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)

Angiotensin converting enzyme inhibitors are now widely used in the treatment of hypertension and heart failure. They are clearly as effective as other conventional antihypertensive agents in reducing blood pressure and combined with diuretics seem likely to transform current management of chronic heart failure. Myocardial infarction remains the major cause of death in patients with raised blood pressure and current studies should establish whether the attractive features of ACE inhibitors translate into reduction in the rate of infarction or its consequences. Similarly, whilst symptomatic benefit undoubtedly accrues from their use in heart failure it is less clear that they can prolong life particularly when used in the immediate setting of a myocardial infarction. Again a number of ongoing major trials are set to establish whether these drugs reduce death in patients with chronic heart failure (V-HeFT II, SOLVD) and in patients immediately after myocardial infarction (CONSENSUS II, SAVE,. AIRE, GISSI III and ISIS IV). The physician has a wide choice of ACE inhibitors with different pharmacological profiles for clinical use.
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PMID:Cardioprotection and ACE inhibitors. 130 64

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.
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PMID:Angiotensin-converting enzyme inhibitors post-myocardial infarction. 758 74

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.
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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.
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PMID:[ACE-inhibitors after infarction: current knowledge and future prospects]. 763 66

As in hypertension, the addition of a second active drug is believed to enhance treatment efficacy; however, the extent to which a combination of two low-dose drugs outperforms conventional monotherapy remains uncertain. Established treatments of angina comprises nitrates compounds, beta-blockers and calcium antagonists, which are often given in combination. Beta-blockers are major players in this field as they inhibit the tachycardia induced by nitrates and calcium antagonists; there is therefore a pathophysiological justification for their use in combination therapy, supported by repeated confirmation of positive clinical effect. The most widely chosen calcium antagonists are dihydropyridines; verapamil may impair conduction. However, it is not clear whether combination enhances the effects of the individual antianginal substances. Diuretics are for most clinicians the keystone treatment of heart failure; diuretics are often combined with other drugs, e.g. amiloride and spironolactone. The latter also have a beneficial effect on myocardial structure (myocardium/collagen ratio). ACE-inhibitors are of proven clinical efficacy, and, in addition, have a beneficial effect on survival. They combine well with diuretics: because the diuretic stimulates renin release, the ACE-inhibitor can be given at a lower dose (enhancement of effect). There are, however, certain drawbacks (hypotension, hyperkalemia with antialdosterones). The results of combining ACE-inhibitors with calcium antagonists and beta-blockers await investigation. The ISIS studies demonstrated the advantages of combining beta-blockers, thrombolysis and aspirin in acute infarction. ACE-inhibitors have recently been added to the regimen with a positive effect (extended survival), especially in the presence of a decreased ejection fraction (SAVE, AIRE, GISSI 3 and ISIS 4 studies).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Combination therapy in cardiovascular diseases other than hypertension]. 767 73

Potential benefit or harm of drug therapy in patients with chronic congestive heart failure and those later presenting to hospital after an acute myocardial infarction (AMI) have been studied in a number of large-scale survival studies during the last few decades. Currently available data are reviewed in order to consider both methodology and also the clinical relevance of findings with emphasis on trials with ACE-inhibitors like CONSENSUS-II, the ISIS-4, GISSI-3 and Chinese mega-trials, TRACE, SAVE and AIRE. Results of SAVE and AIRE show a clear survival benefit for the patients. Furthermore, the benefit of both trials was in addition to any other benefit which resulted from aspirin, thrombolytic and beta-blocker therapies. In absolute terms, treatment of 1,000 patients with ramipril (AIRE) for 1 year would be expected to result in the prevention/delay of 40 premature deaths. The beneficial effects of ramipril were clearly apparent by 30 days though additional benefit beyond this point was also present. Furthermore, prespecified subgroup analysis revealed significant benefit for patients at risk like women and the elderly. A selective approach is argued for the treatment of patients with ACE-inhibitors after myocardial infarction.
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PMID:ACE-inhibitor therapy after myocardial infarction--a new treatment strategy. 785 81

First, we had the discussion 'Are all ACE inhibitors equal?', and the debate was really in relation to heart failure. I came away with the impression that although there might be variations with renal function, hypotension and so on, most of you felt that it was ACE inhibition that was of primary importance, and that it was therefore permissible to extrapolate from one study to another. The recently published AIRE study of post-infarct patients used ramipril, with a change in mortality that gives credence to the idea that it's not just captopril, not just enalapril, but is likely to be a class effect of ACE inhibitors. I think that's the feeling I got from you. Do ACE inhibitors prolong life? I think Professor Weich made a very simple and a very good point, because it allowed us a general extrapolation. The simple point is: the sicker the patient, certainly with heart failure, the more the benefit of the ACE inhibitor. It's like the idea that in elderly hypertensives, or the diabetic hypertensive, the greater the risk factor the greater the benefit. The more we want to treat prophylactically, whether it's micro-albuminuria, or transient hypertension, or minimal left ventricular dysfunction, the longer we will have to treat, and the more patients we will have to treat to get objective evidence of any differences. Professor Oosthuizen suggested that we should also be thinking of renal impairment, potential renal impairment with cardiovascular disease in diabetes as another valid end-point.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The Grande Roche ACE debate. 804 78

