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)

Following establishment of its efficacy in hypertension and congestive heart failure, the ACE inhibitor lisinopril has now been shown to reduce mortality and cardiovascular morbidity in patients with myocardial infarction when administered as early treatment. The ability of lisinopril to attenuate the detrimental effects of left ventricular remodelling is a key mechanism; however, additional cardioprotective and vasculoprotective actions are postulated to play a role in mediating the early benefit. The GISSI-3 trial in > 19 000 patients has demonstrated that, when given orally within 24 hours of symptom onset and continued for 6 weeks, lisinopril (with or without nitrates) produces measurable survival benefits within 1 to 2 days of starting treatment. Compared with no lisinopril treatment, reductions of 11% in risk of mortality and 7.7% in a combined end-point (death plus severe left ventricular dysfunction) were evident at 6 weeks. Advantages were apparent in all types of patients. Thus, those at high risk-women, the elderly, patients with diabetes mellitus and those with anterior infarct and/or Killip class > 1 -also benefited. These gains in combined end-point events persisted in the longer term, despite treatment withdrawal after 6 weeks in most patients. At 6 months, the incidence rate for the combined end-point remained lower than with control (a 6.2% reduction). The GISSI-3 results concur with those from recent large investigations (ISIS-4, CCS-1, SMILE) of other ACE inhibitors as early management in myocardial infarction. However, the results of the CONSENSUS II trial (using intravenous enalaprilat then oral enalapril) were unfavourable in some patients. These findings, together with the development of persistent hypotension and, to a lesser extent, renal dysfunction among patients in the GISSI-3 trial, have prompted considerable debate over optimum treatment strategies. Present opinion generally holds that therapy with lisinopril or other ACE inhibitors shown to be beneficial may be started within 24 hours in haemodynamically stable patients with no other contraindications; current labelling in the US and other countries reflects this position. There is virtually unanimous agreement that such therapy is indicated in high-risk patients, particularly those with left ventricular dysfunction. The choice of ACE inhibitor appears less important than the decision to treat; it seems likely that these benefits are a class effect. Lisinopril has a tolerability profile resembling that of other ACE inhibitors, can be given once daily and may be less costly than other members of its class. However, present cost analyses are flawed and this latter points remains to be proven in formal cost-effectiveness analyses. In conclusion, early treatment with lisinopril (within 24 hours of symptom onset) for 6 weeks improves survival and reduces cardiovascular morbidity in patients with myocardial infarction, and confers ongoing benefit after drug withdrawal. While patients with symptoms of left ventricular dysfunction are prime candidates for treatment, all those who are haemodynamically stable with no other contraindications are also eligible to receive therapy. Lisinopril and other ACE inhibitors shown to be beneficial should therefore be considered an integral part of the early management of myocardial infarction in suitable patients.
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PMID:Lisinopril. A review of its pharmacology and clinical efficacy in the early management of acute myocardial infarction. 889 68

In symptomatic endstage coronary artery disease after full medical therapy (antianginal drugs, betablockers and ACE-inhibitors) further therapeutical options both for the interventional cardiologist with little hope for improvement by PTCA, stent, rotablation and atherectomy and for the cardiac surgeon with bypass surgery and endarterectomy are not available by definition due to the diffuse arteriosclerotic vessel morphology. In those patients one can therefore consider transmyocardial laser therapy (TMR) as the ultimate treatment option. It then is primarily a palliative measure to reduce the patient's symptoms. Improving perfusion and prognosis remains the most important goals, however. TMR can be utilized as the only revascularizing treatment measure or in combination with CABG or PTCA. According to data from international registries, few controlled and several non controlled studies and our own registry in Marburg with now 101 patients improvement of angina and/or dyspnoea can be expected in more than 60% of patients with end stage coronary artery disease (CAD). The patient cohort comprises symptomatic individuals after CABG or multiple PTCAs or with diffuse CAD in diabetes mellitus or with most severe hypercholesterinemia. We consider these above mentioned criteria as the only validated criteria to enter patients with endstage CAD in our controlled study. Hypothetical options for treatment by TMR such as vasculopathies after heart transplantation, cardiomyopathies under the notion of a possible but not proven microangiopathy are not accepted in our institution at present. Before TMR all patients are assessed for their angina class according to the Canadian Cardiac Society (CCS I-IV)) and their exercise capacity according to the New York Heart Association classification (NYHA I-IV) and reassessed regularly after 3, 6 and 12 months. Thallium/Te MIBI scans at rest- and whenever possible at exercise as well as stress echocardiography are carried in the patients to assess symptomatic improvement, alterations in myocardial perfusion and functional efficacy by TMR. By intermediate analysis the 101 patients of our registry more than 60% of the patients had improved their angina class by at least one classe, some patients have improved perfusion as assessed by scintigraphy, which makes at present a trend but not yet a significant difference, whereas central hemodynamics and ejection fraction remained virtually unchanged in most patients reassessed after TMR. In our analysis mortality of the 101 TMR patients was assessed and plotted on Kaplan Meier survival curves. Mortality at 6 months was 11%. When compared to a historical group of patients with identical CCS and comparable NYHA classes, who were worked up in the manner of a case control study, the TMR mortality was marginally but not yet significantly lower than one would expect from these control patients with terminal CAD treated purely by medication: Their 6 months mortality was 14%. Remarkably but not unexpectedly patients with comparable CCS classes, who could still be treated by PTCA and/or CABG had a significantly lower 6 months mortality than TMR patients or patients on antianginal drugs only. The pathophysiological mechanisms for the symptomatic improvement by laser therapy are not yet fully understood. The 1 mm transmyocardial channels created by the CO2 laser have been postulated to permit perfusion from the ventricular cavity and to seek connection to capillaries and vessels present in the malperfused myocardium thus improving the perfusion by newly created connections and sinusoids from the ventricular cavity. Although there is clear evidence for the presence of open channels acutely and within a few days after TMR therapy little evidence in man is as yet available on the question whether the channels remain open in the long run and, if so, whether they can actually improve perfusion to a substantial degree...
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PMID:[Indications for transmyocardial laser therapy]. 906 76

