enalapril and Coronary-Disease

Type 2 diabetes is reaching epidemic proportions throughout the world, which has major health implications as such patients have considerably increased risk of coronary heart disease (CHD). The renin-angiotensin-aldosterone system (RAAS) is involved in a wide range of adverse effects that contribute to the pathogenesis of CHD in diabetic patients, including vascular haemodynamic regulation, oxidative stress and hypertrophy of vascular cells. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are widely used in clinical practice. In diabetic patients ACE inhibitors and ARBs both effectively lower blood pressure, particularly in combination with low-dose thiazide diuretics, and may be considered first line therapies in the treatment of diabetic hypertension. Additionally they have important renoprotective actions independent of their blood pressure-lowering action, which is of particular benefit in diabetic patients, who are at increased risk of developing nephropathy. ARBs are generally well tolerated, but ACE inhibitor therapy is associated with some side effects such as cough and both may result in hyperkalaemia. Blockade of the RAAS with these agents appears to play an important role not only in protecting from renal disease, but it may also help to reduce morbidity and mortality from certain vascular diseases in diabetic patients.

Topics: Angiotensin-Converting Enzyme Inhibitors; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Enalapril; Heart Failure; Humans; Randomized Controlled Trials as Topic; Renin-Angiotensin System

Left ventricular hypertrophy (LVH) is a strong, independent predictor of cardiovascular events and all-cause mortality. Patients with LVH are at increased risk for stroke, coronary heart disease, congestive heart failure, and sudden cardiac death. Hypertension is a major influence on the development of LVH. The prognostic power of LVH is likely multifactorial. LVH represents both a manifestation of the effects of hypertension and other cardiac risk factors over time as well as an intrinsic condition causing pathologic changes in cardiac structure and function. Angiotensin II plays a central role in the development of LVH. Several antihypertensive treatments, especially angiotensin II receptor blockers, can reverse LVH and improve cardiovascular outcomes independent of blood pressure reduction. Further studies are required to determine if these agents should become first-line therapy for all patients with hypertension and LVH.

Topics: Adrenergic Antagonists; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Benzoates; Carbazoles; Carvedilol; Chi-Square Distribution; Cohort Studies; Coronary Disease; Death, Sudden, Cardiac; Diuretics; Drug Therapy, Combination; Echocardiography; Electroencephalography; Enalapril; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Indapamide; Logistic Models; Losartan; Male; Multivariate Analysis; Prognosis; Propanolamines; Prospective Studies; Randomized Controlled Trials as Topic; Risk; Risk Assessment; Risk Factors; Sex Factors; Stroke; Survival Analysis; Telmisartan

Many clinical trials have been conducted to prevent cardiovascular complications and reduce mortality in hypertensive patients. Undoubted, but limited effects of beta-blocker and diuretic antihypertensive drugs had been established. Although angiotensin-converting enzyme inhibitor and angiotensin II receptor antagonist lowered the incidence of events and mortality less than classical antihypertensive drugs, recent studies revealed that prompt and enough lowering the blood pressure is more important than choosing the types of drugs.

Topics: Adrenergic beta-Antagonists; Aged; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Coronary Disease; Diuretics; Double-Blind Method; Drug Therapy, Combination; Enalapril; Humans; Hypertension; Losartan; Randomized Controlled Trials as Topic; Treatment Outcome

The results of the major clinical outcome trials related to the potential antiatherosclerotic effects of the angiotensin convertase (ACE) inhibitors are reviewed after the recently published EUROPA trial results. In the postinfarction clinical situation mortality reduction was revealed in the ISIS-4 (captopril), GISSI-3 (lisinopril), AIRE (ramipril), TRACE (trandolapril), CONSENSUS (enalapril), SAVE (captopril) and in the SOLVD (enalapril) trials. In the HOPE trial performed in a high risk population the preventive antiatherosclerotic, endothel-preserving effects of ramipril resulted in a significant mortality and morbidity reduction. In the EUROPA trial a lower risk population--symptomfree coronary patients--were treated by perindopril, and it was proven also in this cohort, that the long term ACE inhibitor treatment decreased the combined endpoint of cardiovascular mortality, myocardial infarction and resuscitated sudden death. Based on the above data it can be advised, that all coronary patients regardless of left ventricular function and symptoms should receive long term ACE inhibitor treatment besides the other established preventive medications (platelet aggregation inhibitors + statins + beta receptor blockers).

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Clinical Trials as Topic; Coronary Disease; Death, Sudden, Cardiac; Enalapril; Humans; Indoles; Lisinopril; Myocardial Infarction; Perindopril; Ramipril; Treatment Outcome

Asymptomatic left ventricular dysfunction should be treated as an early stage on the continuum that is chronic heart failure. The author presents the clinical trial data on which current management with angiotensin-converting enzyme inhibitors and beta-blockers is based. Issues surrounding screening are also discussed.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Coronary Disease; Drug Therapy, Combination; Echocardiography; Enalapril; Female; Heart Failure; Humans; Hypertension; Indoles; Male; Middle Aged; Myocardial Infarction; Norepinephrine; Ramipril; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

The failure of encainide and flecainide to reduce mortality after infarction in the Cardiac Arrhythmia Suppression Trial and the failure of low-dose amiodarone to prevent sudden cardiac death in patients with a low left ventricular ejection fraction has shifted attention to other strategies, such as beta-adrenergic blocking agents, to prevent sudden cardiac death. Evidence suggesting that beta-adrenergic blocking agents might be useful, especially in patients with low left ventricular ejection fraction, is accumulating. Previous data from studies using beta-adrenergic blocking agents and the mechanisms by which beta-adrenergic blocking agents might be of value in preventing sudden cardiac death are reviewed. These considerations and the availability of new investigational beta-adrenergic blocking agents with vasodilator properties provide a new opportunity to test the hypothesis that beta-adrenergic blocking agents are useful in preventing sudden cardiac death, especially in patients with a low left ventricular ejection fraction.

Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Cardiac Output, Low; Cardiomyopathy, Dilated; Catecholamines; Clinical Trials as Topic; Coronary Disease; Death, Sudden, Cardiac; Diuretics; Enalapril; Heart Ventricles; Humans; Magnesium; Myocardial Infarction

We examined the influence of angiotensin converting enzyme inhibitors (ACE inhibitors) on mortality in patients with heart failure of both ischaemic or non-ischaemic origin. Eleven, randomized, placebo-controlled trials of ACE inhibitors involving 1266 patients were selected. The follow-up period varied from 3 to 6 months. Four different ACE inhibitors were used in the 11 clinical trials. A total of 679 patients presented with an ischaemic heart failure and 587 with a non-ischaemic heart failure. Meta-analysis, performed for both subgroups, showed that mortality was significantly decreased in the ischaemic subgroup only (ischaemic group: odds ratio 0.45; 95% confidence interval 0.28 to 0.71; non-ischaemic subgroup: odds ratio 0.7; 95% confidence interval 0.4 to 1.5). Although the two odds ratio are not significantly different, further randomized, placebo-controlled trials with ACE inhibitors are required in order to determine more precisely the benefit/risk ratio in patients with non-ischaemic heart failure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Coronary Disease; Enalapril; Follow-Up Studies; Heart Failure; Humans; Indoles; Meta-Analysis as Topic; Perindopril; Survival Rate

Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Adult; Blood Pressure; Calcium Channel Blockers; Captopril; Combined Modality Therapy; Coronary Disease; Diuretics; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enalapril; Female; Humans; Hypertension; Hypokalemia; Male; Methods; Middle Aged; Reserpine; Risk

The inhibition of the renin-angiotensin system (RAS) has important effects on different parameters of left ventricular function. Chronic inhibition of the RAS avoids hypokalemia and potassium losses by increasing aldosterone release. This potassium-sparing effect is likely to prevent cardiac arrhythmia. Inhibition of the RAS reverses cardiac hypertrophy in renovascular and in spontaneously hypertensive rats (SHR), but not in DOCA salt hypertensive rats. Inhibition of the RAS also reverses the decrease in myocardial contractility, as demonstrated by the reversion of isoenzyme profile of cardiac myosin in renovascular hypertensive rats. In DOCA salt hypertensive rats, RAS inhibition has no effect on blood pressure or on cardiac contractility. Despite its peripheral vasodilatory property, inhibition of the RAS does not increase heart rate in relation to a direct negative chronotropic effect of angiotensin II inhibition and to the absence of activation of the baroreflex system. When RAS is activated, its inhibition has a coronary vasodilatory effect, but this coronary vasodilation is associated with a decrease in perfusion pressure and with an increase in intrinsic cardiac contractility. These concomitant effects lead us to conclude that inhibition of RAS probably has no important beneficial effect on the oxygen demand/oxygen supply ratio in the myocardium distal to the coronary artery stenosis.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiomegaly; Coronary Circulation; Coronary Disease; Dipeptides; Enalapril; Heart; Heart Rate; Humans; Myocardial Contraction; Oxygen Consumption; Potassium; Renin-Angiotensin System

Arterial hypertension is by definition a haemodynamic disorder. At least 3 different subsets of cardiovascular pathophysiological features can be identified in so-called essential hypertension: The young lean patient characterised by an elevated cardiac output and renal blood flow, elevated plasma renin activity and circulating catecholamine levels, as well as symptoms and signs of hyperadrenergic hypertension. The elderly patient characterised by a low cardiac output often with left ventricular hypertrophy, elevated total peripheral resistance, nephrosclerosis, and symptoms and signs of target organ disease. The obese patient (and to a lesser degree the black patient) characterised by expanded fluid volume state, elevated cardiac output, a normal to low total peripheral resistance, and symptoms and signs of volume overload. To initiate antihypertensive therapy, the drug of choice in the young patient is a beta-adrenergic receptor blocker; in the elderly it is a haemodynamic vasodilator (anti-adrenergic drug, slow channel calcium blocker, or converting enzyme (ACE) inhibitor), and in black or obese patients it remains a thiazide diuretic. Enalapril, a new ACE inhibitor is indicated as a first-step agent in the great majority of hypertensive patients in whom the elevated arterial pressure should be reduced by a decrease in total peripheral resistance, without compromising systemic or regional blood flow. In contrast to other antihypertensive agents, enalapril will lower preload and afterload to the left ventricle while improving systemic and regional flow in elderly patients with latent or manifest congestive heart failure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arrhythmias, Cardiac; Cardiomegaly; Coronary Disease; Enalapril; Heart; Hemodynamics; Humans; Hypertension; Obesity; Racial Groups

