enalapril and Angina--Unstable

Therapeutic activation of the vascular NO/cGMP pathway is induced by a variety of stimuli/mediators including physical activity, supplementation with the precursor L-arginine and organic nitrates which generate NO in the vasculature. The necessity of an enzymatic reduction for NO generation from these drugs as well as differences in the activity of the NO/cGMP pathway within the vascular tree determine the unique hemodynamic changes elicited by organic nitrates. These changes include preferential venodilation, vessel-size specific arterial dilation and improvement of the aortic distensibility and Windkessel-function. Some animal experiments and clinical investigations suggest that nitrates may also be endowed with cardioprotective and/or vasoprotective effects. "Early entry" therapy with nitrates do not significantly improve survival in myocardial infarction but increases the beneficial effects of the ACE-inhibitor enalapril by 50%. Furthermore, nitrates have been shown to improve survival in heart failure, but prognostic effects in stable angina pectoris are unknown. Short-term experimental and clinical investigations suggest that nitrate tolerance induced by nitroglycerin is associated with toxic effects in the vasculature, but this is not true for pentaerythrityl tetranitrate and isosorbide mononitrate. The observed endothelial dysfunction induced by a continuous treatment with nitroglycerin may be an additional risk for patients who receive continuous nitroglycerin to treat conditions such as unstable angina and acute heart failure. In general, nitrates are remarkably safe drugs and are well tolerated. Appropriate clinical trials are needed to answer the question whether nitrates can do more than symptomatic relief in cardiovascular disease.

Topics: Angina, Unstable; Animals; Cardiovascular Diseases; Cyclic GMP; Enalapril; Endothelium, Vascular; Hemodynamics; Humans; Myocardial Infarction; Nitrates; Nitric Oxide; Nitroglycerin; Platelet Aggregation

To estimate the time course of changes in brachial artery (BA) functional parameters in patients with unstable angina (UA) treated with angiotensin-converting enzyme inhibitors.. After examination, 30 patients with Braunwald Classes IB and IIB UA were randomized to two groups to receive perindopril or enalapril as part of combination therapy (Group 1 and Group 2, respectively). The authors carried out BA duplex scanning with a reactive hyperemia test, calculated the values of its viscoelastic properties, and determined pulse wave velocity (PWV) at baseline and after 3 months.. The patients of both groups did not differ in BA functional parameters at baseline. Following 3 months, Group 1 showed a reduction in Young's (p = 0.046) and Peterson's (p = 0.049) modules, an increase in compliance (p = 0.016) and distensibility (p = 0.02) coefficients, and a decrease in PWV (p = 0.23). Estimation of endothelium-dependent vasodilation of BA revealed a significant increase in its diameter increment both at testing minutes 1 (p = 0.047) and 2 (p = 0.049). In Group 2, only did the distensibility coefficient change significantly (p = 0.041). After the reactive hyperemia test, there was a significant rise in BA diameter increment at minute 1 (p = 0.047) and no change in this indicator at minute 2.. After 3-month treatment, the viscoelastic properties of BA improved in all indicators in the patients taking perindopril as part of combination therapy. The use of enalapril improved only an arterial distensibility index. The BA endothelial function estimated by its diameter increment also displayed better changes in the patients receiving perindopril.

Topics: Aged; Angina, Unstable; Angiotensin-Converting Enzyme Inhibitors; Brachial Artery; Drug Therapy, Combination; Elasticity; Enalapril; Endothelium, Vascular; Female; Follow-Up Studies; Humans; Hyperemia; Male; Middle Aged; Perindopril; Time Factors; Vasodilation; Viscosity

Long-term oral treatment of patients with acute coronary syndromes and type 2 diabetes mellitus with beta-adrenoblockers and angiotensin-converting enzyme inhibitors is associated with positive, though ambiguous changes in the left-ventricular structure and function. These changes should be the reason for choosing optimal therapy ensuring better prognosis in this patient population.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angina, Unstable; Angiotensin-Converting Enzyme Inhibitors; Bisoprolol; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Enalapril; Female; Heart; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Prognosis

