Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment with angiotensin converting enzyme (ACE) inhibitors delays deterioration and improves survival in chronic congestive heart failure and left ventricular dysfunction. In two large placebo-controlled trials with survivors of acute myocardial infarction, but with left ventricular dysfunction, mortality was significantly lower in the ACE inhibitor arms, with risk reductions of 19% (with captopril) and 27% (with ramipril). A study of left ventricular dysfunction in more than 4000 patients resulted in significantly fewer myocardial infarctions among patients given enalapril than in those receiving placebo; the risk reduction was 24%. Knowledge of the degree of neurohormonal activation in patients with congestive heart failure (New York Heart Association [NYHA] Functional Class II-III) appears to be of major importance in determining the efficacy of ACE inhibition. Patients with plasma concentrations above normal show the greatest increase in survival when treated with ACE inhibitors compared to similarly treated patients with low or normal neurohormonal plasma levels as well as those treated with placebo or direct-acting vasodilators. In a study of 239 patients with NYHA Class IV heart failure, randomized to receive enalapril or placebo, mortality was significantly reduced in patients receiving enalapril who had plasma noradrenaline, adrenaline, angiotensin II, aldosterone, or atrial natriuretic peptide levels above median values. No significant differences in survival between groups were found in patients with hormone levels below the median. A study in 804 men with congestive heart failure who received either enalapril or hydralazine plus isosorbide dinitrate showed the greatest reduction in mortality after 2 years in enalapril treated patients with plasma noradrenaline levels > 900 pg.ml-1 or plasma renin levels > 16 ng.ml-1.h-1. These results indicate that the main rationale for ACE inhibition in chronic congestive heart failure, in left ventricular dysfunction, and after myocardial infarction is the modulation of prolonged neurohormonal activation. Knowledge of this effect may provide the means to forestall disease progression and thus offer long-term treatment benefits.
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PMID:Neurohormonal activation and congestive heart failure: today's experience with ACE inhibitors and rationale for their use. 868 64

Magnesium sulphate has antiarrhythmic and antithrombotic properties, a coronary and systemic vasodilating action, a direct myocardial protective effect in experimental and clinical models of ischemia-reperfusion injury. Two meta-analyses have pooled the results of several small studies that had analyzed the effect of controlled hypermagnesiemia in acute myocardial infarction before the advent of thrombolytic and antithrombotic therapies. The results have shown a more than 50% mortality reduction, with a minimum estimated benefit of about 30%, and a reduction in ventricular arrhythmias of about 50%. In LIMIT-2, a double-blind trial of 2,316 patients where magnesium was administered as a 8 mMol bolus followed by a 24-hour infusion of 65 mMol, a 24% reduction in mortality was observed. However, these data have not been confirmed in the more than 58,000 patients of the ISIS-4 trial. In this study magnesium, at the same dose of the LIMIT trial, did not reduce 5-week mortality, neither in the general population (7.64% versus 7.24% in control patients, p = n.s.) nor in specific subgroups. The results of ISIS-4 have excluded the routine use of magnesium sulphate in acute myocardial infarction in the era of fibrinolysis and aspirin, beta-blockers and ACE-inhibitors. Nevertheless, magnesium administration could still be considered in certain clinical situations, such as 1) the presence of contraindications to fibrinolysis and aspirin, 2) the treatment of ventricular tachyarrhythmias unresponsive (or as an alternative) to lidocaine, 3) severe hypertension when beta-blockers are not indicated.
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PMID:[Magnesium sulfate in acute myocardial infarction]. 868 39

The author describes the assessment of the effectiveness of antihypertensive drugs according to the T-P (Trough-Peak) ratio, i.e. the effect at the end of the dosage period to the effect during its peak after subtraction of the placebo effect. He draws attention to methodological difficulties which make it so far difficult to compare data from the literature. It is, however, advisable in clinical practice of the treatment of hypertension to assess the blood pressure at the end of the dosage period rather than during the peak of effectiveness, as frequently practiced. Drugs with a long biological half-life are particularly useful. The most important criterion of effectiveness of antihypertensives is, however, their effect on the cardiovascular and cerebrovascular mortality and morbidity. Only on diuretics and beta-blockers extensive data are available indicating that they lead to a decline of the morbidity and mortality. Therefore they should be the drugs of first choice, in particular in elderly hypertonics. Data on calcium channel blockers, in particular nifedipine are controversial. ACE inhibitors are suitable in heart failure, asymptomatic dysfunction after acute myocardial infarction and in type 1 diabetes mellitus. Only at present investigations are under way to assess whether the effect of new and more expensive antihypertensives on mortality and morbidity is greater than the effect of diuretics and beta-blockers and whether they will be suitable drugs of first choice.
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PMID:[Evaluation of the effectiveness of antihypertensive therapy. Is the trough-peak ratio the determining factor?]. 868 81