Patients (pts) with stable coronary artery disease (CAD) can benefit from a decrease in the blood pressure (BP), according to recent studies.. To evaluate the efficacy and tolerability of the fixed combination: amlodipine + enalapril, when compared to amlodipine in the normalization of the diastolic arterial pressure (DAP) (<85 mmHg), in pts with CAD and systemic arterial hypertension (SAH).. Double-blind and randomized study, with two groups of pts with DAP > or =90 and <110 mmHg and CAD. Patients with left ventricular ejection fraction (LVEF) < 40%, symptoms of heart failure or angina class III and IV, severe diseases and DAP > or =110 mmHg during the four-week wash-out with atenolol treatment alone, were excluded. After the wash-out, pts were randomly distributed for the use of the combination (A) or amlodipine (B) and were followed every four weeks up to 98 days. The initial doses (in mg) were, respectively: A- 2.5/10 and B- 2.5; the doses were increased when DAP > 85mmHg, at the visits. Statistical analysis was carried out with chi2, Fischer and analysis of variance, for p< 0.05.. Of the 110 selected pts, 72 (A= 32, B= 40) were randomized. The decreases in DAP and systolic arterial pressure (SAP) were significant (p< 0.01), but with no difference between the groups in mmHg: SAP, A (127.7 +/- 13.4) and B (125.3 +/- 12.6) (p= 0.45) and DAP, A (74.5 +/- 6.7 mmHg) and B (75.5 +/- 6.7 mmHg) (p= 0.32). Group A presented a lower incidence of lower-limb edema: (7.1% vs 30.6%, p=0.02) on the 98th day of follow-up.. The fixed combination of enalapril and amlodipine, as well as isolated amlodipine, was effective in the normalization of BP in pts with CAD and SAH stages I and II, adding blockage of the renin-angiotensin system.

Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Coronary Disease; Drug Therapy, Combination; Edema; Enalapril; Epidemiologic Methods; Female; Humans; Hypertension; Lower Extremity; Male; Middle Aged

To assess duration of a clinical response and tolerance of structum in patients with low back pain (LBP) and comorbid cardiovascular disease.. 25 patients with primary LBP and coronary heart disease (n = 13) and/or essential arterial hypertension (n = 18) were examined and treated for 6 months with structum.. To the end of the first treatment months structum significantly relieved pain intensity, spinal motility, increased exercise tolerance. Excellent and good response to structum were observed in 71% patients, no response was in 29%. Tolerance of the drug was good in 23 (92%) patients. The effect persisted for 3 months. CHD characteristics did not change while arterial pressure went down noticiably.. Structum is highly effective in the treatment of LBP. Its long-term intake had no effect on CHD.

Topics: Adult; Aged; Chondroitin Sulfates; Coronary Disease; Drug Therapy, Combination; Enalapril; Exercise Tolerance; Female; Humans; Hypertension; Low Back Pain; Male; Middle Aged; Syndrome; Treatment Outcome

The goal of this study was to investigate whether concomitant therapy with vasoactive medications alters the results of noninvasive assessment of endothelial function.. Ultrasound assessment of brachial artery flow-mediated dilation is emerging as a useful clinical tool. The current practice of withholding cardiac medications before ultrasound studies has unknown utility and would limit the clinical use of the methodology.. To determine whether a single dose of a vasoactive drug influences brachial reactivity, we examined flow-mediated dilation and nitroglycerin-mediated dilation in 73 healthy subjects (age 27 +/- 6 years). Studies were completed at baseline and 3 h after randomized treatment with a single oral dose of placebo, felodipine (5 mg), metoprolol (50 mg), or enalapril (10 mg). To determine if holding vasoactive therapy for 24 h before study yields different results than continuation of clinically prescribed medications, we examined vascular function in 72 patients (age 57 +/- 10 years) with coronary artery disease. Ultrasound studies were performed 24 h after the last dose and again 3 h after patients took their clinically prescribed medications.. In healthy subjects one dose of all three drugs lowered blood pressure, and metoprolol also lowered heart rate. However, there was no significant effect of treatment on brachial artery dilation. In patients with coronary artery disease on chronic treatment, taking prescribed medications reduced blood pressure and heart rate, but had no significant effect on brachial artery dilation.. Recent administration of commonly used nonnitrate vasoactive drugs has no significant effect on brachial reactivity. These findings suggest that current practice of withholding cardiac medications before testing endothelial function may not be necessary, making this methodology more practical for clinical use.

Topics: Adult; Analysis of Variance; Brachial Artery; Cardiovascular Agents; Coronary Disease; Double-Blind Method; Enalapril; Endothelium, Vascular; Felodipine; Female; Humans; Male; Metoprolol; Models, Cardiovascular; Reference Values; Reproducibility of Results; Vasodilation

ACE inhibitors may have a cardioprotective effect by enhancing bradykinin levels during cardiopulmonary bypass (CPB). However, ACE inhibition could lead to unwelcome effects on the kallikrein contact phase during CPB (since reduction of kallikrein activity by aprotinin has been shown to be beneficial) and may alter the hemostasis. We examined the effects of ACE inhibitors on intraoperative myocardial damage, kallikrein contact phase and hemostasis in patients undergoing CPB.. 47 patients randomly received either 20 mg/d enalapril or placebo. Creatine kinase (CK and CK-MB), lactate dehydrogenase (LDH), troponin T (TnT), thrombin-antithrombin III complex (TAT), fibrinogen and kallikrein-like activity were measured before surgery, during and immediately after CPB, at the end of surgery and 1, 3 and 5 days after surgery.. No significant differences between enalapril- and placebo- treated patients concerning CK (318 +/- 38.6 U/l vs. 316 +/- 16.8 U/l), CK-MB, LDH, TnT (1.81 +/- 0.45 ng/ml vs. 1.52 +/- 0.34 ng/ml), TAT, fibrinogen and kallikrein-like-activity could be found during study period.. Reduction of ischemic injury during CPB is not achieved with ACE inhibitors. However, treatment of patients with ACE inhibitors before and during CPB is fully feasible without side effects affecting the kallikrein contact phase or significant influence on hemostasis.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Bypass; Coronary Disease; Double-Blind Method; Enalapril; Female; Fibrinogen; Heart; Hemostasis; Humans; Intraoperative Complications; Kallikrein-Kinin System; Male; Middle Aged; Myocardial Reperfusion Injury

We sought to study the effect of angiotensin-converting enzyme inhibition on exercise-induced myocardial ischemia.. Although angiotensin-converting enzyme inhibitors have been shown to reduce ischemic events after myocardial infarction, few data are available regarding their direct anti-ischemic effects in patients with coronary artery disease.. We studied 43 patients (average age 63 +/- 8 years) with exercise-induced myocardial ischemia (> or =0.1 mV ST depression, despite optimal beta blockade) and normal left ventricular function (ejection fraction >0.50). In a double-blind, placebo-controlled parallel design, patients were treated with angiotensin-converting enzyme inhibitor (enalapril 10 mg twice daily) or placebo. Assessments were made after three weeks (short-term) and 12 weeks (long-term).. At baseline, the groups were well matched for all clinical characteristics. After three weeks, there was a slight but not significant increase in time to 0.1 mV ST depression in both groups (p = NS); rate pressure product (RPP = heart rate x systolic blood pressure) was also unaffected. After 12 weeks, however, time to 0.1 mV ST depression further increased in the enalapril group (5.6 +/- 1.9 min) but was unchanged in the placebo group (4.4 +/- 1.3 min; p < 0.05 between groups). In contrast, RPP was not affected. Concentrations of both atrial and brain natriuretic peptides at peak exercise tended to be lower by enalapril, if compared to placebo (p = NS).. Angiotensin-converting enzyme inhibition may reduce exercise-induced myocardial ischemia in patients with normal left ventricular function. Further studies are needed to elucidate the mechanisms involved.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Coronary Disease; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Enalapril; Exercise Test; Humans; Male; Middle Aged; Treatment Outcome; Ventricular Function, Left

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Coronary Disease; Enalapril; Female; Follow-Up Studies; Humans; Macrophage Colony-Stimulating Factor; Male; Middle Aged

To determine the effect of angiotensin-converting enzyme (ACE) inhibition on brachial flow-mediated vasodilation.. Quinapril, an ACE inhibitor with high affinity, has been shown to improve coronary endothelial dysfunction in patients with coronary artery disease. The effectiveness of different vasoactive agents to improve human endothelial function is unknown.. High resolution ultrasound was used to assess endothelium-dependent brachial artery flow-mediated vasodilation (FMD) in patients with coronary disease. We studied 80 patients (mean age 58 +/- 0.9 years) in a partial-block, cross-over design trial. Patients were randomized to one of four different drug sequences to receive quinapril 20 mg, enalapril 10 mg, losartan 50 mg or amlodipine 5 mg daily. Each patient received three drugs with a two-week washout period between treatments. The primary end point was the absolute difference in FMD after eight weeks of each study drug compared with their respective baselines analyzed in a blinded fashion.. There was mild impairment of FMD at baseline (7.3 +/- 0.6%). The change in FMD from baseline was significant only for quinapril (1.8 +/- 1%, p < 0.02). No change was seen with losartan (0.8 +/- 1.1%, p = 0.57), amlodipine (0.3 +/- 0.9%, p = 0.97) or enalapril (-0.2 +/- 0.8%, p = 0.84). No significant change in nitroglycerin-induced dilation occurred with drug therapy. The improvement in quinapril response was not seen in those with the DD ACE genotype (0.5 +/- 2.1%) but was seen in those with the ID and II genotype (3.3 +/- 1.2 and 3.2 +/- 1.9%, respectively, p = 0.03).. Only quinapril was associated with significant improvement in FMD, and this response is related to the presence of the insertion allele of the ACE genotype.

