benazepril and Angina-Pectoris

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

We have previously shown that transdermal nitroglycerin may induce an increase in the activity of the adrenergic and the renin-angiotensin-aldosterone systems (SRAA) in patients with chronic stable angina pectoris (SA); when the activation of these systems is more pronounced, the antianginal effect of this drug seems to be reduced. The aim of this study was to evaluate the antianginal efficacy of transdermal nitroglycerin administration (TTS-NG 10 mg.24 h-1) in combination with an ACE inhibitor without sulphydryl groups (BNZ, benazepril 10 mg b.i.d.) in respect to placebo, or to TTS-NG or BNZ administered as monotherapy. Twenty-four patients (21M, 3F) were admitted to this multicentre, randomized, double-blind, latin square, placebo-controlled study. Patients received all the treatments (placebo, TTS-NG, BNZ and BNZ + TTS-NG) each for one week; at the end of each week patients performed two exercise tests 2 and 22 h post-dosing. Two hours post-dosing, exercise duration at 1 mm ST depression was significantly increased in respect to placebo during TTS-NG (P < 0.05) and TTS-NG + BNZ (P < 0.05) treatments. Two hours post-dosing, exercise duration at peak exercise was also increased in respect to placebo during TTS-NG (P < 0.05) and TTS-NG + BNZ (P < 0.05); 22 h post-dosing the increase in exercise duration was significant only during TTS-NG + BNZ treatment (P < 0.05) in respect to placebo, but not during TTS-NG given alone. Rate-pressure product at 1 mm ST depression was significantly increased 2 h post-dosing during TTS-NG treatment (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Cutaneous; Aged; Aldosterone; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Epinephrine; Exercise Tolerance; Female; Humans; Male; Middle Aged; Nitroglycerin; Norepinephrine; Renin

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

The aim of this study was to evaluate the anti-ischemic efficacy of 2 different doses of benazepril (B), a new ACE-inhibitor, 10 and 20 mg, given per os. Fifteen male patients gave informed, written consent; they were aged 40-67 years, with stable effort angina pectoris and were randomly given, in double-blind condition, a tablet containing B 10 mg, B 20 mg or placebo (PL), once a day, according to a 3 x 3 latin square design. Bicycle exercise tests were performed on the same day, 2 and 10 hours after the last drug intake. B 10 mg and B 20 mg, in patients with stable effort angina, compared to placebo, increased ischemic threshold and decreased ischemic ST depression at maximal work, after 2 hours but not after 10 hours. In conclusion B 10 mg and B 20 mg showed anti-ischemic activity 2 hours after drug intake.

Topics: Adult; Aged; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; 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

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