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)

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

Based on the foregoing data it is not unreasonable to hypothesize that restoration of flow in the infarct-related artery at a later date might decrease mortality. If that is the case, then a strong argument can be made for coronary angiography in patients surviving acute myocardial infarction. Of course, the ideal way to investigate this problem is to perform a large-scale prospective trial in which patients who have an occluded infarct-related artery are randomized to a revascularization procedure or continued on nonsurgical therapy. The specific management strategy for the patient with an occluded infarct-related artery after myocardial infarction depends on several features that the patient exhibits. For example, the presence or absence of LV dilatation, arrhythmias, recurrent ischemia, or clinical heart failure may dictate one form of therapy or another. There is no generic postinfarction patient with an infarct-related artery occlusion. Choices of drugs to use in these patients include the vasodilators, such as nitrates and ACE inhibitors, as well as aspirin and beta blockers. The use of calcium antagonists, chronic anticoagulants, and antiarrhythmics should have specific indications. Antithrombin agents are still experimental.
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PMID:Management of myocardial infarction patients with an occluded infarct-related artery. 791 May 40

Prognosis after acute myocardial infarction is strongly associated with left ventricular dysfunction. However, asynergy does not necessarily imply loss of viability and myocardial necrosis. In fact, two different patterns of contractile dysfunction, possibly coexisting, have been shown after acute myocardial infarction: Stunning and hibernation represent distinct patterns of contractile dysfunction that share the character of reversibility. It is noteworthy, then, to identify the presence of these two conditions at the bedside and to develop medical treatment to effect recovery of myocardial dysfunction. This strategy has the potential to ameliorate the outcome of patients after acute myocardial infarction by improving left ventricular function. Beta-blocker therapy significantly reduces mortality and the incidence of reinfarction after an acute myocardial infarction: These benefits result from the prevention of sudden death, the reduction of the extent of myocardial injury during the acute phase, and a further antiischemic action. Nevertheless, beta-blocker therapy increases left ventricular dilatation. Recent experimental and clinical data show that ACE inhibitors confer positive therapeutic effects after myocardial infarction by reducing the extent of left ventricular dilation, by reducing mortality, and by improving the clinical outcome. Not all patients, however, can be subjected to this therapeutical approach because of the possible detrimental effects produced by hypotension and by block of neurohormonal activation, sometimes truly compensatory in the early phase. Therefore, it would be interesting to suggest a combination therapy of a beta-blocker with a vasodilator agent (ACE inhibitor or calcium-channel blocker.
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PMID:Left ventricular function and prognosis after myocardial infarction: rationale for therapeutic strategies. 794 74

In this study, the acute haemodynamic effects of angiotensin converting enzyme (ACE) inhibition with intravenous enalaprilat alone or in combination with preload restoration were determined in patients with severe heart failure complicating acute myocardial infarction. Ten patients with raised pulmonary arterial wedge pressure (PAWP > or = 18 mmHg) were first studied during constant conventional vasodilation with diuretic and inotropic medication, by monitoring central haemodynamics and arterial blood gases. The same variables were measured before enalaprilat infusion, after preload reduction with enalaprilat (1 mg.h-1, rate doubled every 30 min until PAWP decreased > or = 25% or up to total cumulative dose of 10 mg) and after preload restoration with fluid loading (4% albumin given 15 ml.min-1 to restore PAWP to baseline) during continuous low dose enalaprilat infusion. Enalaprilat alone (median dose 0.9 mg) reduced significantly the PAWP (from 25 to 17 mmHg; P = 0.004), the mean arterial pressure (from 87 to 83 mmHg; P = 0.008), the mean pulmonary arterial pressure and the right atrial pressure. The cardiac index, stroke volume index and systemic vascular resistance index remained unchanged. Preload restoration during continuous enalaprilat infusion (median dose of 4% albumin 230 ml, and enalaprilat 0.2 mg) did not further enhance left ventricular function; rather, there was a nearly significant decrease in myocardial perfusion pressure. Arterial oxygenation remained unchanged throughout the study. In conclusion, adding intravenous enalaprilat to conventional therapy makes it possible to relieve pulmonary congestion while maintaining the cardiac function and arterial oxygenation. Preload restoration during continuous ACE inhibition offers no further advantages, and may have adverse effects, since the myocardial perfusion pressure may fall.
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PMID:Haemodynamic effects of enalaprilat and preload in acute severe heart failure complicating myocardial infarction. 807 Apr 80

