benazepril and Myocardial-Infarction

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

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

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

Sixty patients, mean age 82 +/- 8 years, with congestive heart failure, prior myocardial infarction, normal left ventricular ejection fraction, and > or = 30 ventricular premature complexes per hour detected by 24-hour ambulatory electrocardiograms, and who were treated with diuretics, were randomized to treatment with benazepril 20 to 40 mg/day (30 patients) or to no benazepril (30 patients). At a median of 6 months after treatment, follow-up 24-hour ambulatory electrocardiograms showed that compared with no benazepril, benazepril caused no significant reduction in the number of ventricular premature complexes per hour or in the number of runs of ventricular tachycardia per 24 hours.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Electrocardiography, Ambulatory; Female; Fourier Analysis; Heart Failure; Hemodynamics; Humans; Male; Myocardial Infarction; Prospective Studies; Signal Processing, Computer-Assisted; Stroke Volume; Tachycardia, Ventricular; Ventricular Function, Left

We studied 14 patients who had exercise-induced ventricular arrhythmias after a previous Q-wave myocardial infarction. All had symptomatic mild heart failure in New York Heart Association class II and a maximal oxygen consumption between 16 and 20 ml/kg/min. They were treated with the angiotensin converting enzyme inhibitor benazepril (20 mg) and hydrochlorothiazide (50 mg) for 3 months in a double-blind randomized cross-over study. Benazepril improved the maximal oxygen uptake by 15% and exercise time by 18%. Hydrochlorothiazide slightly increased exercise time (5%) and the respiratory exchange ratio but not oxygen consumption. The arrhythmias were nonsustained and reproducible in two baseline recordings. Compared with baseline, benazepril reduced the mean number (3.5 +/- 2.5) (+/- SD) of episodes of ventricular tachycardia by 66%, and total (47.4 +/- 40.9) and paired (5.2 +/- 4.5) premature ventricular contractions by 61% and 62%, respectively. Hydrochlorothiazide did not reduce the number of arrhythmias. Thus an improved cardiac function induced by benazepril is associated with a reduction in exercise-induced ventricular arrhythmias in patients with symptomatic mild heart failure after infarction.

Topics: Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Cardiac Complexes, Premature; Double-Blind Method; Electrocardiography, Ambulatory; Exercise; Exercise Test; Heart Failure; Humans; Hydrochlorothiazide; Myocardial Infarction; Tachycardia, Ventricular

LCZ696, an angiotensin receptor-neprilysin inhibitor (ARNi), is reported to play a cardioprotective role after acute myocardial infarction (AMI). Angiotensin-converting enzyme inhibitors(ACEIs) have similar roles. However, it is unclear whether the combination of the two drugs has a better protective effect. The purpose of this study was to investigate the effect of this combination therapy after AMI.. Male C57BL/6 J mice subjected to ligation of left anterior descending artery were treated for 4 weeks with LCZ696, ACEI(benazepril), or both(combination therapy) after induction of MI. Cardiac function, hemodynamics, and inflammatory factors were evaluated at 1 st day, 14th day, and 28th day. Heart weight and myocardial fibrosis were measured at the end of the experiment.. Blood pressure was lower in all treatment groups than in the control group. The combination therapy group had the strongest antihypertensive effect. Compared with LCZ696 or benazepril, treatment with combination therapy increased ejection fraction, fractional shortening, and cardiac output and decreased N-terminal pro-B-type natriuretic peptide(NT-proBNP). The ratios of heart weight to body weight in all treatment groups were less than that in the control group. Compared with the control and LCZ696 group, the fibrotic area in the combination therapy group was suppressed and had a lower level of TGF-β1 in the left ventricle. The plasma concentration of bradykinin and renin in the combination therapy group were highest among groups at 14th and 28th day.. LCZ696 in combination with benazepril showed better positive effects in modulating heart failure and myocardial fibrosis after acute AMI in mice and affect some inflammatory markers.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Biphenyl Compounds; Disease Models, Animal; Drug Combinations; Drug Therapy, Combination; Fibrosis; Heart Failure; Hemodynamics; Inflammation Mediators; Male; Mice, Inbred C57BL; Myocardial Contraction; Myocardial Infarction; Myocardium; Neprilysin; Protease Inhibitors; Renin; Tetrazoles; Transforming Growth Factor beta1; Valsartan; Ventricular Function, Left

The present study evaluated the effects of benazepril, an angiotensin-converting enzyme inhibitor on haemodynamic, biochemical, and immunohistochemical (Bax and Bcl-2 protein) indices in ischaemia and reperfusion (IR) injury.. Male Wistar albino rats were divided into three groups and were orally administered saline once daily (IR-sham and IR-control) or benazepril (30 mg/kg/day; IR-benazepril) for 14 days. On the 15(th) day, in the IR-control and IR-benazepril groups, rats were subjected to left anterior descending coronary artery occlusion for 45 minutes followed by a one-hour reperfusion. Haemodynamic parameters were recorded and rats were sacrificed; hearts were isolated for biochemical estimation and immunohistochemistry.. In the IR-control group, significant ventricular dysfunctions (p<0.05 vs. IR-sham group) were observed along with enhanced expression of pro-apoptotic protein Bax. A decline in lactate dehydrogenase activity and increased content of thiobarbituric acid reactive substances, a marker of lipid peroxidation, were observed. Benazepril pretreatment significantly improved mean arterial pressure (p<0.01), reduced left ventricular end-diastolic pressure (p<0.05), and improved both inotropic and lusitropic function of the heart (+LVdP/dt and - LVdP/dt) (p<0.05; p<0.01) as compared to IR-control. Furthermore, benazepril treatment significantly decreased the level of thiobarbituric acid reactive substances and restored the activity of lactate dehydrogenase towards normal value (p<0.05 vs. IR-control).. This study demonstrates that benazepril upregulated Bcl-2 protein and decreased Bax protein expression, thus exhibiting anti-apoptotic effects. These beneficial effects of benazepril will have an important implication in the therapeutic use of benazepril in ischaemic heart disease.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; bcl-2-Associated X Protein; Benzazepines; Gene Expression; Lipid Peroxidation; Male; Malondialdehyde; Myocardial Infarction; Myocardial Reperfusion Injury; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar

The aim of this study was to compare the cardioprotective effects of salvianolic acid B (Sal B) and the angiotension-converting enzyme inhibitor, benazepril, in rats with chronic myocardial infarction (MI) that resulted from a coronary artery ligation for 4 weeks. The rats were divided into four groups: those undergoing a sham operation; a MI group; a MI+SalB group (100 mg/kg by a gavage, once a day for 4 weeks); a MI+benazepril group (10 mg/kg by a gavage, once a day for 4 weeks). The following parameters were measured: echocardiographic, hemodynamic and hemorheological changes, angiogenesis, infarct size and cardiac remodeling and the messenger ribonucleic acid (mRNA) of vascular endothelium growth factor (VEGF). Rats treated with SalB or benazepril manifested the following: (1) marked improvements in echocardiographic, hemodynamic and hemorheological parameters; (2) significant reduction of infarct size; (3) significantly attenuated heart, kidney and lung hypertrophies, left ventricular (LV) dilatation and fibrosis. The unique effects of SalB were angiogenesis and augmented VEGF expression in the border and remote noninfarcted left ventricular area. These results suggest that both SalB and benazepril exerted beneficial cardioprotective effects in our experimental system, but that the modality of Sal B was different from that of benazepril. The additional beneficial effects of Sal B relative to benazpril, augmenting VEGF expression and promoting angiogenesis, may result in improved myocardial microcirculation.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antioxidants; Benzazepines; Benzofurans; Blood Viscosity; Cardiomegaly; Chronic Disease; Collagen; Electrocardiography; Hemodynamics; Immunohistochemistry; Male; Myocardial Infarction; Myocardium; Neovascularization, Pathologic; Protective Agents; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Vascular Endothelial Growth Factor A; Ventricular Remodeling

A 10-year-old cat with the paresis of hind limbs was initially diagnosed as a hypertrophic cardiomyopathy followed by acute thromboembolism of caudal abdominal aorta from the findings of the medical examinations. However, this case was proved to be an chronic myocardial infarction due to arteriosclerosis of coronary arteries by the pathologic diagnosis. In the left ventricular, the hypertrophy and the narrowing were slight, and a coagulative infarction was seen obviously. The intramural coronary arteriosclerosis showed thickening of the wall due to medial hyperplasia by fibrosis, and arterial stenosis. Myocardial infarction and arteriosclerosis are scarcely any reports of these lesions in cats. This case is valuable for an extremely rare case of myocardial infarction in the cat.

Topics: Animals; Aorta, Abdominal; Benzazepines; Cat Diseases; Cats; Coronary Artery Disease; Diltiazem; Dipyridamole; Echocardiography, Doppler; Electrocardiography; Fatal Outcome; Myocardial Infarction; Propranolol; Thromboembolism

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

To explore the changes of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and angiogenesis, and the effects of bFGF, angiotensin converting enzyme inhibiter(ACEI) benazepril on the angiogenesis in acute myocardial infarction (AMI) model of rabbits, and to provide a probable evidence for the treatment of AMI.. AMI model was established by ligating anterior descending branch of coronary artery of Japan-Sino hybridization white rabbits. The postoperative rabbits were randomly divided into 6 groups and each group was treated with different drugs. Groups 1 and 2 were treated with normal saline (NS) for 28 and 14 days (d), group 3 and 4 with bFGF for 28 and 14 d, groups 5 with benazepril for 14 d, and group 6 with benazepril and bFGF for 14 d respectively. The rabbits were killed on the 14th or 28th d and their hearts were excised, sectioned and stained with HE, Masson trichrome to observe VEGF, bFGF and CD(34) under a microscope, which were quantified with a computer-assisted morphometry.. Compared with group 1, the granulation tissue of infarction zone (IZ) in group 2 freshened up, and the capillary density (CD) in IZ was increased (P = 0.002). The CD in the IZ as well as VEGF and bFGF in groups 3 and 4 were increased respectively (P = 0.011-0.037). In group 5 the changes of VEGF and bFGF were not found in the IZ and the border zone (BZ) while CD was significantly increased (35.4% and 25.6%, P = 0.036 and 0.037). Compared with group 2, the CD in the IZ and BZ of group 6 was significantly increased (63.4% and 44.3% P = 0.007 and 0.007), meanwhile VEGF and bFGF were increased. Compared with group 5, only VEGF was increased.. Intravenous bFGF may increase VEGF and bFGF significantly, thus promoting the angiogenesis in the IZ and BZ in cardiac infarction as VEGF and bFGF are the potent angiogenic growth factors. Benazepril may promote angiogenesis in the IZ and BZ in cardiac infarction, but its mechanism is irrelative to the expression of VEGF and bFGF. The combination of benazepril and bFGF may promote, to some extent, the expression of VEGF and bFGF, but their effect on angiogenesis has not been found.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Coronary Circulation; Coronary Vessels; Disease Models, Animal; Fibroblast Growth Factor 2; Myocardial Infarction; Neovascularization, Physiologic; Rabbits; Time Factors; Vascular Endothelial Growth Factor A

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Female; Humans; Male; Middle Aged; Myocardial Infarction; Treatment Outcome