Topics: Aged; Amlodipine; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Blood Flow Velocity; Calcium Channel Blockers; Coronary Circulation; Coronary Disease; Drug Therapy, Combination; Enalapril; Endothelium, Vascular; Female; Humans; Isoquinolines; Losartan; Male; Middle Aged; Quinapril; Tetrahydroisoquinolines; Vasodilation

Endothelial dysfunction is an early event in atherosclerotic disease that precedes clinical manifestations and complications. The noninvasive assessment of endothelial function in patients with risk factors undergoing clinical treatment is an important medical advance. In this setting, altered endothelial function in patients with coronary hypercholesterolemia and its modifications by treatment with enalapril and simvastatin, either separately or in combination, was assessed in the brachial artery in a randomized, double-blind, 2-period crossover study.. Thirty-eight patients were separated in 2 groups. Group 1 (18 patients, 3 female, mean age 63 +/- 6.0 years) received simvastatin 10 mg/d for 8 weeks and simvastatin plus enalapril 5 mg/d for another 8 weeks. Group 2 (20 patients, 3 female, mean age 64 +/- 5.8 years) received enalapril 5 mg/d for 8 weeks and enalapril plus simvastatin 10 mg/d for another 8 weeks. All subjects underwent measurements of brachial artery diameter before and after postischemic hyperemia with high-resolution ultrasound at basal conditions (control) and under the effects of the drugs at the end of 8 and 16 weeks.. Cholesterol and LDL cholesterol levels significantly decreased with simvastatin treatment alone or with enalapril. Mean baseline arterial diameter was 5.24 +/- 1.25 mm in group 1 and 4.83 +/- 0.99 mm in group 2 (not significant). In group 1 after the first 8 weeks, endothelium-dependent vasodilation significantly increased with simvastatin treatment (control, 4.4%; 8 weeks, 7.6%; P <.001). After 16 weeks with the addition of enalapril, a further increase in vasodilation was seen (8.6%, P <.05 vs 8 weeks). In group 2, with enalapril treatment an increase in vasodilation versus control was seen (control, 4.3%; 8 weeks, 5.8%; P <.01). After 16 weeks, with the addition of simvastatin an additional increase in vasodilation was observed (9.1%, P <.001 vs 8 weeks). After nitroglycerin, vasodilation in group 1 at control, 8, and 16 weeks was 17%, 17.5%, and 18%, respectively. In group 2, nitroglycerin vasodilation at control, 8, and 16 weeks was 21%, 21%, and 22%, respectively.. Simvastatin significantly increased the postischemic vasodilator response in patients with coronary hypercholesterolemia, either as single treatment or added to enalapril. Similarly, the response was increased by enalapril, either alone or while simvastatin was being administered. Both drugs improve vasodilation and additive effects appear to be present.

Topics: Angiotensin-Converting Enzyme Inhibitors; Brachial Artery; Cholesterol; Coronary Disease; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Enalapril; Endothelium, Vascular; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Simvastatin; Ultrasonography; Vasodilation

The purpose of this study was to investigate the significance of the possible negative interaction between aspirin and angiotensin-converting enzyme (ACE) inhibitors.. Several provocative reports have recently suggested that aspirin is unsafe in patients with heart failure and has negative interaction with ACE inhibitors that might attenuate their beneficial effects upon survival.. We analyzed mortality data of 11,575 patients with coronary artery disease screened for the Bezafibrate Infarction Prevention trial. A total of 1,247 patients (11%) were treated with ACE inhibitors. Of them, 618 patients (50%) used aspirin.. Five-year mortality was lower among patients on ACE inhibitors and aspirin than patients on ACE inhibitors without aspirin (19% vs. 27%; p < 0.001). After adjusting for confounders, treatment with aspirin and ACE inhibitors remained associated with lower mortality risk than using ACE inhibitors only (relative risk [RR] = 0.71; 95% confidence interval [CI] = 0.56 to 0.91). Subgroup analysis of 464 patients with congestive heart failure treated with ACE inhibitors revealed 221 patients (48%) on aspirin and 243 patients not on aspirin. Although clinical characteristics and therapy were similar, patients taking aspirin experienced lower mortality than patients who did not (24% vs. 34%; p = 0.001). After adjustment, treatment with aspirin was still associated with lower mortality (RR = 0.70; 95% CI = 0.49 to 0.99).. Among coronary artery disease patients with and without heart failure who are treated with ACE inhibitors, the use of aspirin was associated with lower mortality than treatment without aspirin. Our findings contradict the claim that aspirin attenuates the beneficial effect of ACE inhibitors and supports its use in patients with coronary artery disease treated with ACE inhibitors.

Topics: Angiotensin-Converting Enzyme Inhibitors; Aspirin; Captopril; Coronary Disease; Cross-Over Studies; Drug Interactions; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Humans; Israel; Male; Middle Aged; Platelet Aggregation Inhibitors; Registries; Risk Factors; Survival Rate

This study sought to evaluate the relation between antiplatelet agent (APA) use and survival and morbidity from cardiac disease in patients with left ventricular (LV) systolic dysfunction.. APAs play an important role in the prevention and treatment of coronary disease. Their effects in patients with LV systolic dysfunction are unknown.. We reviewed data on APA use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between their use and all-cause mortality as well as the combined end point of death or hospital admission for heart failure (HF). We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between APA use and selected patient variables in relation to outcome.. APA use (46.3% of patients) was associated with significantly reduced mortality from all causes (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.73 to 0.92, p = 0.0005) and reduced risk of death or hospital admission for HF (adjusted HR 0.81, 95% CI 0.74 to 0.89, p < 0.0001) but was not influenced by trial assignment, gender, LV ejection fraction, New York Heart Association class or etiology. A strong interaction was observed among APA use, randomization group and all-cause mortality. The association between APA use and survival was not observed in the enalapril group, nor was an enalapril benefit on survival detectable in patients receiving APAs at baseline. However, randomization to enalapril therapy significantly reduced the combined end point of death or hospital admission for HF in APA users.. In patients with LV systolic dysfunction, use of APAs is associated with improved survival and reduced morbidity. This association is retained after adjustment for baseline characteristics. APA use is associated with retained but reduced benefit from enalapril.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiac Output, Low; Cause of Death; Cohort Studies; Confidence Intervals; Coronary Disease; Death, Sudden, Cardiac; Double-Blind Method; Enalapril; Female; Follow-Up Studies; Humans; Male; Middle Aged; Odds Ratio; Patient Admission; Placebos; Platelet Aggregation Inhibitors; Regression Analysis; Risk Factors; Sex Factors; Stroke Volume; Survival Analysis; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

The Prevention of Events with Angiotensin-Converting Enzyme Inhibition (PEACE) trial is an 8,100 patient, randomized, double-blind, placebo-controlled trial designed to determine the usefulness of angiotensin-converting enzyme (ACE) inhibitors in treating coronary patients with preserved left ventricular ejection fraction. The hypothesis being tested in this trial is that patients with coronary disease and ejection fraction > or =40% who are treated with ACE inhibitors will experience a reduction in the incidence of cardiovascular death, nonfatal myocardial infarction, or a revascularization procedure compared with patients treated with conventional therapy. The design of the PEACE trial is described herein.

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Coronary Angiography; Coronary Disease; Double-Blind Method; Echocardiography; Enalapril; Female; Follow-Up Studies; Humans; Male; Middle Aged; Safety; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Investigators from the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) previously reported that the isradipine group had a higher incidence of cardiovascular disease (CVD) events than the diuretic group. The ultimate objective of the analyses presented here was to assess how indices of glycemia (specifically, serum glucose, serum insulin, and HbA1c) might have influenced the effects of the two agents on blood pressure control and CVD events.. Inclusion criteria included men and women > or = 40 years of age with ultrasonographically confirmed carotid atherosclerosis and a diastolic blood pressure of > 90 mmHg. Although insulin-dependent diabetic patients were excluded, the three glycemia indices had wide enough ranges to include patients who may be classified as prediabetic. A total of 883 patients were randomized either to the dihydropyridine calcium antagonist (CA) isradipine (2.5-5 mg twice a day) or to the diuretic hydrochlorothiazide (12.5-25 mg twice a day) and followed in double-blind fashion for 3 years.. Both treatment groups had achieved comparable control of diastolic blood pressure, and there were no statistically significant differences in any of the glycemia indices, either at baseline or during follow-up. However, the excess isradipine events were noted to be clustered among those patients with elevated baseline levels of HbA1c who also experienced greater blood pressure reductions during follow-up.. The increased cardiovascular risk associated with dihydropyridine CAs in prediabetic patients may be an explanation for the overall CA debate.

Topics: Antihypertensive Agents; Blood Glucose; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; Coronary Disease; Diabetic Angiopathies; Double-Blind Method; Enalapril; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hydrochlorothiazide; Hypertension; Insulin; Isradipine; Male; Prediabetic State; Time Factors

This study was designed to investigate the possible mechanisms whereby enalapril improves cardiac function and mortality in chronic heart failure. We explored potential mechanisms by following 41 patients with early heart failure over the course of 1 year. These patients were randomized in a prospective triple-blind manner to receive either enalapril or placebo. Over the 1 year, repeated measurements were obtained of echocardiographic parameters, glomerular filtration rate, renal blood flow, hematocrit, plasma neurohormones, and QTc dispersion. Echocardiographic parameters improved with enalapril but deteriorated with placebo (cardiac output 4.6 +/- 1.6 to 3.7 +/- 1.5 L/min with placebo, and 4.5 +/- 1.3 to 5.8 +/- 2.0 L/min with enalapril; p <0.01). In contrast, there were no significant changes in renal blood flow (518 +/- 185 to 509 +/- 180 ml/min/1.73 m2 with placebo, and 541 +/- 142 to 504 +/- 162 ml/min/1.73 m2 with enalapril). Glomerular filtration rate changed from 79 +/- 20 to 78 +/- 19 ml/min/1.73 m2 with placebo, and from 85 +/- 21 to 73 +/- 27 ml/min/1.73 m2 with enalapril (p = 0.051). Enalapril reduced hematocrit (0.414 +/- 0.041 to 0.377 +/- 0.040%) significantly more than placebo (0.420 +/- 0.029 to 0.411 +/- 0.023 l/l; p <0.01). In addition, enalapril produced a marked reduction in QTc dispersion (93 +/- 36 to 88 +/- 28 ms with placebo and 93 +/- 35 to 60 +/- 22 ms with enalapril; p <0.05). Thus, enalapril significantly reduced hematocrit and reduced QTc dispersion in early heart failure. Both of these effects, but especially the latter, could be an important mechanism for the reduced mortality seen with angiotensin-converting enzyme inhibitors in heart failure. In contrast, renal hemodynamics did not parallel either the placebo-induced deterioration in cardiac function or the enalapril-induced improvements in cardiac function.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Coronary Disease; Double-Blind Method; Drug Therapy, Combination; Echocardiography; Electrocardiography; Enalapril; Female; Heart Failure; Hematocrit; Hemodynamics; Humans; Male; Middle Aged; Neurosecretory Systems; Prospective Studies; Treatment Outcome