The rationale for using angiotensin converting enzyme (ACE) inhibitor therapy after acute myocardial infarction has been largely founded on observations made in experimental situations, and in humans before the routine introduction of reperfusion therapies. An important area of ongoing debate therefore continues to be the role of ACE inhibition as an early adjunct to attempts to achieve and maintain patency of infarct-related coronary arteries. Data from clinical trials indicate a substantial survival benefit in patients with impaired ventricular function, but provide little support for the routine treatment of the remaining majority of patients. An important issue in determining whether these agents should be used in a more general and long-term secondary prevention role, is their potential ability to prevent subsequent reinfarction. However, such a strategy is unlikely to be enhanced by either immediate initiation of treatment or withdrawal after just 1 month of therapy.
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PMID:Clinical background to the use of ACE inhibitor therapy after myocardial infarction. 874 66

Ischaemic heart disease is a major cause of chronic heart failure in Western societies. Despite some progress in the treatment of heart failure, it is still a disabling disorder with both high mortality and high morbidity. The incidence of chronic heart failure has increased over the past decade, probably as a result of the recent success in the management of patients with acute myocardial infarction. The importance of measures with potential capacity to prevent the development of symptomatic heart failure may be best illustrated by the fact that, among patients with left ventricular dysfunction, the prognosis is much worse in those with symptomatic failure than in those who are asymptomatic. Recently, the efficacy of angiotensin converting enzyme (ACE) inhibitors after myocardial infarction has been studied in a number of large placebo-controlled trials. These studies indicate that patients with symptomatic or asymptomatic left ventricular dysfunction after an acute myocardial infarction should receive long-term treatment with an ACE inhibitor and that such treatment may improve survival, reduce the incidence of overt heart failure and reduce the risk of reinfarction.
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PMID:Prevention of congestive heart failure by ACE inhibition in patients with acute myocardial infarction. 874 67

This review summarizes the evidence from five of the larger randomized controlled trials evaluating the effects of angiotensin converting enzyme inhibitors started in the early phase of myocardial infarction on subsequent mortality and major morbidity. Altogether, information on about 98,000 patients is available from these trials. In four studies, trial treatment was started within 24 h, and in one study within 36 h, of the onset of symptoms of acute myocardial infarction, and mortality was assessed after a few weeks or months of treatment. When taken together, these trials show that angiotensin converting enzyme inhibitors produce a significant 7% relative risk reduction in mortality (P < 0.006), which corresponds to an absolute difference of about five fewer deaths per 1,000 patients treated. The benefits may be greater in higher-risk patients (e.g. those with previous myocardial infarction, heart failure or large infarcts). These results demonstrate that for a wide range of patients without clear contraindications, angiotensin converting enzyme inhibitors started early in acute myocardial infarction prevent further deaths in the first few weeks when added to standard therapy (aspirin, thrombolytic therapy and beta-blockers). The early benefits seen with ACE inhibitors seems to persist for at least the first year. The clinical implications of these results are discussed.
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PMID:Effects of ACE inhibitors on mortality when started in the early phase of myocardial infarction: evidence from the larger randomized controlled trials. 874 69

Numerous large, double-blind, randomized trials have demonstrated that, overall, angiotensin converting enzyme (ACE) inhibition improves survival of patients after acute myocardial infarction (AMI). However, several practical issues concerning ACE inhibition in the presence of AMI have not yet been answered. These include whether ACE inhibition should be initiated in all patients with AMI, how soon ACE inhibition should be attempted in relation to onset of pain and possibly thrombolysis, and, lastly, how long ACE inhibition should be maintained after the acute event. Each of these issues is addressed, and recommendations are made on the basis of the results from recent randomized trials in AMI and congestive heart failure.
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PMID:Practical issues for the use of ACE inhibitors in acute myocardial infarction. 874 70

