Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Results from SOLVD, SAVE, AIRE, GISSI-III, ISIS-IV, and the Chinese Captopril Trial suggest that therapy with ACE inhibitors, at least with enalapril, captopril, ramipril, and lisinopril, induce significant reduction in morbidity and mortality rates in patients with ischemic heart disease, myocardial infarction, and a wide range of ventricular function and myocardial infarction. SOLVD and SAVE results, in particular, demonstrate improved survival and reduced major ischemic events in patients with depressed systolic ventricular function. SOLVD points out that institution of ACE inhibitor therapy need not be done immediately post-myocardial infarction to accrue benefit. GISSI-III and ISIS-IV, on the other hand, suggest that use of ACE inhibitor drugs early post-myocardial infarction produces significant, albeit small, benefits when drugs are begun early post-event in conjunction with other routinely used therapeutic strategies. The prospective, well-designed, and well-controlled nature of these clinical trials, the consistency of their findings, and the high level of morbidity and mortality in placebo groups establish the importance of preventing ischemic events with the prescribed ACE inhibitors. Particularly important is the fact that none of these clinical trials were designed to determine optimal dose or frequency of administration of the ACE inhibitors chosen. Targeting dose principles were utilized and clinicians wishing to generate similar results in their own patient population should choose one of the ACE inhibitors studied and administer it in the manner described in hopes of achieving outcomes similar to those detailed in the summarized clinical trials. Finally, recommendations regarding post-myocardial infarction therapy with ACE inhibitors can be summarized. Patients having acute or remote infarction should have an assessment of ventricular function. All patients with depressed systolic function, whether they are or are not symptomatic, should receive a trial of an appropriate ACE inhibitor. Patients suffering an acute myocardial infarction should have an assessment of ventricular function early and, if the ejection fraction is low (probably < 50%), an appropriately chosen ACE inhibitor should be begun after 24 hours have elapsed. ACE inhibitor therapy should be begun in combination with other proven effective post-myocardial infarction treatment strategies. In patients with normal systolic function, advantages of ACE inhibitor therapy are less clear, but patients with large anterior wall myocardial infarction will likely benefit, even without objective evidence of left ventricular systolic dysfunction. Concomitant utilization of thrombolytic agents, aspirin, and beta blockers should not interdict use of ACE inhibitor therapy.
 ...
PMID:Angiotensin-converting enzyme inhibitors post-myocardial infarction. 758 74

Neurohormonal activation may provide a pathophysiological link between acute myocardial infarction and chronic congestive heart failure, and modulation of neurohormonal activity may be an important therapeutic target in these conditions. Plasma neurohormones were studied in 55 patients with acute myocardial infarction. Angiotensin II, noradrenaline and ANP were elevated in the early phase but tended to normalize during the first week in patients without signs of heart failure. In patients with heart failure angiotensin II and noradrenaline remained elevated for 1 month and ANP for 4-6 months. During head-up tilt, angiotensin II and noradrenaline increased most in patients with heart failure. In patients with a first myocardial infarction there was a positive correlation between sustained neurohormonal activity and infarct size. Almost complete suppression of plasma ACE activity was achieved within 30 min in 48 patients treated with intravenous enalaprilat, initiated within 24 h from the onset of infarction. The drug was tolerated in dosages of 1.0-1.2 mg given over 1-2h. Patients with systolic blood pressure between 100 and 110 mmHg incurred a greater risk of hypotension than those with higher blood pressure at baseline. Tolerance was not worse among patients treated with intravenous diuretics, metoprolol or nitroglycerin. A total of 98 patients were randomized to treatment with enalapril or placebo, initiated within 24 h from onset of infarction and continued for 4-6 months. During treatment there were no significant differences in plasma levels of angiotensin II, aldosterone, ANP or catecholamines between groups. Echocardiographic recordings were performed in 28 patients. Among patients on placebo there was a positive correlation between plasma levels of noradrenaline at days 5-7 and the increase in left ventricular volumes during the study period, and an inverse correlation between plasma aldosterone at days 5-7 and the increase in left ventricular ejection fraction during the study. No such correlation was found among patients on enalapril. ANP levels at 1 month correlated inversely with the left ventricular ejection fraction at the same time. Plasma neurohormones were measured in 223 patients with mild or moderately severe chronic heart failure, randomized to treatment with ramipril or placebo for 3 months. There was wide variation in hormone levels. Noradrenaline and aldosterone correlated inversely with exercise duration at baseline. Noradrenaline correlated positively with the degree of symptoms. Aldosterone and ANP were reduced with ramipril compared with placebo. Noradrenaline was reduced among patients with baseline levels in the highest tertile. Plasma hormones were also measured at peak exercise in 54 patients. Hormonal levels at rest correlated strongly with those at peak exercise.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Neurohormonal activation in patients with acute myocardial infarction or chronic congestive heart failure. With special reference to treatment with angiotensin converting enzyme inhibitors. 759 49