This study determines the long-term efficacy of the ACE inhibitor, enalapril, in reducing the progression of microalbuminuria to clinical albuminuria in normotensive patients with type 2 diabetes.. There were 103 normotensive type 2 diabetic patients with persistent albumin excretion rate (AER) 20-200 micrograms/min and normal renal function followed for 5 years in a prospective randomized single-blind placebo-controlled trial. AER, blood pressure, fasting plasma glucose, and HbA1 were measured very 3-4 months and glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary urea every 12 months.. In the patients treated with enalapril, AER decreased from 55 +/- 33 to 20 +/- 59 micrograms/min (geometric mean +/- SD), whereas in the placebo group, AER increased from 53 +/- 31 to 85 +/- 90 micrograms/min after 5 years. Within 5 years, 7.7% (4/52) of enalapril-treated subjects and 23.5% (12/51) of placebo-treated subjects progressed to clinical albuminuria defined as AER > 200 micrograms/min and at least 34% above baseline (risk reduction = 66.7%, P < 0.001). AER increased at an annual rate of 12.3% (95% CI 9.8-14.9) in the placebo group, while it declined by 16.7% (95% CI -18.3 to -15.2) in the enalapril group (P < 0.001). In addition, 8 of the 12 placebo-treated patients had evidence of coronary artery disease. The rest of the parameters remained practically unchanged in the two groups.. After 5 years of therapy with enalapril, compared with placebo, normotensive subjects with type 2 diabetes experienced significantly less progression of microalbuminuria to clinical albuminuria, reduced AER, and preserved GFR.

Topics: Adult; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Blood Pressure; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Dietary Proteins; Disease Progression; Enalapril; Energy Intake; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Placebos; Risk Factors; Single-Blind Method; Time Factors

The present study was designed to evaluate the effects of early angiotensin converting enzyme (ACE) inhibition on left ventricular enlargement in patients with anterior wall infarction following reperfusion therapy.. Seventy-one consecutive patients with an anterior wall myocardial infarction were randomly allocated to enalapril (n = 36) or placebo (n = 35). All patients received either thrombolytic therapy (n = 46) or underwent primary coronary angioplasty (n = 25). Medication was started within 48 h admission to hospital and continued for 48 weeks. The process of left ventricular remodelling was assessed with two-dimensional echocardiography at 3 weeks and 1 year after the acute onset, and was related to the severity of the residual stenosis of the infarct-related artery.. Baseline left ventricular ejection fraction was 39.2% +/- 8.7%. During the study period left ventricular end-diastolic volume index increased from 48.2 +/- 9.9 ml.m-2 to 54.6 +/- 12.2 ml.m-2 at 3 weeks, and to 59.4 +/- 17.0 ml.m-2 after 1 year I control patients (P < 0.001). In the enalapril-treated patients, left ventricular end-diastolic volume index increased from 50.0 +/- 16.1 to 57.7 +/- 19.3 ml.m-2 at 3 weeks, and to 61.9 +/- 22.7 ml.m-2 after 1 year (P < 0.001). Both at 3 weeks and after 1 year, no overall differences in left ventricular volumes were observed between the enalapril and the placebo group (both ns). However, patients with a residual stenosis severity of > or = 70% in the infarct-related artery (n = 43) showed significant attenuation of remodelling by enalapril (n = 22) when compared to placebo (n = 21). In patients on enalapril, left ventricular end-diastolic volume index increased from 47.0 +/- 13.0 to 53.7 +/- 17.7 ml.m-2 compared to 48.0 +/- 9.6 to 60.3 +/- 16.3 ml.m-2 in control patients (P < 0.03). Also diastolic filling parameters were significantly improved in patients with > or = 70% residual stenosis.. In patients with an anterior wall infarction and a severe residual infarct-related coronary artery stenosis following reperfusion, treatment with enalapril prevents the process of left ventricular remodelling. As left ventricular dilatation is an early process we suggest that treatment with ACE inhibition should be started as soon as possible in this group of patients.

Topics: Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Coronary Disease; Double-Blind Method; Enalapril; Female; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Myocardium; Prospective Studies; Ventricular Function, Left

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Anticholesteremic Agents; Colchicine; Combined Modality Therapy; Coronary Angiography; Coronary Disease; Drug Therapy, Combination; Enalapril; Female; Humans; Lovastatin; Male; Middle Aged; Pilot Projects; Recurrence

To study the effects of adding a salicylate to the angiotensin converting enzyme inhibitor enalapril in patients with heart failure due to coronary artery disease.. Double blind, crossover study for three days in hospital followed by an extended similar study outside hospital over two months of once daily enalapril plus salicylate and enalapril plus placebo.. Tertiary referral centre.. 20 patients with heart failure due to myocardial infarction (New York Heart Association class II or III) and an ejection fraction less than 0.40. Twelve patients completed the two parts of the study.. Blood pressure, plasma converting enzyme activity; plasma angiotensin II and noradrenaline concentrations; excretion of metabolites of renal and systemic prostanoids.. The unloading effect of first and second dose of enalapril in the morning lasted only during the day; in the extended study it lasted 24 hours because of the drug's accumulation. Converting enzyme inhibitors attenuate the breakdown of bradykinin and therefore enhance prostaglandin E2 synthesis mediated by bradykinin. Evidence was found of such a prostaglandin E2 mediated contribution to ventricular unloading by enalapril, which was blocked by salicylate. The contribution, however, was small and variable, and salicylate addition had on average no significant de-unloading effect during the day. Unloading was abolished in only three of the 20 patients in the short term study and in one of the 12 in the extended study. At night, when other effects of enalapril on blood pressure had waned and the bradykinin induced effect persisted, salicylate significantly reduced the remaining small unloading effect. No effect was seen of salicylate addition on reversal of remodelling. Enalapril reduced angiotensin II induced synthesis of systemic and renal prostaglandin I2 and thromboxane A2, initially only during the day, but later also at night. It thereby masked suppression of thromboxane A2 synthesis by salicylate, which is the effect to which reinfarct prevention by salicylate is attributed.. The risk is low that salicylate will substantially reduce the benefit of enalapril in patients with heart failure by de-unloading the ventricle. Like other effects induced by bradykinin significant de-unloading occurs in only a minority of the patients. In the presence of enalapril, however, salicylate will probably not be as effective as expected in reducing reinfarction risk, because enalapril already reduces thromboxane A2 synthesis effectively in patients with heart failure and no further reduction by salicylate was found.

Topics: Adult; Aged; Angiotensin II; Blood Pressure; Coronary Disease; Creatinine; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Norepinephrine; Peptidyl-Dipeptidase A; Salicylates; Salicylic Acid

1. Angiotensin converting enzyme (ACE) inhibitors are in common use for the treatment of hypertension and heart failure. Whereas they are, in general, well tolerated, a dry cough can develop which, on occasion, requires termination of therapy. The reported prevalence of cough with ACE inhibitor therapy has varied from 0.2 to 25%, depending upon methods of data collection, analysis and symptom reporting. 2. To evaluate the prevalence of cough in Chinese patients receiving ACE inhibitors, interviews were carried out in 191 patients in Hong Kong who were taking therapy which included captopril or enalapril for hypertension or heart failure, and 382 patients matched for sex and age receiving alternative medications which excluded an ACE inhibitor (controls). Patients and controls were interviewed in a blinded manner by the same interviewer using a common adverse-effect questionnaire. 3. Persistent cough was reported in 44% of patients taking an ACE inhibitor (46% of those receiving captopril and 41.8% of patients taking enalapril), and in 11.1% of the controls (P < 0.001). The prevalence of other adverse reactions was similar, with no significant difference between the two treatment groups. The complication of cough was not related significantly to age, sex, underlying disease, drug dosage or smoking status. 4. This study indicates that cough is a common side effect of treatment with ACE inhibitors in Hong Kong Chinese, although in most patients cessation of therapy is not required. Whether Chinese are particularly susceptible to ACE-inhibitor cough requires a formal prospective study comparing Chinese and non-Chinese patients.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Chi-Square Distribution; Coronary Disease; Cough; Enalapril; Female; Hong Kong; Humans; Hypertension; Male; Middle Aged; New Zealand

Left ventricular function and neurohormonal status in patients with heart failure remaining symptomatic during therapy with angiotensin-converting enzyme inhibitors were assessed, and the effects of dopaminergic receptor stimulation in this setting were determined. Neurohormonal and left ventricular function (radionuclide angiography) data were obtained in 19 patients with symptomatic ischemic heart failure. Measurements were repeated after 4 to 6 weeks of therapy with the dopamine agonist ibopamine (100 mg, 3 times/day) or placebo administered in a double-blind, randomized, parallel group design. At baseline, despite therapy with enalapril, the angiotensin II levels (mean 39.4 pg/ml; p < 0.01 vs controls) were significantly increased, as were plasma norepinephrine (497 +/- 240 pg/ml; p < 0.01 vs controls), endothelin-1, atrial natriuretic peptide and arginine vasopressin. Moreover, in comparison with pretreatment values, left ventricular ejection fraction had decreased substantially (-9.1%) in patients with plasma norepinephrine > or = 600 pg/ml, but not in those with lower values of norepinephrine. With ibopamine, plasma norepinephrine decreased from 516 +/- 241 to 391 +/- 208 pg/ml (n = 8; p < 0.025 vs placebo), whereas it increased with placebo. In conclusion, the neurohormonal control provided by an angiotensin-converting enzyme inhibitor is reduced in a large subset of patients during prolonged therapy; ibopamine appears to be a potentially useful drug to improve neurohormonal control in this setting.