The effects of angiotensin converting enzyme (ACE) inhibitors on mortality following acute myocardial infarction (MI) has recently been studied in several clinical trials. The rationale for the use of these drugs following an injury to the myocardium is largely based on their ability to attenuate left ventricular volume expansion and modulate neurohormonal activation. Left ventricular dilatation following MI is due to complex structural changes in the infarcted myocardium as well as alterations in the non-infarcted contractile myocardium. The magnitude of this remodelling is associated with adverse prognosis. Neurohormonal systems are activated in the early phase of acute MI. Prolonged neurohormonal activation mainly occurs among patients with marked left ventricular dysfunction. The CONSENSUS II trial examined the effects on mortality of the ACE inhibitor enalapril, when initiated within 24 h from the onset of the infarct and continued for 6 months. There were 6090 patients randomly assigned to placebo (n = 3046) or enalapril (n = 3044). At the end of the trial, 598 patients had died: 286 (9.4%) in the placebo group and 312 (10.2%) in the enalapril group (P = 0.26). These results are in contrast to some other studies in which mortality was reduced by ACE inhibitor therapy post-MI. It is considered likely that the positive effects of ACE inhibitors following MI are confined mainly to patients with marked left ventricular dysfunction and prolonged neurohormonal activation.
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PMID:Left ventricular remodelling, neurohormonal activation and early treatment with enalapril (CONSENSUS II) following myocardial infarction. 807 57

With rapidly progressing therapeutic methods in the cardiovascular medicine, scientific evaluations for newly developed cardiovascular drugs and therapies have become mandatory. We have launched five large scale multicenter cooperative studies, namely, Japan Multicenter Investigation for Cardiovascular Drugs/Therapies, J-MIC (I), (B), (M), (S), and (K). The aims of studies include to investigate: the best therapeutic approach in patients with acute myocardial infarction who underwent thrombolytic therapy with or without any adjunctive treatment (I), the long-term comparative study (3 years) of nifedipine (extended release tablet) with ACE inhibitor in patients with essential hypertension and ischemic heart disease (B), the long-term effect (3 years) of trapidil and/or ethyl icosapentate in patients with ischemic heart disease with or without arteriosclerotic obstructive disease in terms of progression or regression of atherosclerotic changes in coronary as well as peripheral arteries (M), the efficacy and safety of pravastatin to prevent post-PTCA restenosis (S), and regression of atherosclerotic lesion of coronary arteries in patients with familial hypercholesterolemia by LDL apheresis (K).
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PMID:[Large scale multicenter cooperative study for cardiovascular therapy (Japan Multicenter Investigation for Cardiovascular Drugs/Therapies, J-MIC)--results and perspectives]. 807 6

The early administration of nitrates in acute myocardial infarction (AMI) may lower myocardial oxygen demand and increase blood supply to the ischemic myocardium. Actually, nitrates are the drugs most largely used in AMI patients, but no definite proof of their clinical benefits had been reported before GISSI 3 and ISIS 4. Only a meta-analysis of several trials carried out before the thrombolytic era showed that intravenous nitrates and probably oral nitrates can reduce mortality when given early to patients with myocardial infarction. The adjunctive benefit of nitrates in AMI patients receiving the treatments recommended today (thrombolysis, aspirin, beta-blockade) remained undefined. Accordingly, two large controlled randomized studies--GISSI 3 and ISIS 4--were undertaken to verify benefits and risks of nitrate strategy vs ACE-inhibition strategy in AMI. Overall, about 80,000 patients were enrolled. In both studies a small, non significant decrease of mortality was observed in patients allocated to nitrate arms. In GISSI 3, the mortality reduction was greater in patients receiving both nitroglycerin and lisinopril. Either intravenous or by oral or transdermal route nitrates were well tolerated. In conclusion, the systematic administration of nitrates in acute myocardial infarction induces limited benefits in relation to the strategy based on the clinically indicated nitrate administration (applied in 60% of the control patients) but does not bring up risks.
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PMID:[Are nitrates to be recommended in acute myocardial infarct? Towards a conclusive answer]. 808 20

