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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The ideal therapy for patients with chronic heart failure should reduce symptoms related to pulmonary congestion or low perfusion, prevent the progression of left ventricular dysfunction and, ultimately, should reduce mortality. Extensive studies in humans have investigated the effects of angiotensin-converting enzyme (ACE) inhibitors on these goals of therapy. As an example, the ACE inhibitor cilazapril significantly improved exercise tolerance, as borne out by a meta-analysis of six placebo-controlled, randomized 3-month trials. Comparison of the effects of cilazapril and captopril vs. placebo in one of the trials documented similar improvement in exercise tolerance (14 vs. 17%). Results from other randomized comparative trials suggest that the improvement in symptoms represents a class effect of ACE inhibitors. A beneficial effect of ACE inhibition on the progression of left ventricular dysfunction has also been demonstrated in the SOLVD trial, and a reduction of mortality has been amply documented in several mortality trials (CONSENSUS I, SOLVD, V-HeFT-II, SAVE, AIRE, SMILE) in patients with or without preceding myocardial infarction. Reports that ACE inhibitors also reduce the incidence of reinfarction after myocardial infarction have not been confirmed in all studies but raise the interesting concept that ACE inhibition may interact, in a beneficial but thus far not well-understood way, with key processes in the development of atherosclerosis, thereby preventing plaque rupture, thrombus formation, and myocardial infarction. Taken together, a large database convincingly demonstrates that ACE inhibitors are effective not only in improving symptoms but also in the prevention of progression of left ventricular dysfunction, in the reduction of mortality, and possibly in stabilizing the atherosclerotic disease process.
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PMID:Clinical benefit of angiotensin-converting enzyme inhibitors in chronic heart failure. 872 95

A series of elegant experimental studies and careful clinical observation over a decade or more have led to the concept of 'infarct expansion' and 'remodelling' of the heart, culminating in a number of major mortality studies indicating the effectiveness of angiotensin-converting enzyme (ACE) inhibitors in patients after myocardial infarction (MI). But has this concept been too narrow in predicting which patients might benefit from treatment with ACE inhibitors? Measurable infarct-expansion with progressive dilatation probably occurs in less than 20% of patients, whereas increase in volume and hypertrophy of the heart as responses to compromised function are likely wherever significant myocardial damage has occurred. Irrespective of infarct expansion, cumulative extensive damage can lead to an inevitable downward spiral with gross ventricular dilatation and death in heart failure. But in the majority of patients after MI a 'new equilibrium' is established in which initial dilatation and subsequently hypertrophy restore adequate function. Is it possible to distinguish patients in whom the cost and inconvenience of long-term therapy with an ACE inhibitor justify the likely benefit from treatment after an MI? The SAVE, AIRE and recent TRACE studies allow a rational approach for the clinician, indicating the effectiveness of these drugs in patients with evidence of impaired ventricular function. However, the prospect that ACE inhibitors prescribed long term might also prevent myocardial reinfarction could justify wider use. Post-MI patients are an easily identifiable high-risk group for a cost-effective programme of secondary prevention. Reinfarction in an already damaged ventricle carries a particularly poor prognosis and its prevention by ACE inhibitors could make a major contribution to the undoubted benefit from these agents. The recently completed TRACE study with its long-term follow-up may help resolve this issue, which is also being investigated in a number of long-term prospective studies in populations at high risk of cardiovascular disease.
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PMID:What have the ACE-inhibitor trials in postmyocardial patients with left ventricular dysfunction taught us? 883 30

The proportion of patients reported to die suddenly or from progressive circulatory failure is not consistent among studies of heart failure. Lack of an adequate or consistent classification of how patients die contributes to the current confusion over the mode of death in heart failure. Defining how patients with heart failure die could be important in developing strategies to reduce the continuing high mortality associated with this condition. We identified 27 studies that reported 50 or more deaths among patients with heart failure to ascertain how death was classified. Definitions of sudden death appeared heterogeneous and the majority of studies failed to publish or make reference to how circulatory failure was defined. A framework for the classification of the mode of death has been developed in which clear separation of the activity and place at the time of death, cause of death, mode of death, and events prior to death is made (ACME: Activity, Cause, Mode and Event). This mode of classifying death has been successfully piloted in two mortality studies; AIRE and NETWORK. Classifying mortality in this way will help identify pathways leading to death and hence suggest therapies and strategies to reduce mortality in patients with heart failure, a group of patients whose prognosis remains poor.
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PMID:Mode of death in chronic heart failure. A request and proposition for more accurate classification. 888 25

Doctors treat patients, not populations. 'Evidence-based' practice is essential but extrapolation to the individual patient is always necessary and this fact is well illustrated by data from trials of ACE inhibitors post-myocardial infarction. In the AIRE (Acute Infarction Ramipril Efficacy) study, 2,006 patients with some evidence of heart failure, even if transient, after a myocardial infarction, were randomised to receive oral ramipril or placebo in addition to standard treatment. Follow-up was for a minimum of six and an average of 15 months. The risk reduction in total mortality was 27% (95% CI 11-40%; p = 0.002); approximately 40 lives might be expected to be saved for every 1000 patients treated for one year. Benefit was apparent within weeks of starting treatment. Additional data from the AIRE study are considered in relation to the findings of other mortality trials. It is argued that ACE inhibitors offer most to those patients with impaired left ventricular function through a mechanism not related to the prevention of myocardial re-infarction.
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PMID:How ACE inhibitors reduce death from myocardial infarction: hypotheses from the AIRE study. Acute Infarction Ramipril Efficacy study. 899