On the basis of the development of therapeutical procedures in acute myocardial infarction (AIM) the author offers the current standpoint to the standard medicamentous therapy of this disease. As AIM is caused by thrombotic occlusion of the coronary artery, the main therapeutical position is ascribed to the thrombolytic therapy. An important position is ascribed to acetylsalicylic acid and betablockers. The optimal application is intravenous administration at an early stage of the disease. The ISIS-4 study displayed a beneficial impact on mortality including ACE inhibitors. The symptomatic therapy includes analgetics administered at an early stage of the disease, nitrates and magnesium. Antiarrhythmics are not to be applied in a routine pattern. Cardiogenic shock can be treated exclusively by invasive therapeutical intervention (e.g. direct PTCA or emergent bypass).
 ...
PMID:[Treatment of acute myocardial infarct]. 763 20

In acute myocardial infarction, the results of the trials with ACE-inhibitors have not been always good, in contrast with what has been observed in chronic heart failure. The comparison of these compounds with the placebo has demonstrated lack of reduction of mortality in the study CONSENSUS II, favorable results on the survival as first endpoint and on the secondary endpoints, as reinfarction, heart failure and stroke in the studies SOLVD, AIRE, GISSI 3, ISIS 4, and uncertain (interim report) results in the Chinese study. Nevertheless, the analysis of the recruitment of the patients with acute infarction and the way these patients have been treated seem to be the most important cause of the conflicting results. ACE-inhibitors have proved no efficacy in acute myocardial infarction without signs of left ventricular failure (CONSENSUS II), have worsened the clinical picture and the mortality in patients in shock or with severe heart failure in the acute phase. On the reverse, in presence of mild to moderate left ventricular dysfunction and failure, the use of ACE-inhibitors has been followed by reduction of mortality in the early (AIRE, GISSI 3, ISIS 4), medium term (GISSI 3) and long-term follow-up (up to 4 years in the AIRE study). In parallel with the reduction of the primary endpoint, also secondary endpoints have been favorably influenced by the different ACE-inhibitors. No differences have been observed among the different class of compounds. ACE-inhibitors seem, therefore, to have a clear indication in acute myocardial infarction with mild or moderate signs and symptoms of heart failure.
 ...
PMID:[Trials with ACE-inhibitors in acute myocardial infarction]. 763 58

Experimental and clinical findings showing a beneficial effect on ventricular remodelling have led to a widespread use of ACE-inhibitors in myocardial infarction. Recent trials (SAVE, AIRE, GISSI 3, ISIS 4) have clearly demonstrated that in patients with left ventricular dysfunction and/or heart failure the treatment with ACE-inhibitors is mandatory, although several questions remain unanswered. Recent experimental observations on the relationship between ACE and endothelial function, and between ACE and intimal proliferation have gone forward leading to new perspectives on the potential use of ACE-inhibitors in all patients with acute myocardial infarction.
 ...
PMID:[ACE-inhibitors after infarction: current knowledge and future prospects]. 763 66

A number of small, randomised clinical trials and one large trial of intravenous magnesium have been conducted on patients with acute myocardial infarction (AMI). Most of these trials indicate that treatment with magnesium has a beneficial effect on short term mortality, although in most of the small trials the results are inconclusive. A systematic overview of mortality and serious morbidity data from all the available randomised controlled trials of magnesium conducted in a total of nearly 4000 patients with AMI indicates that there were 123 deaths in 1974 patients allocated magnesium, and 193 deaths in 1949 controls (odds ratio 0.61, 95% confidence interval 0.48 to 0.76, p < 0.0001). Data on the effects of magnesium on serious ventricular arrhythmias and heart failure are incomplete, and definitions for these serious complications of AMI vary greatly among the trials. Nevertheless, the available data suggest that magnesium also significantly reduces these 2 serious forms of morbidity. These data suggest that magnesium given to patients during AMI can produce significant reductions in mortality and serious morbidity. Although the mechanism of action of magnesium is likely to be independent of other currently used agents, its value when added to thrombolytic therapy, beta-blockers, angiotensin converting enzyme (ACE) inhibitors and nitrates is not clear, and is presently being studied in the very large Fourth International Studies of Infarct Survival (ISIS-4) trial.
 ...
PMID:Role of magnesium in reducing mortality in acute myocardial infarction. A review of the evidence. 769 27

