Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 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

The AIRE study--a trial involving over 2,000 patients with clinical heart failure after myocardial infarction--assessed different outcomes. The primary outcome was total mortality. The secondary outcome was time to death, or progression to severe/resistant heart failure, reinfarction or stroke. Tertiary analyses included hospitalization and mode of death. To obtain maximum quality in the validation of outcomes and to optimize the quality of the data in the study, an end-points committee reviewed all data following preset definitions prior to code break. All definitions used are reported here. Experience of the validation process demonstrated that there are wide variations in clinical practice and terminology not only among countries but also among individual investigators. Variation in the clinical handling and treatment of patients makes it imperative to validate outcomes centrally on the basis of available facts.
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PMID:Validation of primary and secondary outcomes and classification of mode of death among patients with clinical evidence of heart failure after a myocardial infarction: a report from the Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. 751 37

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

Prognosis of patients post-myocardial infarction depends largely on the degree of left ventricular dysfunction, which results from loss of contractile tissue and remodeling of infarcted and surviving myocardium. This remodeling process may result in chronically progressive dysfunction and ultimately in heart failure. Next to mechanical determinants humoral control of hypertrophy, dilatation and qualitative changes of surviving myocardium are discussed. A major determinant of the extent of remodeling is infarct size. Efficacy of angiotensin-converting enzyme (ACE) inhibitors on infarct size was tested in animal experiments with conflicting results. Recent clinical studies also report beneficial (GISSI-3 and ISIS-4) or no (CONSENSUS II) effects on survival post-myocardial infarction when ACE-inhibitors were used in the acute phase. Up to date it remains unsettled which patients may benefit from acute therapy with ACE-inhibitors. Three days after myocardial infarction hemodynamically stable patients with heart failure may be treated with ACE-inhibitors (AIRE study). Prognosis may be improved and manifestation of heart failure prevented or delayed also in patients without heart failure treated in this phase of myocardial infarction with ACE-inhibitors (SAVE study). Prevention of heart failure may also be observed in patients treated later (at least 4 weeks) after myocardial infarction (SOLVD prevention arm). It is essential for this indication that patients are carefully selected for treatment depending on left ventricular function. Duration of treatment in patients with severe left ventricular dysfunction probably has to be lifelong, the doses of ACE-inhibitors used have to be relatively high (e.g. 3 x 50 mg captopril or 2 x 10 mg enalapril).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Indications for ACE inhibitors in the postinfarct period]. 785 83

Angiotensin converting enzyme (ACE) inhibitors are effective across the whole spectrum of heart failure from mild to severe but there are little data on the use of ACE inhibitors specifically in patients with postinfarct heart failure. Pharmacological properties that might potentially be relevant to the choice of drug after myocardial infarction include differences in metabolism, possession of a sulphydryl group, tissue binding, duration of action, and side effect profile. Of these duration of action is probably the most important, as longer acting drugs generally cause more prolonged first-dose hypotension that shorter acting agents and first-dose hypotension is a particular concern in the early postinfarct period. In the SAVE study captopril was effective in reducing mortality and delaying the onset of symptomatic heart failure after myocardial infarction. Similarly, ramipril reduced mortality in the AIRE study. In contrast, enalapril was largely ineffective in CONSENSUS II. These differences result largely from study design and do not indicate an inherent superiority of captopril or ramipril over enalapril. Nonetheless, a short-acting agent should probably be used for the initial dose in postinfarct heart failure to minimize the risks of prolonged hypotension. This aside, the choice of agent is far less important than appropriate patient selection and appropriate maintenance dosages.
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PMID:Infarct-related heart failure: the choice of ACE inhibitor does not matter. 794 58

Recent studies have strengthened the arguments for the use of angiotensin-converting enzyme (ACE) inhibitors in the early postinfarct period. Those with clinically detectable heart failure, and hence at highest risk, will benefit most, as shown in the AIRE study, but those at lower risk with left ventricular dysfunction still have some benefit, theoretically through ventricular remodeling. In patients in the very early stages of acute myocardial infarction, three trials have shown discordant results. In CONSENSUS-II, intravenous enalaprilat followed by oral enalapril gave no benefit, rather causing excess hypotension and a possible increase in mortality. In ISIS-4 and GISSI-3, mortality improved by 0.46% and 0.8%, respectively, with risk reductions of 9% and 11%. Added transdermal nitrate in GISSI-3 gave a total reduction of 17%. In view of the risk of hypotension (20% in ISIS-4, compared with placebo 10%), very early ACE inhibition will probably only be used for selected patients. Logically, one target group would be those seen 7-24 hours after the onset of symptoms, particularly 7-12 hours, at which time captopril alone gave a reduction of 14.5% in risk. These mortality differences compare favorably with those recently found when comparing tPA and streptokinase in the GUSTO study.
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PMID:The new trials: AIRE, ISIS-4, and GISSI-3. Is the dossier on ACE inhibitors and myocardial infarction now complete? 794 63

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


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