Survival after acute myocardial infarction has been enhanced by treatment with thrombolytic agents, aspirin, and beta-adrenoceptor blockade. However there remains a substantial subgroup of patients who manifest clinical evidence of heart failure despite the first two of these treatments, and for whom beta-adrenoceptor antagonists are relatively or absolutely contraindicated. These patients have a greatly increased risk of fatal and non-fatal ischaemic, arrhythmic, and haemodynamic events. In this selected high-risk subset of patients we investigated the effect of therapy with the angiotensin converting enzyme (ACE) inhibitor rampiril, postulating that it would lengthen survival. 2006 patients who had shown clinical evidence of heart failure at any time after an acute myocardial infarction (AMI) were recruited from 144 centres in 14 countries. Patients were randomly allocated to double-blind treatment with either placebo (992 patients) or ramipril (1014 patients) on day 3 to day 10 after AMI (day 1). Patients with severe heart failure resistant to conventional therapy, in whom the attending physician considered the use of an ACE inhibitor to be mandatory, were excluded. Follow-up was continued for a minimum of 6 months and an average of 15 months. On intention-to-treat analysis mortality from all causes was significantly lower for patients randomised to receive ramipril (170 deaths; 17%) than for those randomised to receive placebo (222 deaths; 23%). The observed risk reduction was 27% (95 % Cl 11% to 40%; p = 0.002). Analysis of prespecified secondary outcomes revealed a risk reduction of 19% for the first validated outcome (i.e., first event in an individual patient)--namely, death, severe/resistent heart failure, myocardial infarction, or stroke (95% Cl 5% to 31%; p = 0.008). Oral administration of rampiril to patients with clinical evidence of either transient or ongoing heart failure, initiated between the second and ninth day after myocardial infarction, resulted in a substantial reduction in premature death from all causes. This benefit was apparent as early as 30 days and was consistent across a range of subgroups.
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PMID:Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. 790 9

The adjunctive use of ACE-inhibitors with thrombolytic therapy early during acute myocardial infarction offers theoretic advantages. In the acute phase, captopril may scavenge free radicals, blunt the catecholamine response, elicit coronary vasodilation and increase prostacyclin and bradykinin levels. In the chronic phase remodelling may be attenuated. At present, a large number of controlled clinical trials mainly focussing on the effects of ACE-inhibition in the chronic phase is under way. Only few studies concentrate on the effect of acute intervention with ACE-inhibitors in ischemia-reperfusion i.e. thrombolysis in myocardial infarction. In the Captopril And Thrombolysis pilot study (CAT pilot-study) 3 mg and 6.25 mg captopril was tolerated well as adjunctive therapy to intravenous streptokinase. Decrease in mean arterial blood pressure (36 +/- 11%) after 6.25 mg was comparable to the control group (30 +/- 7%). Furthermore noradrenaline levels decreased dose dependently to 47 +/- 6 and 38 +/- 7% from baseline respectively. These results prompted a large nationwide acute intervention trial with captopril in 300 patients receiving thrombolytic therapy: the Captopril And Thrombolysis Study (CATS). The primary hypothesis of CATS supposes a very early effect of converting enzyme inhibition on evolving myocardial damage due to ischemia and the consequences of early reperfusion. This will be evaluated by serial echocardiography, Holter monitoring and neurohumoral measurements immediately upon thrombolysis and during the first year after myocardial infarction. Blinded data show a favourable blood pressure response, with systolic hypotension below 100 mm Hg occurring only in 0.2% of patients.
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PMID:Angiotensin-converting enzyme inhibition during thrombolytic therapy in acute myocardial infarction: the Captopril and Thrombolysis Study (CATS). 812 21

Three major trials, in patients with chronic heart failure, have shown that treatment with an ACE inhibitor reduces mortality. However, at the time of writing this review there continue to be strong grounds for uncertainty as to the role of these drugs after acute myocardial infarction in man. This uncertainty is exemplified by the findings of two recently published mortality trials, the CONSENSUS II and the SAVE investigations. Despite virtually identical premises, though widely differing therapeutic approaches, the observations reported in these two papers contrast markedly. In this review we have sought to analyse the possible reasons why the findings of the two trials differ. In our attempt to understand this important issue we have necessarily turned to smaller clinical studies, and also to investigations performed in animals. Furthermore, we review the investigational strategies which have been employed by other, currently unreported, large scale survival studies, as these will certainly hold many of the answers to the questions which the SAVE and CONSENSUS II trials have raised.
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PMID:Inhibition of ACE/kininase-II, acute myocardial infarction, and survival. 814 99


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