The aim of our study was to examine if echocardiography can reproducibly be used in a multicentre study to select high risk patients with reduced left ventricular function early after an acute myocardial infarction (MI). In the TRAndolapril Cardiac Evaluation Study (TRACE) patients with reduced left ventricular systolic function were randomized 3-7 days post MI to receive either the ACE inhibitor trandolapril, or placebo. Twenty-seven Danish centres participated and 7001 consecutive MI patients were screened for entry. Local doctors and technicians who had received a brief but thorough training course recorded a two-dimensional echocardiographic examination on videotape 2-6 days after MI. Within 24 h, wall motion index (WMI) was visually assessed by one of two cardiologists (examiners) with considerable experience in echocardiography. A WMI of < or = 1.2 (corresponding to a left ventricular ejection fraction (LVEF) < or = 0.35) meant that the patient was eligible for randomization in the TRACE study. Two other experienced cardiologists with substantial experience in echocardiography (controllers) performed blind reassessment of 155 randomly chosen videotapes. We showed that 93% of the 7001 screened MIs had an assessable echocardiogram. WMI was < or = 1.2 in 37% of patients. The one-year mortality was inversely related to WMI, being 60%, 30%, 14% and 11% in patients with a WMI < 0.8, 0.8-1.2, 1.3-1.6 and > 1.6, respectively. In the random sample of 155 videorecordings that were reevaluated, 97% were found to be technically adequate for analysis both by the examiners and the controllers.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:An echocardiographic method for selecting high risk patients shortly after acute myocardial infarction, for inclusion in multi-centre studies (as used in the TRACE study). TRAndolapril Cardiac Evaluation. 769 30

Successful management of acute myocardial infarction depends in the first instance on the patient recognising the symptoms and seeking help as quickly as possible. Once in hospital, fast track admission procedures and protocols for pain relief, early thrombolysis and appropriate ancillary measures (eg aspirin, i.v. betablockers) should be promptly instituted. Specialist advice and, if necessary, transfer to specialist unit should be considered if additional complications arise. Follow-up management after discharge from hospital requires cooperation between primary and secondary care to prolong survival by reducing risk factors, using aspirin, betablockers and angiotensin converting enzyme inhibitors and instituting a suitable rehabilitation programme. Audit measures are included in the report to help general practitioners and hospital doctors review their practice and assess it against the standards set.
 ...
PMID:The management of acute myocardial infarction: guidelines and audit standards. Report of a workshop of the Joint Audit Committee of the British Cardiac Society and the Royal College of Physicians. 788 23

Ramipril is a second generation angiotensin converting enzyme (ACE) inhibitor. Like enalapril, it is a prodrug and is hydrolysed in vivo to release the active metabolite, ramiprilat, which has a long elimination half-life, permitting once-daily administration. The antihypertensive efficacy of ramipril has been confirmed in large-scale noncomparative studies conducted in general practice as well as in more rigorously controlled clinical trials. In the former, approximately 85% of patients with mild to moderate essential hypertension have responded successfully to treatment with ramipril 2.5 or 5 mg/day, while comparative trials indicate that the antihypertensive efficacy of the drug is equivalent to that of other established ACE inhibitors and the beta-adrenoceptor antagonist atenolol. As expected, the response rate to ramipril monotherapy is lower in patients with severe hypertension (around 40%), although the blood pressure lowering effect can be enhanced with the addition of a diuretic such as hydrochlorothiazide or piretanide. The antihypertensive efficacy of ramipril is maintained in patients with diabetes mellitus and preliminary data indicate that the drug has the beneficial effect of decreasing urinary albumin excretion in diabetic patients with nephropathy. Ramipril is superior to atenolol in causing regression of left ventricular hypertrophy, although the clinical significance of this effect per se remains to be established. The large-scale Acute Infarction Ramipril Efficacy (AIRE) study demonstrated that ramipril 5 or 10 mg/day significantly decreased the risk of all-cause mortality by 27% in patients with clinical evidence of heart failure after acute myocardial infarction, even if transient. The beneficial effect of ramipril was apparent by 30 days of treatment and appeared to be greatest in patients with more severe ventricular damage after infarction. Ramipril is well tolerated in general practice, with 5% or fewer patients discontinuing therapy because of drug intolerance. The data available suggest that ramipril shares a similar tolerability profile to that of other established ACE inhibitors. Thus, clinical data confirm ramipril as a useful alternative ACE inhibitor for the treatment of patients with mild to moderate hypertension, and indicate a beneficial effect of the drug in patients with clinical evidence of heart failure after acute myocardial infarction. It is also reasonable to assume that ramipril will be of value in the treatment of patients with more established heart failure or asymptomatic left ventricular dysfunction.
 ...
PMID:Ramipril. An updated review of its therapeutic use in essential hypertension and heart failure. 777 15

When treating cardiovascular disorders such as arterial hypertension, the major goal of treatment is to reduce morbidity and mortality. The present review will concentrate on how the treatment of cardiovascular disorders affects mortality. Hypertension studies performed in the 1950s showed that treatment of malignant hypertension improved five year survival dramatically. More recent studies in patients with nonmalignant hypertension have shown positive effects on mortality as well, especially with regard to the treatment of hypertension in the elderly. Other cardiovascular disorders have also been treated successfully with regard to mortality. This is true in particular of postmyocardial infarction patients, in whom beta-blocker treatment has been effective. Moreover, patients with congestive heart failure have been shown to benefit from treatment with angiotensin converting enzyme (ACE) inhibitors as regards total mortality. The most recent addition to our knowledge stems from the GISSI-3 trials in which lisinopril, alone or in combination with nitrates, was shown to reduce mortality in patients with acute myocardial infarction.
 ...
PMID:Mortality matters. 780 12


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>