Topics: Aged; Coronary Disease; Deoxyepinephrine; Dopamine Agents; Double-Blind Method; Down-Regulation; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Norepinephrine; Receptors, Dopamine; Ventricular Function, Left

In a randomized double-blind, placebo-controlled, crossover trial, the potential anti-ischaemic action of the angiotensin-converting enzyme (ACE) inhibitor spirapril was studied in 19 patients with coronary artery disease (CAD) and reproducible exercise-induced ST-segment depression, but without hypertension or congestive heart failure. Measurements of blood pressure and heart rate as well as exercise-testing were performed after 2 weeks of treatment each with placebo and spirapril. Anginal attacks and consumption of short-acting nitrates were recorded in the patients' diaries. Resting blood pressure was not significantly reduced (143 +/- 20/89 +/- 10 mmHg vs 138 +/- 17/87 +/- 10 mmHg). The exercise-induced ST-segment depression, the main criterion for anti-ischaemic effect, was 2.17 +/- 1.72 mm after placebo and not significantly affected by spirapril (2.03 +/- 1.47 mm) despite a significant reduction in blood pressure x heart rate product at maximum workload (213 +/- 45.4 vs 197.5 +/- 36.8; p < 0.05). The number of anginal attacks per week and nitrate consumption remained virtually unchanged. A significant reduction of exercise-induced ischaemia in normotensive patients with CAD was not demonstrated with spirapril.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Coronary Disease; Double-Blind Method; Electrocardiography; Enalapril; Exercise Test; Heart Rate; Humans; Middle Aged

This study was undertaken to determine if a standard dose of aspirin interacts relevantly with the circulatory effects of enalapril in severe heart failure.. The frequent association of heart failure with coronary artery disease confers potential for combined treatment with an angiotensin-converting enzyme inhibitor and the prostaglandin synthesis inhibitor aspirin, the pharmacodynamic actions of which are, in part, mutually opposed.. In 18 patients, on 3 consecutive days, hemodynamic measurements were performed at baseline and 4 h after administration of a double placebo, enalapril (10 mg) plus placebo and enalapril plus aspirin (350 mg) according to a double-blind, randomized, crossover protocol.. Enalapril given before aspirin led to significant decreases in systemic vascular resistance, left ventricular filling pressure and total pulmonary resistance together with a significant increase in cardiac output. When given with or on the day after aspirin, enalapril did not elicit significant changes in any of these variables. There was a clear tendency to lower values for pulmonary artery pressure on all regimens, and slowing of the heart rate was incurred whether or not aspirin had been given. Chi-square analysis of the individual responses showed that the probability of effecting a decrease in systemic vascular resistance > or = 300 dynes.s.cm-5 was six times greater when enalapril was given without aspirin (p < 0.01).. In severe heart failure, the prostaglandin synthesis inhibition by aspirin counteracts the systemic arterial vasodilation of angiotensin-converting enzyme inhibition with enalapril and substantiates its dependence on the integrity of prostaglandin metabolism. Trends toward reductions of pulmonary artery pressure and slowing of the heart rate were still observed, presumably subsequent to lowered norepinephrine concentrations indicating maintenance of prostaglandin-independent actions of angiotensin-converting enzyme inhibition.

Topics: Adult; Aged; Aspirin; Chi-Square Distribution; Chronic Disease; Coronary Disease; Double-Blind Method; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Pulmonary Circulation; Pulmonary Wedge Pressure; Renin; Severity of Illness Index; Vascular Resistance

The Studies of Left Ventricular Dysfunction (SOLVD) trials were designed to evaluate the effects of enalapril on long-term mortality in patients with severe left ventricular (LV) dysfunction. Patients with LV ejection fractions less than or equal to 0.35 and symptoms of congestive heart failure (CHF) were enrolled in the treatment trial, whereas those with no history of overt CHF and taking no treatment directed for LV dysfunction were enrolled in the prevention trial. The baseline clinical characteristics of SOLVD patients were compared to characterize differences between patients in these 2 separate but concurrent trials. From over 70,000 patients screened with LV dysfunction, 4,228 patients were enrolled in the prevention trial and 2,569 patients in the treatment trial. Ischemic heart disease was the primary cause of LV dysfunction in both prevention (83%) and treatment (71%) trial patients. Prior myocardial infarction was present in 80% of the prevention and 66% of the treatment trial patients (p less than 0.001). In the prevention trial, infarction was recent (less than or equal to 6 months) in 27% patients and remote (greater than 6 months) in 57% patients. Treatment trial patients had proportionately more women (20 vs 13%; p less than 0.001) and non-Caucasians (20 vs 14%; p less than 0.001), as well as the coexisting risk factors of hypertension (42 vs 37%; p less than 0.001) and diabetes (26 vs 15%; p less than 0.001) than did prevention trial patients. Clinical characteristics of patients in both trials were influenced by the gender and race of enrolled patients. Similarly, coronary artery bypass surgery was performed less often in women and non-Caucasians.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Coronary Disease; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Racial Groups; Risk Factors; Sex Factors; Stroke Volume; Ventricular Function, Left

The effects of doxazosin (alpha-1-inhibitor) and enalapril (ACE-inhibitor) on blood pressure and exercise stress test were assessed in 10 hypertensive patients (8 M, 2 F, age 58 +/- 9 years) with coronary artery disease and exertional myocardial ischemia. A single blind, cross-over, placebo controlled trial was performed. Placebo was administered for 2 periods of 2 weeks, doxazosin and enalapril for at least 3 weeks. The sequence of the active drugs was randomized and the single daily dose, obtained by titration, was 7 +/- 5 mg for doxazosin and 18 +/- 13 mg for enalapril. Blood pressure measurements and treadmill tests (Bruce protocol) were performed at the end of each period. Rest systolic and diastolic pressures after placebo were respectively 173 +/- 15 and 106 +/- 9 mmHg and were reduced to 153 +/- 11 and 93 +/- 12 mmHg (p less than 0.05) after doxazosin and to 150 +/- 24 and 93 +/- 12 mmHg (p less than 0.05) after enalapril. Total exercise time was 473 +/- 91 s after placebo and increased to 545 +/- 84 s (p less than 0.05) after doxazosin and 529 +/- 100 s (p less than 0.05) after enalapril. Time to 1 mm ST depression (ST1) was 297 +/- 102 s after placebo and increased to 414 +/- 96 s (p less than 0.05) after doxazosin and to 396 +/- 133 s (p less than 0.05) after enalapril. Double product at peak exercise and at ST1 were respectively 26.3 +/- 2.8 and 22.1 +/- 2.8 x 10(3) and remained unchanged after enalapril and doxazosin. Peak exercise diastolic blood pressure was 107 +/- 5 mmHg after placebo, was reduced to 94 +/- 15 mmHg (p less than 0.05) after doxazosin and was unchanged after enalapril (101 +/- 10 mmHg, NS). Thus, doxazosin and enalapril induced a comparable decrease of rest blood pressure and a similar increase of exercise time in hypertensive patients with exertional myocardial ischemia. Doxazosin but not enalapril reduced exercise diastolic blood pressure.

Topics: Adrenergic alpha-Antagonists; Aged; Antihypertensive Agents; Coronary Disease; Doxazosin; Enalapril; Exercise Test; Female; Humans; Hypertension; Male; Middle Aged; Prazosin; Vasodilator Agents

The antihypertensive efficacy and safety of doxazosin and enalapril were compared in the general practice setting (n = 54). Both agents produced comparable, statistically significant (p less than 0.05) reductions in mean blood pressure with no clinically relevant changes in heart rate. Side effects in the two groups were mild or moderate and disappeared or were tolerated with continued treatment. Doxazosin, in contrast to enalapril, produced a significant (p less than 0.05) reduction in the total serum cholesterol concentration, a reduction in the level of triglycerides, and a favorable increase in the high-density lipoprotein/total cholesterol ratio. The reduction in calculated coronary heart disease risk produced by doxazosin (-27.58%) was highly significant (p less than 0.0002) and greater than that produced by enalapril (-18.49% p less than 0.02).

Topics: Antihypertensive Agents; Coronary Disease; Double-Blind Method; Doxazosin; Enalapril; Family Practice; Female; Germany, West; Humans; Hypertension; Lipids; Male; Middle Aged; Prazosin; Risk Factors

We present preliminary data of a study comparing captopril, a short acting, with lisinopril, a long acting ACE-inhibitor in 8 of 12 projected patients with severe chronic heart failure (NYHA III-IV) and one additional risk factor (e.g. diabetes mellitus, renal failure). The 8 patients were treated in a cross over design for 12 weeks with either drug. While lisinopril improved NYHA-class in all patients, captopril reached this goal in only 3. Renal function was stable in all patients. Captopril influenced hormones (renin, aldosterone, norepinephrine, epinephrine) and microalbuminuria less than lisinopril. The number of adverse reactions was smaller in lisinopril treated patients. These preliminary data demonstrate at least an equal efficacy of lisinopril compared to captopril in high risk patients with severe chronic heart failure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiomyopathy, Dilated; Coronary Disease; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Kidney Function Tests; Lisinopril; Male; Middle Aged

The long-term effect of enalapril (group 1) and captopril (group 2) on clinical symptomatology and left ventricular function was evaluated in 29 patients with severe congestive heart failure (13 ischemic and 12 dilated cardiomyopathy, four valvular heart disease). During the 6-month observation period, five patients died (two on enalapril and three on captopril therapy = 6-month mortality rate 18%). Nine patients showed no beneficial effect of enalapril or captopril on clinical and hemodynamic findings (= nonresponders). The initial findings on these nine patients were, however, not significantly different from the clinical and hemodynamic findings on the patients who improved. Enalapril had to be discontinued in two patients because of side effects (progressive renal failure and gastrointestinal symptoms, respectively). A total of 22 patients completed the study, 11 treated with enalapril (mean dosage 25 +/- 10 mg/day) and 11 treated with captopril (mean dosage 77 +/- 26 mg/day). After 6 months there was a significant improvement according to the New York Heart Association (NYHA) classification, from 2.4 to 1.9 in group 1 (p less than 0.01) and from 2.7 to 1.9 in group 2 (p less than 0.001). The cardio-thoracic ratio (chest x-ray) decreased significantly from 0.59 to 0.56 (p less than 0.001) in group 1 and from 0.56 to 0.53 (p less than 0.001) in group 2. Physical working capacity (bicycle ergometry) showed a significant increase in both groups from 61% to 81% in group 1 (p less than 0.01) and from 66% to 83% in group 2 (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Pressure; Captopril; Cardiac Output; Cardiomyopathy, Dilated; Coronary Disease; Enalapril; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic

We evaluated the cardiopulmonary exercise test results before and after long-term (16 weeks) treatment with the dihydropyridine calcium antagonist, felodipine (10 mg b.i.d., n = 9), and the ACE inhibitor, enalapril (10 mg b.i.d., n = 11), in 20 patients with New York Heart Association class III congestive heart failure. There were no significant differences at baseline. After 16 weeks patients in the enalapril group showed a significant increase in exercise duration and VO2max, without changes in arterial pressures and heart rate. In the felodipine group, exercise duration and VO2max did not change significantly, but arterial pressures and heart rate were significantly reduced at all exercise levels. Between group analysis showed a significant reduction in arterial pressures and heart rate in the felodipine group compared with enalapril, but no differences in aerobic capacity and exercise duration. These results demonstrate that felodipine and enalapril have essentially different effects on cardiopulmonary exercise results in patients with congestive heart failure.