Elevated plasma neurohormonal levels are associated with increased mortality rates in patients with symptomatic heart failure. A previous Studies of Left Ventricular Dysfunction (SOLVD) trial suggested that neurohumoral activation precedes the development of symptoms as demonstrated by increased neurohormonal levels in patients with asymptomatic left ventricular dysfunction. However, the significance of this early neurohumoral activation is unclear. The goals of this study were to determine the prognostic significance of the plasma concentrations of plasma norepinephrine (PNE) and atrial natriuretic peptide (ANP) and the renin activity (PRA) in patients with asymptomatic left ventricular dysfunction.. PNE and PRA were measured before randomization in 514 patients with left ventricular ejection fractions < or = 35% who did not require treatment for congestive heart failure and were enrolled in the SOLVD Prevention Trial. Plasma ANP levels were measured in a subset of 241 patients owing to study design. Using the Cox proportional hazards model that included left ventricular ejection fraction, New York Heart Association functional class, age, sex, treatment assignment to placebo or enalapril, and cause of heart failure, we examined whether these neurohormones predicted all-cause mortality, cardiovascular mortality, hospitalization for heart failure, development of heart failure, or development of ischemic events (myocardial infarction or unstable angina). PNE was the strongest predictor of clinical events in this patient population. PNE levels above the median of 393 pg/mL were associated with a relative risk of 2.59 (P = .002) for all-cause mortality, 2.55 (P = .003) for cardiovascular mortality, 2.55 (P = .005) for hospitalization for heart failure, 1.88 (P = .002) for development of heart failure, 1.92 (P = .001) for ischemic events, and 2.59 (P = .005) for myocardial infarction. PNE remained the most powerful predictor for all-cause mortality and ischemic events when the analysis included only the patients with histories of ischemic left ventricular dysfunction. The increases in other neurohormonal levels were not useful in predicting the subsequent development of clinical events.. Increased PNE levels in patients with asymptomatic left ventricular dysfunction appear to predict all-cause and cardiovascular mortalities and development of clinical events related to the onset of heart failure or acute ischemic syndromes. Thus, measurement of PNE may be a possible early marker for assessment of disease progression in patients with left ventricular dysfunction, and modulating the release or effect of PNE may lead to improved prognosis and/or a reduction in morbidity.

Topics: Angina, Unstable; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Norepinephrine; Placebos; Predictive Value of Tests; Prognosis; Renin; Risk Factors; Survival Rate; Ventricular Dysfunction, Left

An association between raised renin levels and myocardial infarction has been reported. We studied the effects of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, on the development of myocardial infarction and unstable angina in 6797 patients with ejection fractions < or = 0.35 enrolled into the two Studies of Left Ventricular Dysfunction (SOLVD) trials. Patients were randomly assigned to placebo (n = 3401) or enalapril (n = 3396) at doses of 2.5-20 mg per day in two concurrent double-blind trials with the same protocol. Patients with heart failure entered the treatment trial (n = 2569) and those without heart failure entered the prevention trial (n = 4228). Follow-up averaged 40 months. In each trial there were significant reductions in the number of patients developing myocardial infarction (treatment trial: 158 placebo vs 127 enalapril, p < 0.02; prevention trial: 204 vs 161 p < 0.01) or unstable angina (240 vs 187 p < 0.001; 355 vs 312, p < 0.05). Combined, there were 362 placebo group patients with myocardial infarction compared with 288 in the enalapril group (risk reduction 23%, 95% CI 11-34%; p < 0.001). 595 placebo group patients developed unstable angina compared with 499 in the enalapril group (risk reduction 20%, 95% CI 9-29%, p < 0.001). There was also a reduction in cardiac deaths (711 placebo, 615 enalapril; p < 0.003), so that the reduction in the combined endpoint of deaths, myocardial infarction, and unstable angina was highly significant (20% risk reduction, 95% CI 14-26%; p < 0.0001). Enalapril treatment significantly reduced myocardial infarction, unstable angina, and cardiac mortality in patients with low ejection fractions.

Topics: Angina, Unstable; Blood Pressure; Death, Sudden, Cardiac; Enalapril; Female; Heart Failure; Humans; Incidence; Male; Myocardial Infarction; Prognosis; Prospective Studies; Risk Factors; Stroke Volume; Time Factors