It is now clear that angiotensin-converting enzyme (ACE) inhibitor treatment after myocardial infarction (MI) reduces mortality and morbidity. However, the benefits of ACE inhibition are not homogeneous and are largely confined to high-risk patients who have subjective or objective evidence of left ventricular (LV) dysfunction. How long treatment should continue is a vexed question, which also arises with other agents, for example beta-blocker use after MI. The AIREX study assessed the long-term magnitude and duration of the survival benefits observed with ramipril in patients after MI who have clinically defined heart failure. The mortality status of all 603 patients recruited from the UK centres involved in the AIRE study was verified at an extended 5-year follow-up (3 years after the AIRE study closed). Ramipril assignation was associated with a 36% relative and a 11% absolute mortality risk reduction. These findings strongly support the view to select patients on the basis of impaired LV function and reinforce the previously reported conclusions of the "selective" ACE inhibition post-MI trials. Using this approach, the survival benefit is not only of large magnitude but also sustained over many years. These results also argue for life-long treatment with an ACE inhibitor, once a decision to treat an individual patient after MI has been made.
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PMID:Clinical implications for the Acute Infarction Ramipril Efficacy extension (AIREX) Study. 992 43

We examined clinical outcomes associated with non-randomised digoxin therapy in a postmyocardial infarction population with clinical heart failure (AIRE study). Our results raise concern about the safety of digoxin in this population.
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PMID:Safety concerns about digoxin after acute myocardial infarction. 1043 70

Hospital mortality from acute myocardial infarction has decreased in the last two decades. Left ventricular dysfunction therefore have been mainly due to ischemia. After extensive myocardial infarction, there are processes of adaptation (remodeling) which result in altered geometry of the left ventricle. The effects of this on neurohormonal systems (organ regulation), on the changed ratio of myocyte mass and collagen content owing to reactive and reparative fibrosis (organ texture) and on the molecular and cellular mechanisms (organ structure) are of crucial importance. Depending on the structural changes, the myocardial contractility decreases. This is associated with an activation of the circulating renin-angiotensin-aldosterone system (RAAS). The fundamental knowledge available has led to the therapeutic use of ACE inhibitors in the post-infarct period. This treatment enabled a sustained reduction of mortality in several large-scale randomized studies. The effect of early administration in patients with clinical signs of heart failure and/or left ventricular dysfunction was very much greater compared to unselected controls. Only 17 and 13 patients had to be treated after selection in order to save one life in the AIRE and TREACE Study respectively (NNT: number needed to treat), whereas e.g. in the ISIS-4 study 200 unselected patients had to be treated. In clinical practice, however, this life-saving therapy is only used in every second patient requiring treatment. With consideration of an individual form of treatment (anterior infarction, large infarct area, reinfarction, clinical signs of heart failure as well as arterial hypertension and diabetes mellitus), a greater acceptance of evidence-based guidelines is thus desirable. Treatment with a high dose may be expected to be of additional benefit.
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PMID:[Left ventricular remodeling: pathophysiological mechanisms and therapeutic recommendations]. 1065 89

Angiotensin-converting enzyme (ACE) inhibitors are now accepted as part of the routine management of patients with heart failure. Their use has been mandated in all the new major mortality trials to test the efficacy of beta-blockers in heart failure. Morbidity and mortality remain high in those with heart failure even with the benefits proven for both these groups of agents. In spite of the evidence for benefit of ACE inhibitors they are persistently used in lower doses in clinical practice than tested in the large-scale trials. This was so prevalent as to allow the conduct of a substantial study, the ATLAS trial, to compare high and low dose ACE inhibition. Its equivocal findings have allowed different interpretations. Clinical experience would suggest that starting with a low dose is appropriate but the dose should be titrated then without undue delay to the levels used in the trials wherever possible. The evidence for benefit with these drugs had been obtained largely in patients with impaired systolic function. However the AIRE study selected patients with clinical evidence of heart failure after myocardial infarction rather than with impaired systolic function. A substantial and long-term benefit was found from ACE inhibition. A cohort of patients had ventricular function assessed and as anticipated almost one half had preserved systolic function. Whilst the absolute benefit in lives saved was greater in the higher risk/low ejection fraction group, the relative risk reduction was not significantly different between those with preserved or impaired systolic function. The publication of the HOPE trial, although not a study of patients with heart failure, has clarified the situation considerably for those taking day to day care of patients. The HOPE study selected patients on the basis of high cardiovascular risk excluding those with known impaired systolic function. Although not an entry requirement for the study, ejection fraction was measured in a substantial majority and was above 40% indicating preservation of systolic function. The ACE inhibitor ramipril markedly reduced the combined end-point of cardiovascular death, stroke and myocardial infarction. Importantly there was a highly significant 20% risk reduction in the rate of myocardial infarction, a prospectively defined end-point, over the average four and a half year follow-up. Taken together with the retrospectively derived evidence from the heart failure trials there is now compelling evidence that the ACE inhibitors prevent myocardial infarction. The majority of patients with clinical heart failure have underlying ischaemic heart disease. Prevention of myocardial infarction and control of blood pressure are two key factors in the management of these patients irrespective of systolic ventricular function. The ACE inhibitors like the beta-blockers therefore have a pivotal role in their management. A challenge to current clinical trials is to determine whether these properties are shared to the same degree by the angiotensin antagonists or if even further gains in benefit can come from their combination. The neutral findings of the ELITE II study comparing the angiotensin antagonist, losartan, with the ACE inhibitor, captopril, have heightened interest in the on-going trials addressing these issues.
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PMID:ACE inhibitors in heart failure: an update. 1119 59


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