Left ventricular remodelling after acute myocardial infarction, through long-term left ventricular chamber dilatation and increased wall stress can result in alteration of the contractile properties of the non-infarct zone, impairment of the systolic and diastolic performances of the left ventricle, and eventually congestive heart failure. Left ventricular remodelling is influenced by several factors, among which the role of systemic and tissue renin angiotensin systems is determinant. Pharmacological interventions on the renin angiotensin systems were shown to limit left ventricular remodelling and reduce mortality from acute myocardial infarction in rats and humans, although the results of some trials remain controversial. To date, the beneficial effects of ACE inhibitors have only been demonstrated in patients with a low residual ejection fraction. Recent observations of changes in left ventricular chamber dilatation and left ventricular wall hypertrophy occurring over the course of time after acute myocardial infarction allow better definition of the subset of patients who are at risk of progressive left ventricular dysfunction and congestive heart failure. An akinetic surface >20%, a left ventricular ejection fraction <0 x 40, an anterior location of the infarction, a stroke volume <31 ml.m(-2) during the acute phase, and persistent occlusion of the infarct-related artery are the most powerful predictors of late left ventricular function impairment. Some issues remain controversial, such as the optimal time for introducing ACE inhibitors after the onset of symptoms, the potential additive effects of ACE inhibitors given in conjunction with thrombolytic therapy, and the role of systemic angioplasty of the infarct-related artery.
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PMID:Left ventricular remodelling after acute myocardial infarction--solved and unsolved issues. 882 58

Calcium antagonists are well accepted in the prevention of ischaemia in patients with chronic stable angina, unstable angina, variant angina, and silent ischaemia, and in the treatment of hypertension. Although all of these compounds increase myocardial oxygen supply by reducing coronary tone and decrease myocardial oxygen demand by reducing systolic pressure and myocardial contractility, the magnitude of these effects may differ from one agent to another. Some calcium antagonists, such as verapamil and diltiazem, reduce heart rate and attenuate heart rate increases in response to stress, while in contrast, dihydropyridine calcium antagonists such as nifedipine may cause reflex increases in heart rate. These differences may be of importance in light of epidemiologic evidence that lower heart rates are associated with a reduced long-term risk of cardiovascular mortality, and experimental data showing that a lower heart rate may protect against the development of atherosclerosis. Calcium antagonists also inhibit platelet aggregation and thrombus formation which may contribute to their anti-ischaemic effects. Clinical trial data suggest that calcium antagonists may stay the progression of atherosclerosis. Mechanisms underlying an anti-atherosclerotic effect may include attenuation of endothelial dysfunction, prevention of LDL, peroxidation, stimulation of LDL receptor activity, inhibition of superoxide radical generation, and inhibition of vascular smooth muscle cell growth. Heart-rate-controlling calcium antagonists, such as verapamil and diltiazem, may reduce reinfarction rates following acute myocardial infarction and thus may have a role in post-infarction patients who do not show evidence of heart failure. Their use in heart failure patients receiving an angiotension-converting enzyme inhibitor (ACE-I) is under investigation in several large trials. Because calcium antagonists have a mechanism of action different from ACE-I, the pairing of a heart-rate-controlling calcium antagonist with an ACE-I might be expected to offer additive cardioprotective and vascular protective effects.
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PMID:The role of calcium antagonists in ischaemic heart disease. 884 1

Activation of the renin-angiotensin system (RAS) has been implicated in the pathogenesis of acute myocardial infarction (AMI). Similarly, reduced fibrinolytic activity has been associated with an increased risk of AMI. Evidence is now accumulating that the RAS plays an important role in the regulation of fibrinolysis and that pharmacological interruption of the RAS exerts a positive effect on endogenous fibrinolytic balance. This relationship appears to provide a partial explanation for the newly recognized effect of angiotensin converting enzyme inhibitors in preventing AMI.
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PMID:Role of the fibrinolytic system in preventing myocardial infarction. 886 33


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