -0.32 to 2.14) with metoprolol OROS and 9.6 +/- 0.5 min (95% CI -0.25 to 2.47) with the combination of benazepril and metoprolol OROS. The mean exercise time to the development of 1 mm ST segment depression was prolonged from 6.0 +/- 0.6 min with placebo to 6.3 +/- 0.6 min (95% CI -0.93 to 1.45) with benazepril, 7.9 +/- 0.5 min (95% CI 0.83 to 3.0) with metoprolol OROS and 8.1 +/- 0.6 min (95% CI 0.88 to 3.29) with the combination of benazepril and metoprolol OROS. Benazepril did not alter the rest or maximal heart rate, whereas metoprolol OROS alone and in combination significantly lowered the heart rate at rest and during maximal exercise. Systolic blood pressure at rest was nonsignificantly reduced, whereas diastolic blood pressure was lowered significantly by all treatments in comparison with placebo. At maximal exercise, only metoprolol OROS, whether given alone or in combination with benazepril, was able to blunt significantly systolic blood pressure and rate-pressure product.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Coronary Disease; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Electrocardiography, Ambulatory; Exercise Test; Female; Humans; Male; Metoprolol; Middle Aged

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

We investigated the role of vascular angiotensin-converting enzyme (ACE) activity, cell proliferation, and the effect of different doses of benazepril on intimal hyperplasia after angioplasty in rabbits. Angioplasty was performed in all left iliac arteries in 28 rabbits. Benazepril was administrated to treatment groups in low (1 mg/kg/day) and high (10 mg/kg/day) doses. Two weeks after angioplasty, vascular ACE activity of the angioplasty subgroup was significantly higher than that of the nonangioplasty subgroup (from 0.44 to 1.19 nmol His-Leu/mg/min; p < 0.01). Strong correlation was demonstrated between vascular ACE activity and intimal area (r = 0.708; p < 0.01). Suppression of vascular ACE activity (59% decrease) and inhibition of intimal hyperplasia (43% decrease) was observed in the high-dose subgroup compared with the angioplasty subgroup without drug intervention (p < 0.01). But in the low-dose subgroup, the level of vascular ACE activity decreased moderately (24.4%; p < 0.05), and the intimal area did not alter significantly. Both the low and high dosage of benazepril resulted in a significant decrease in blood pressure (31 and 44 mm Hg, respectively). Striking correlation was displayed between proliferating-cell nuclear antigen (PCNA)-positive cell percentage and intimal area (r = 0.716; p < 0.01). These results indicated that with excessive expression of vascular ACE, intimal cellular proliferation may play a potential role in restenosis after angioplasty. Benazepril could inhibit intimal hyperplasia by suppressing vascular-tissue ACE.

Topics: Analysis of Variance; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Biomarkers; Blood Pressure; Cell Division; Coronary Disease; Coronary Vessels; Disease Models, Animal; Hyperplasia; Male; Peptidyl-Dipeptidase A; Proliferating Cell Nuclear Antigen; Rabbits; Tunica Intima

To examine the hemodynamic effects of benazepril, an angiotensin converting enzyme inhibitor, in left ventricular failure, its active metabolite benazeprilat was administered during acute ischemic left ventricular failure in anesthetized open chest dog induced by repeated injections of plastic microspheres into the left coronary artery. The coronary embolization with microspheres resulted in a moderate and stable left ventricular pump failure characterized by increased left ventricular end-diastolic pressure (LVEDP) and decreased cardiac output (CO). Benazeprilat (30 micrograms/kg) administered intravenously after a stabilization period lowered LVEDP and maintained CO. The total peripheral resistance was reduced with benazeprilat. The oxygen consumption and the coronary blood flow were reduced with benazeprilat because of a decrease in wall tension and afterload. These results suggest that benazeprilat (benazepril) has beneficial effects for the treatment of acute left ventricular failure.

Topics: Acute Disease; Animals; Benzazepines; Coronary Disease; Dogs; Heart Failure; Hemodynamics; Microspheres; Ventricular Function, Left

Topics: Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Coronary Disease; Delayed-Action Preparations; Humans; Metoprolol