Topics: Aged; Coronary Disease; Double-Blind Method; Drug Evaluation; Enalapril; Exercise Test; Felodipine; Heart Failure; Hemodynamics; Humans; Middle Aged

The effect of angiotensin converting enzyme inhibition on myocardial ischaemia was studied in 12 normotensive patients with chronic stable angina and exercise induced ST segment depression. The study was randomised, double blind, placebo controlled, and crossover with treatment periods of two weeks. Enalapril was used to inhibit angiotensin converting enzyme. Assessment was by angina diaries and maximum symptom limited treadmill exercise tests. The results for the whole group showed a significant reduction in systolic blood pressure at rest and at peak exercise. Mean total exercise duration was 466 s (95% confidence interval 406 to 525) when the patients were taking placebo and 509 s (436 to 583) when they were taking enalapril. Four patients prolonged their total exercise time (mean 450 to mean 591 s) by more than 20%. Two patients, however, developed ischaemia earlier on exercise and reduced their total exercise duration (mean 490 to mean 390 s). Although angiotensin converting enzyme inhibition tended to reduce myocardial ischaemia in the group as a whole, some patients improved while others deteriorated. Thus the effects of enalapril are variable and this may have important implications when enalapril is used to treat heart failure in patients with underlying severe ischaemic heart disease.

Topics: Aged; Angina Pectoris; Chronic Disease; Coronary Circulation; Coronary Disease; Double-Blind Method; Enalapril; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Nitroglycerin; Random Allocation

The anti-anginal effect of the ACE inhibitor enalapril, at a dosage of 5 mg twice a day, was tested in a randomised, placebo-controlled double-blind trial on 12 normotensive patients with proven coronary-heart disease. There was a reduction of exercise-induced ST depression by 22% already after the first dose of 5 mg. After 15 days of treatment the ST depression had decreased by 35% (P less than 0.05).

Topics: Adult; Aged; Blood Pressure; Clinical Trials as Topic; Coronary Disease; Double-Blind Method; Enalapril; Exercise Test; Humans; Middle Aged; Placebos; Random Allocation

Topics: Clinical Trials as Topic; Coronary Disease; Enalapril; Humans; Research Design

To analyse 2-year hospitalization and cost data collected during a prospective, double-blind, randomized, controlled trial comparing amlodipine, enalapril and placebo in normotensive patients with coronary artery disease (CAD).. All patients who were enrolled in the CAMELOT study were included in this economic substudy. Patients with CAD and normal blood pressure were randomized to amlodipine, enalapril or placebo, and followed up for 24 months (between 1999 and 2004). Data on hospitalizations and medication use were obtained from the clinical trial. Costs were assigned from secondary sources. Total costs ($US, year 2004 values) were estimated as the sum of costs associated with cardiovascular hospitalizations, study medications and concomitant cardiovascular medications. Costs and resource use were analysed by treatment arm overall and for selected patient subgroups. Cost differences were evaluated using nonparametric bootstrap techniques.. Of 1991 patients enrolled, 663 were treated with amlodipine, 673 were treated with enalapril and 655 were treated with placebo. Significantly fewer patients were hospitalized for cardiovascular reasons in the amlodipine group (16.4%) than in the placebo group (22.7%; p < 0.01), but not compared with the enalapril group (20.1%; p = 0.09). The amlodipine group also had numerically fewer days in hospital per patient (1.1) than the enalapril (1.3) and placebo (1.5) groups. Mean 2-year per-patient costs in the amlodipine group were estimated to be $US 609 and $US 717 lower than for the placebo and enalapril groups, respectively.. These results suggest that use of amlodipine may reduce costs of care among CAD patients with normal blood pressure.

Topics: Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Calcium Channel Blockers; Confidence Intervals; Coronary Disease; Costs and Cost Analysis; Data Interpretation, Statistical; Enalapril; Female; Follow-Up Studies; Health Care Costs; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Multicenter Studies as Topic; Placebos; Randomized Controlled Trials as Topic; Statistics, Nonparametric; Time Factors

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Cardiovascular Agents; Coronary Disease; Echocardiography; Enalapril; Humans; Middle Aged; Patient Selection; Randomized Controlled Trials as Topic; Risk Factors; Vasodilator Agents

Drug therapy of coronary heart disease (CHD) is a life-long treatment. With every change from in-patient to out-patient care and back, changes in medication may occur. If a drug is chosen which provides no proven long-term benefit in terms of reduced morbidity and mortality, the expected therapeutic benefit may be missed. We investigated in 224 patients admitted to the medical departments of two hospitals (one with a specialized Cardiology Unit, one with a General Internal Medicine Unit) the prescriptions for CHD by the general practitioner before admittance into the hospital, the prescriptions recommended at the time of discharge, and the prescriptions made by the general practitioner three months after discharge. Of the drug classes with proven effects on morbidity and mortality (acetylsalicylic acid, beta-blockers, statins, ACE inhibitors), none had sufficiently high prescription rates. Prescription rates at discharge were 30% for beta-blockers and statins, 70% for acetylsalicylic acid, and 60% for ACE inhibitors. Only in patients with acute myocardial infarction were the prescription rates for these drug classes higher at this time point. The presence of contraindications was not of prime importance for the low prescription rates, as even in patients without contraindications prescription rates were not significantly higher than in the total patient cohort. Out of the patients with hypercholesterolemia, one third of those treated in the Cardiology Department and two thirds of those treated in the General Internal Medicine Department were not given any lipid-lowering medication. Prescription rates for those drug classes that provide symptomatic relief but have little impact on mortality rates (calcium channel blockers, nitrates) were high in both hospitals. The present study shows that evidence-based guidelines for the drug treatment of coronary heart disease are not adequately put into practice.

Topics: Adrenergic beta-Antagonists; Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Captopril; Coronary Disease; Drug Prescriptions; Enalapril; Evidence-Based Medicine; Female; Guideline Adherence; Humans; Hypolipidemic Agents; Inpatients; Male; Middle Aged; Myocardial Infarction; Nitrates; Outpatients; Platelet Aggregation Inhibitors; Practice Guidelines as Topic

Topics: Acrylates; Antihypertensive Agents; Coronary Disease; Enalapril; Humans; Hypertension; Imidazoles; Risk Factors; Stroke; Systole; Thiophenes; Treatment Outcome

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Coronary Disease; Enalapril; Heart Transplantation; Losartan; Models, Animal; Postoperative Complications; Rats; Rats, Inbred F344; Rats, Inbred Lew; Receptor, Angiotensin, Type 1; Vascular Diseases

Angiotensin II is one of the most potent mitogens of smooth muscle cell proliferation and plays a central role in the development of accelerated coronary artery disease (ACAD), which remains a serious consequence after heart transplantation and limits long-term survival. We investigated the effect of an angiotensin-II blocker, Losartan (angiotensin II Type 1 [AT(1)]-blocker), and an angiotensin-converting enzyme (ACE) inhibitor, Enalapril, on experimental ACAD in a rat cardiac transplant model (Fisher to Lewis).. After grafting, recipients were treated with 10 mg/kg/day per os Losartan or 40 mg/kg/day per os Enalapril. Two groups of animals received additional pre-treatment with Losartan or Enalapril 7 days before transplantation. All study groups, including the control group, received immunosuppression with cyclosporine (3 mg/kg/day sub-cutaneously). We assessed the extent of ACAD of large and small arteries 80 days after grafting using digitizing morphometry.. We observed significant reduction of neointimal proliferation in small arteries in Losartan pre- and post-treated and in Enalapril pre-treated recipients compared with the cyclosporine-treated group (p < 0.05). In epicardial arteries, Enalapril pre- and post-treatment as well as Losartan post-treatment significantly reduced neointimal formation compared with the control group. Reduction of neointima by Enalapril post-treatment in small arteries and Losartan pre-treatment in large arteries trended toward but failed statistical significance.. Our results suggest the important role of the renin-angiotensin system in neointimal proliferation, which can be reduced equally with ACE inhibitors or the angiotensin-II blocker. Therefore AT(1) blockade with Losartan is a useful therapeutic strategy for inhibition of ACAD after cardiac transplantation.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Coronary Disease; Coronary Vessels; Cyclosporine; Enalapril; Graft Rejection; Graft Survival; Heart Transplantation; Immunosuppressive Agents; Losartan; Male; Premedication; Rats; Rats, Inbred F344; Rats, Inbred Lew; Transplantation, Heterotopic

Topics: Abciximab; Alanine; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Antibodies, Monoclonal; Aspirin; Benzamidines; Biphenyl Compounds; Cardiology; Cardiovascular Agents; Clinical Trials as Topic; Clopidogrel; Combined Modality Therapy; Coronary Disease; Dalteparin; Defibrillators, Implantable; Double-Blind Method; Enalapril; Endothelial Growth Factors; Fatty Acids, Omega-3; Guanidines; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunoglobulin Fab Fragments; Laser Therapy; Lymphokines; Metoprolol; Multicenter Studies as Topic; Myocardial Revascularization; Platelet Aggregation Inhibitors; Pyrrolidines; Randomized Controlled Trials as Topic; Simvastatin; Sodium-Hydrogen Exchangers; Stents; Sulfones; Thrombolytic Therapy; Ticlopidine; Tissue Plasminogen Activator; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Vitamin E