Unlike most cell-types in the body, cardiomyocytes do not replicate in adult life. Consequently myocardial infarction produces irreparable damage to the heart which in turn increases the likelihood of premature death. Recent trials indicate that immediate aspirin and thrombolytic therapy beneficially modify the natural history of myocardial infarction, reducing both short- and long-term mortality rates. However, the occurrence of early heart failure in as many as one third of patients continues to carry with it a particularly poor prognosis. Recent trials with ACE inhibitors indicate that delayed initiation (beyond 24 h) and long-term maintenance treatment of patients selected on the basis of either heart failure (AIRE Study) or an ejection fraction of less than 40% (SAVE Study) result in large reductions in all-cause mortality. Although the exact mechanism of this benefit remains uncertain the reduction of further myocyte death due to reinfarction or gradual toxic attrition has been suggested. The currently unreported ISIS-4 and GISSI-3 should provide additional information as to whether the clinical indications for ACE-inhibitor therapy should be extended to other patient groups.
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PMID:ACE inhibition, atherosclerosis and myocardial infarction--the AIRE Study in practice. Acute Infarction Ramipril Efficacy Study. 807 59

Up to September, 1993, several questions were open on the use of angiotensin converting enzyme (ACE) inhibitors after myocardial infarction. The SAVE trial has shown that patients with left ventricular dysfunction and a recent (mean 11 days) myocardial infarction benefit from assuming captopril per os during the subsequent clinical course. The SOLVD trials have indicated that therapy with enalapril per os increases the survival of patients with left ventricular dysfunction, a history of myocardial infarction and hemodynamic decompensation. However, the CONSENSUS II trial has not shown similar results on patients with all range left ventricular function, treated within 24 hours of infarction with i.v. enalaprilat and then enalapril per os. In this study, 6-month mortality has been slightly better in the placebo group, and there seems not to be any subgroup benefitting from the ACE inhibitor. In October and November, 1993, the International Cardiologic Community has received the results of 3 large multicenter trials on postinfarction patients: the AIRE (ramipril per os), the GISSI 3 (lisinopril per os) and the ISIS 4 (captopril per os) studies. These trials has pointed out the followings: 1) prompt therapy (within 24 hours of chest pain) with ACE inhibitors is able to improve short term survival in patients with clinical evidence of heart failure, in women and old patients; 2) ACE inhibitors and nitro derivatives are complementary therapies in the acute and subacute phase of infarction, and their association produces the best improvement in short-term survival. There seems to be no intelligible reason, up to now, to deem that any ACE inhibitor should be considered better than another one in the acute phase of infarction, but still during the first 72 hours after the onset of chest pain the advantages have been shown only with lisinopril and captopril. The negative results of the CONSENSUS II trial are probably dependent on the excessively abrupt acute hypotensive effect of i.v. enalaprilat. This last "large trial" decade has taught us that many treatments can be advantageous for acute myocardial infarction but, apart from thrombolysis, all other medical therapies should not be given extensively, but to peculiar patients carefully selected on clinical grounds. Guidelines from official consensus conferences are expected now, to segregate different patterns of clinical presentations to be treated differently.
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PMID:[Angiotensin converting enzyme inhibitors during acute phase of myocardial infarct]. 820 Apr 99

The increased mortality after myocardial infarction is related to the risk of reinfarction, sudden death, and the development and progression of heart failure; in congestive heart failure it is due to the progression of heart failure and sudden death. ACE inhibitors have been proven to prevent cardiovascular events, especially the progression of heart failure, in postinfarct patients with reduced ejection fraction and heart failure in the SAVE and AIRE trials. In patients with congestive heart failure, ACE inhibitor treatment has prevented cardiovascular death and reduced morbidity due to progressive heart failure in the SOLVD trials. In post-myocardial infarction patients, the calcium antagonist nifedipine did not affect mortality or morbidity; diltiazem improved prognosis in patients without congestive heart failure and in patients with non-Q-wave infarction; and verapamil improved prognosis by prevention of reinfarction and sudden death. Combination treatment with both verapamil, which has pronounced antiischemic properties and prevents sudden death and reinfarction, and an ACE inhibitor, which prevents the progression of heart failure, is a possibility for future cardiovascular therapy that should be evaluated.
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PMID:ACE inhibitors and calcium antagonists in the treatment of congestive heart failure. 856 67


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