The effect of angiotensin-converting enzyme (ACE) inhibitors on ischemia-induced spatial dispersion of ventricular repolarization was investigated in 12 pentobarbitone-anesthetized sheep. The obtuse marginal coronary artery was occluded in the pretreated animals (enalapril maleate, 0.4 mg/kg, i.v., n = 6) and controls (normal saline, i.v., n = 6). The activation-recovery intervals were determined from the unipolar ECGs acquired from the ischemic region. There was a significant increase in the pooled activation-recovery interval dispersion in both groups at 30 min of coronary occlusion (p < 0.01), however, the increase in the treatment group was smaller than that of the controls (15.9 +/- 9.7 vs. 43.6 +/- 19.9 ms, p < 0. 01). Ventricular ectopic beats were observed in the 6 controls and in only 1 pretreated animal.. ACE inhibitors suppress the spatial dispersion of ventricular repolarization and this may be attributed to, at least in part, its antiarrhythmic effect.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Arrhythmias, Cardiac; Coronary Disease; Electrocardiography; Enalapril; Female; Male; Myocardial Ischemia; Sheep; Ventricular Function; Ventricular Premature Complexes

To investigate the effects of enalapril, an angiotensin-converting enzyme inhibitor, on nitrate tolerance during continuous nitrate therapy, coronary artery diameters and platelet cyclic guanosine monophosphate (cGMP) levels were measured before and 2 minutes after intracoronary injection of nitroglycerin 200 microg in 60 patients with coronary artery disease and were compared among 20 patients treated with nitrates (nitrate group), 20 patients treated with both nitrates and enalapril (enalapril group), and 20 untreated patients (control group). The percent increase in platelet cGMP and coronary dilatation in the nitrate group was significantly less than in the control group, but the percent increase in the enalapril group was significantly greater than that in the nitrate group. These results indicate that enalapril may be helpful as concomitant therapy to maintain the effect of nitrates during continuous nitrate therapy.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Platelets; Case-Control Studies; Coronary Angiography; Coronary Disease; Coronary Vessels; Cyclic GMP; Drug Administration Schedule; Enalapril; Female; Humans; Hypertension; Isosorbide Dinitrate; Male; Middle Aged; Nitroglycerin; Norepinephrine; Renin; Vasodilator Agents

Topics: Angiotensin-Converting Enzyme Inhibitors; Coronary Disease; Enalapril; Heart Failure; Humans; Prognosis; Ventricular Dysfunction, Left

Topics: Angiotensin-Converting Enzyme Inhibitors; Coronary Disease; Enalapril; Humans; Myocardial Infarction; Ventricular Function, Left

Topics: Aged; Anticholesteremic Agents; Aspirin; beta Carotene; Carotenoids; Cholesterol, Dietary; Coronary Disease; Diet, Fat-Restricted; Diltiazem; Drug Therapy, Combination; Enalapril; Humans; Lovastatin; Male; Simvastatin; Tomography, Emission-Computed; Vitamins

Topics: Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Captopril; Coronary Disease; Diltiazem; Enalapril; Female; Heart Transplantation; Humans; Hyperplasia; Lisinopril; Male; Middle Aged; Nifedipine; Transplantation, Homologous; Tunica Intima; Ultrasonography, Interventional; Verapamil

Topics: Adrenergic beta-Antagonists; American Heart Association; Angioplasty, Balloon, Coronary; Coronary Disease; Enalapril; Humans; Oligopeptides; Peptides, Cyclic; Platelet Membrane Glycoproteins; Randomized Controlled Trials as Topic; Somatostatin; Stents; Thrombolytic Therapy

The purpose of the study was to evaluate the effect of enalapril on the frequency of ventricular premature beats in patients with congestive heart failure. The study group consisted of 30 patients with a mean age of 47 +/- 0.6 years with chronic congestive heart failure (NYHA classes III and IV) due to primary dilated cardiomyopathy and cardiomyopathy in the course of ischaemic heart disease. Initial therapy with digitalis and diuretics was supplemented with enalapril at a dose of 5-20 mg daily. Initially and at three months after enalapril, the following parameters were evaluated: NYHA functional class, the presence of premature ventricular beats in 24-hour ECG recording and left ventricular function by echocardiography. The scheduled therapy was completed by 23 patients; in 5 patients, the intake was discontinued because of hypotension, one patient died after 14 days due to worsening heart failure, and one patient was submitted for pacemaker implantation. Clinical improvement manifesting itself by a shift to lower NYHA classes was found in 20 patients. A reduced number of premature ventricular beats was observed in 52% of the patients. Termination of cardiac arrhythmias, especially of complex beats, was parallel to the circulatory improvement.

Topics: Adult; Cardiac Complexes, Premature; Cardiac Output; Cardiomyopathy, Dilated; Coronary Disease; Echocardiography; Electrocardiography, Ambulatory; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged

Among the interventions designed to limit postischemic oxidative injury, those that enhance the myocardial content of thiol groups are attractive because thiols are powerful antioxidant. Indeed, part of the protection afforded by the angiotensin-converting enzyme (ACE) inhibitor captopril in regional myocardial ischemia is attributed to its thiol group. This study assesses the effects of captopril in a surgically relevant model of global ischemic arrest. Thirty rats were implanted subcutaneously (s.c.) with osmotic pumps that allowed continuous delivery of captopril (total dose 75 mg), enalapril (a nonthiol-containing ACE inhibitor, total dose 7.5 mg) or saline in 48 h. Drug concentrations were equipotent in their effect on angiotensin I (ANGI) pressor response. Hearts were then excised, perfused under isovolumic conditions, and subjected to 90-min cardioplegic arrest at 30 degrees C followed by 1-h reperfusion. Pre- and postischemic coronary flows were significantly higher to a similar extent in the two drug-pretreated groups than in controls. However, captopril-pretreated hearts had the best recovery of contractility (dP/dtmax; 3,590 +/- 74 versus 2915 +/- 64 mm Hg s-1 in the enalapril group, p less than 0.001), and diastolic pressure (13.7 +/- 0.9 mm Hg vs. 20.0 +/- 1.6 mm Hg in the enalapril group, p less than 0.05). We conclude that pretreatment with ACE inhibitors improves myocardial recovery after cardioplegic arrest and that captopril is more effective than enalapril. The additional protection afforded by captopril was not flow mediated, suggesting that the cardioprotective effects of this drug not only involve an ACE inhibition-dependent coronary vasodilation but could be related to a thiol-dependent limitation of oxidative injury.

Topics: Animals; Captopril; Coronary Circulation; Coronary Disease; Diastole; Enalapril; Heart; Heart Arrest, Induced; Male; Myocardial Reperfusion Injury; Rats; Rats, Inbred Strains; Time Factors; Ventricular Function, Left

As a rule, left ventricular relaxation is impaired in patients with coronary artery disease and congestive heart failure. In addition, the passive elastic properties in early and late diastole change when the ventricle dilates. Diastolic properties of the left ventricle were studied in 11 patients with congestive heart failure class II-IV (NYHA) before and 3 months after 10-20 mg enalapril was added to their regimen of salt restriction, a diuretic and occasionally digitalis. Haemodynamic studies were performed using radionuclide angiography and simultaneous pressure-volume measurements. Systemic vascular resistance decreased from 1479 to 1182 dynes.s.-1 cm-5 (P < 0.05) and left ventricular end-diastolic pressure from 19.2 to 15.9 mmHg (P < 0.05). Left ventricular end-diastolic volume index decreased from 130 +/- 22 to 81 +/- 22 ml (P < 0.01). Indices of early diastolic relaxation, such as peak filling rate (1.43 +/- 0.46 to 1.49 +/- 0.84 EDV/s), time to peak filling rate (460 +/- 70 to 490 +/- 70 ms), peak negative dP/dt (-903 +/- 190 to -891 +/- 190 mmHg/s) and tau, the time constant of isovolumic pressure decay (58.7 +/- 14.4 to 48.4 +/- 15.2 ms) did not change significantly. In nine patients pressure-volume loops shifted to the left in all patients but one due to reduction in end-systolic and end-diastolic volume. The steepness of the diastolic part of the pressure-volume relationship increased, indicating an increase in chamber stiffness. The stiffness constant increased about 25% towards a more normal value. The alteration in stiffness seemed to be mainly due to the change of the geometry of the ventricle and not to a major change in the visco-elastic properties of the ventricular wall. In conclusion, regression of remodelling induced by enalapril does not change diastolic function parameters in patients with chronic congestive heart failure beyond the changes caused by regression of ventricular dilation.

Topics: Blood Pressure; Cardiac Catheterization; Cardiac Output; Cardiac Output, Low; Cardiac Volume; Coronary Disease; Diastole; Enalapril; Gated Blood-Pool Imaging; Heart Failure; Humans; Long-Term Care; Myocardial Contraction; Stroke Volume; Systole; Ventricular Function, Left

The chemiluminescence reaction elicited from luminol in the presence of hydroxyl radicals was concentration-dependently suppressed by captopril, indicating efficacious radical scavenging. As to be expected, ACE inhibitors lacking free sulfhydryl groups (ramipril, enalapril) were inactive. However, the endogenous scavenger and anti-oxidant uric acid proved to be far superior to captopril, when concentrations of both were compared that are realized in vivo. A substantial augmentation of endogenous scavenging ability during therapy with captopril thus seems unlikely. In a model of standardized myocardial hypoxia (isolated working heart of the guinea pig with 30 min low flow perfusion) captopril, ramiprilat and uric acid equally improved post-hypoxic heart function. There was no cardioprotective action of captopril in excess of that accountable for by inhibition of ACE. It seems possible that ACE (kininase II) inhibitors exert cardioprotection via elevated tissue levels of kinins: bradykinin also improved heart performance after low flow perfusion and bradykinin-induced coronary dilatation was markedly enhanced in the presence of ramiprilate, reflecting attenuated degradation by endothelial kininase II.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Bridged Bicyclo Compounds; Captopril; Coronary Disease; Dose-Response Relationship, Drug; Enalapril; Guinea Pigs; Hemodynamics; Hydroxides; Hydroxyl Radical; Luminescent Measurements; Myocardial Reperfusion Injury; Pyrroles; Ramipril; Sulfhydryl Reagents; Uric Acid

To determine whether angiotensin converting enzyme (ACE) inhibition may reduce the incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA), we retrospectively identified 322 consecutive patients who underwent a successful procedure from June 1988 to December 1989. No patients developed chest pain, ST segment elevation, positive cardiac enzymes, or other evidence of abrupt vessel closure following the PTCA. All patients received intravenous heparin after PTCA and aspirin was begun on the day prior to PTCA. Patients were separated into two groups: those at hospital discharge incidentally treated for hypertension or heart failure with ACE inhibitors (n = 36), and those treated with a drug regimen which did not include ACE inhibitors (n = 286). The two groups were similar with respect to age (61 +/- 13.5 vs. 60 +/- 12.5, p = NS) and other demographic characteristics. Restenosis, defined as the presentation to a physician with symptoms of angina within 6 months of the PTCA and the finding on repeat catheterization of a significant restenosis at the site of the PTCA, occurred in 30% of the patients who were discharged on a drug regimen which did not include ACE inhibitors vs. 3% (p less than .05) in those treated with an ACE inhibitor. Thus, it appears that the use of ACE inhibitors may significantly reduce the incidence of restenosis after successful PTCA.

Topics: Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Captopril; Combined Modality Therapy; Coronary Disease; Enalapril; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Lisinopril; Male; Middle Aged; Recurrence

Because beta-adrenergic blockade has as one of its many effects altered electrophysiological abnormalities after dogs with left ventricular hypertrophy have been subjected to coronary occlusion, we tested the hypothesis that metoprolol (200-400 mg/day) would reduce mortality rates in dogs with one-kidney, one clip left ventricular hypertrophy while a similar reduction in arterial pressure with enalapril (20-40 mg/day) would not. Dogs with left ventricular hypertrophy were given metoprolol or enalapril for 5-7 days before a 3-hour coronary occlusion. Infarct size and risk area were measured with triphenyltetrazolium chloride stain and barium angiography, respectively. For control (n = 15), left ventricular hypertrophy (n = 17), left ventricular hypertrophy plus metoprolol (n = 12), and left ventricular hypertrophy plus enalapril (n = 15) groups, mean arterial pressure, ratio of infarct size to risk area, and dogs experiencing sudden death were 110 +/- 4, 142 +/- 4, 121 +/- 7, and 120 +/- 3 mm Hg; 44 +/- 5%, 65 +/- 5%, 44 +/- 7%, and 30 +/- 4%; and 27%, 65%, 17%, and 53%, respectively. Thus, the excessive increase in early mortality occurring when dogs with hypertension and left ventricular hypertrophy undergo coronary occlusion is interrupted with beta-blockade, possibly via electrophysiological effects rather than by changes in arterial pressure or infarct size.

Topics: Adrenergic beta-Antagonists; Animals; Cardiomegaly; Coronary Circulation; Coronary Disease; Death, Sudden; Dogs; Enalapril; Female; Heart Ventricles; Hemodynamics; Hypertension; Male; Metoprolol; Myocardial Infarction; Risk Factors

The deranged autonomic control of heart rate was studied in 34 patients with heart failure (New York Heart Association [NYHA] functional class II to III) by examining the carotid sinus baroreflex. The carotid sinus baroreceptors were stimulated by graded suction. The slope of the regression line between increases in cycle length and the degree of neck suction was taken as an index of baroreflex sensitivity. The reflex response is mediated by a selective increase of vagal efferent activity. Baroreflex sensitivity therefore represents a measure of vagal reactivity. Using multiple regression analysis, baroreflex sensitivity (BS) correlated positively to stroke volume index (SVI) and inversely to plasma renin activity (PRA) and to age: BS = 0.47 SVI - 0.38 PRA - 0.23 age + constant (r = 0.74; p less than 0.0005). In addition to digitalis and diuretics, angiotensin-converting enzyme (ACE) inhibitors (captopril or enalapril) were given to 16 patients for a mean of 17 +/- 3 days. The patients with hemodynamic improvement (group A) exhibited improved baroreflex sensitivity (1.4 +/- 0.4 to 3.6 +/- 1.2 msec/mm Hg; p less than 0.01). Baroreflex sensitivity remained unchanged (3.1 +/- 0.8 to 2.4 +/- 1.0 msec/mm Hg; n.s.) in the patients without hemodynamic improvement (group B). The increase in reflex sensitivity did not correlate with hemodynamic alterations. Baroreflex sensitivity during ACE inhibition (BSD) was only related to the baseline baroreflex sensitivity (BSB): BSD = 2.8 BSB - 0.46 (r = 0.84; p less than 0.005). In patients with heart failure, reflex bradycardia decreases with age and with PRA and increases with stroke volume. Chronic therapy with ACE inhibitors enhances vagal reactivity in patients with hemodynamic improvement.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiomyopathy, Dilated; Carotid Sinus; Coronary Disease; Enalapril; Female; Humans; Male; Middle Aged; Pressoreceptors; Reflex; Vagus Nerve

A 65-year-old male with a long history of congestive heart failure presented to the emergency room with facial swelling 7 h after the first dose of enalapril. He was treated with diphenhydramine and hydrocortisone which improved his angioedema. However, there was a profound relapse of the angioedema followed by respiratory arrest. He suffered severe anoxic brain damage and died five days later. It is likely that the long half-life of enalapril lead to this rebound phenomenon. Enalapril induced angioedema is reviewed with suggestions for management.

Topics: Aged; Angioedema; Coronary Disease; Enalapril; Heart Failure; Humans; Hypoxia, Brain; Male; Respiratory Insufficiency

Topics: Adult; Coronary Disease; Enalapril; Female; Humans; Syncope

The protective effect of angiotensin-converting enzyme inhibitors (ACEI) on myocardial ischemia and reperfusion damage was estimated in rat hearts, both in vivo and in vitro. Enalapril 2.5 mg/kg ip pretreatment at 24 and 5 h before coronary occlusion, significantly blunted the rise of CPK (445 +/- 151 vs 649 +/- 244 mu/ml, P less than 0.05) and improved electrocardiogram (ECG) 8 h after coronary occlusion. In global ischemia and reperfusion ex vivo, enalapril improved contractility (0.9 +/- 0.2 vs 0.3 +/- 0.3 g, P less than 0.05) and coronary flow (15.6 +/- 3.3 vs 11.9 +/- 3.1 ml/min/g, P less than 0.05), shortened significantly the duration of reperfusion arrhythmia (3.1 +/- 2.7 vs 9.7 +/- 8.1 min, P less than 0.05). In Langendorffs heart, captopril remarkably preserved force of contraction (2.1 +/- 0.4 vs 1.4 +/- 0.4 g, P less than 0.01) and coronary flow (2.7 +/- 0.5 vs 3.6 +/- 0.9 ml/min/g, P less than 0.05) in segmental infarction deteriorated by angiotensin I. Captopril 10(-5) M infusion reduced the release of CPK (435 +/- 112 vs 640 +/- 123 mu/min coronary flow, P less than 0.05). This action was almost completely abolished by pretreating and infusing with indomethacin. As a positive control, prostacyclin 5 X 10(-7) M infusion further reduced the release of CPK to 330 +/- 77 mu/min. It is concluded that angiotensin-converting enzyme inhibitor can protect both myocardial ischemia and reperfusion damage in rat hearts. The mechanism of protection was ascribed to reduced production of angiotensin II by ACE inhibition and increased prostacyclin release in the myocardium.

Topics: Angiotensin I; Animals; Captopril; Coronary Circulation; Coronary Disease; Enalapril; Epoprostenol; Female; In Vitro Techniques; Male; Myocardial Contraction; Myocardial Infarction; Rats

Topics: Adrenergic alpha-Antagonists; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Captopril; Coronary Disease; Diazoxide; Drug Tolerance; Enalapril; Hemodynamics; Humans; Hydralazine; Hypertension; Minoxidil; Muscle, Smooth; Nitroglycerin; Vasodilator Agents

Enalapril, a new potent orally active angiotensin-converting enzyme inhibitor, was studied in cats subjected to acute myocardial ischemia. Enalapril, administered intravenously (2 mg/kg, plus 2 mg/kg/h) 30 min after ligation of the left coronary artery, significantly reduced the pressure-rate index, an indicator of myocardial oxygen demand. This was confirmed in isolated cat papillary muscles where enalapril reduced contractile force by 5-10%. During myocardial ischemia, enalapril reversed the elevated S-T segment of the electrocardiogram toward normal 2 h after the onset of ischemia. Moreover, enalapril significantly blunted the increases in circulating creatine kinase (CK) activity, as well as significantly prevented the loss in myocardial CK activity. These changes correlated with reduced myocardial loss of compounds containing free amino-nitrogen. Enalapril effectively acted as a converting enzyme inhibitor over the 5-hour course of the observation period. However, enalapril also acted as an angiotensin antagonist in isolated coronary arteries, a finding that may help explain its efficacy in myocardial ischemia. Enalapril did not appear to stabilize the membranes of cat liver lysosomes, and thus probably does not protect the ischemic myocardium by lysosomal stabilization.

Topics: Acute Disease; Angiotensin I; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Cats; Coronary Circulation; Coronary Disease; Creatine Kinase; Dipeptides; Electrocardiography; Enalapril; Male; Oligopeptides; Papillary Muscles; Teprotide

Enalapril, a novel angiotensin converting enzyme inhibitor, was given orally to 12 patients with chronic heart failure (NYHA functional class III and VI) and cardiomegaly. Heart rate, systemic arterial blood pressure, pulmonary arterial pressure, right and left ventricular filling pressures and cardiac index were monitored during dose efficacy titration. The optimal dose averaged 17 mg given once-daily. All patients were recatheterized three months later. After stabilization of cardiac filling pressures, all patients had left ventricular filling pressures in excess of 18 mmHg. Enalapril increased cardiac index acutely by 34% but at 12 weeks follow-up, cardiac index was not different from control levels. Left ventricular filling pressure was reduced acutely by 36% and by 41% at three months. Heart rate, systemic arterial and right atrial pressures and plasma concentrations of aldosterone were reduced during the observation period. Renin was markedly elevated. These changes were accompanied by marked and sustained clinical improvement and subjective well-being.

Topics: Aged; Blood Pressure; Coronary Disease; Enalapril; Female; Heart Failure; Heart Rate; Heart Ventricles; Hemodynamics; Humans; Male; Middle Aged