Recent trials have shown that ACE-inhibitors are safe and can reduce mortality and the occurrence of severe left-ventricular dysfunction (LVD) (when started within the first day after acute myocardial infarction (MI) and continued for 4 to 6 weeks thereafter). GISSI-3, ISIS-4 and CCS-1 studies show that more than half of the lives are saved by ACE-inhibitor treatment within the first week of therapy. Although the benefit from ACE-inhibitor is larger in patients presenting with congestive heart failure (Killip class >1), the number of lives saved in patients at low risk, who represent the majority of the population, is relevant. This supports the approach of treating all hemodynamically stable MI patients. Treatment could be stopped after about 1 month in patients without evidences of LVD while those with LVD should be continued on ACE-inhibitors for a long period of time.
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PMID:Very early administration of ACE-inhibitors in acute myocardial infarction. 970 29

Eight randomised clinical trials of angiotensin converting enzyme (ACE) inhibitors versus placebo in myocardial infarction have been published in three years, including over 100,000 patients. High risk myocardial infarction carries a poor prognosis with a 25% death rate at 42 months in SAVE, 23% at 15 months in AIRE and 42% at 37 months in TRACE. This form of myocardial infarction benefits the most from treatment with ACE inhibitors: the relative reductions in risk for the previously mentioned trials were 19%, 27% and 22% respectively, and the absolute reductions in risk of death were 4% at 42 months, 6% at 15 months and 8% at 37 months, respectively. Studies including all forms of myocardial infarction involve populations at lower risk. The effects of ACE inhibitors on mortality are then less obvious: from 7.7% to 7.2% at 5 weeks in ISIS-4, from 7.1% to 6.3% at 6 weeks in GISSI-3, from 9.6% to 9.0% at 4 weeks in CCS-1, corresponding to relative reductions in the risk of death of 7%, 12% and 3% respectively and absolute reductions of the risk of death of 0.5% at 5 weeks, 0.8% at 6 weeks and 0.6% at 4 weeks, respectively. Who should be treated? All patients for 4 to 6 weeks or only high risk patients. When should treatment be started? Some investigators institute treatment from the first day but others think it prudent to wait until the second day. For how long? Four to 6 weeks would be sufficient to counteract ventricular remodelling while the benefits are sustained in the long term. But treatment should be continued long term in high risk patients. Which molecule, which dose and how many times, should it be taken per day? The logical answer is molecules with proven efficacy at the dose given in the clinical trials respecting the number of times indicated per day.
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PMID:[Treatment with angiotension converting enzyme inhibitors]. 974 77

This study aimed at analysing an effect of the coronary risk factors and pharmacotherapy on the long-term outcome in women following the coronary artery by-pass. In 1004-1997, 253 female patients, aged between 33 and 82 years (mean [+/- SD] 57.0 +/- 8 years) were treated surgically. The follow-up period lasted for 7 to 60 months (mean 32.0 +/- 14 months). Ten patients (3.9%) died. Answers to the questionnaire and personal interviews assessed physical fitness based on CCS classification, pharmacotherapy, and presence of risk factors. According to CCS scale, significant improvement has been seen in 195 (82.6%; p < .0001) patients. Health state did not change in 34 (14.4%) patients, and deteriorated in 7 (3.0%). Analysisn coronary risk factors, hypertension proved prevailing (60.3%), followed by diabetes mellitus (25.5%) and obesity (22.9%). Eleven percent of patients returned to cigarettes smoking after surgery. Postoperatively, 74.1% of patients received nitrates as a constant, medication, 58.2%--beta-blockers, 53.4%--ACE inhibitors, and 19.8% of patients received calcium antagonists. Lipid abnormalities have been treated in 49.1% of patients whereas antiplatelet therapy has been carried out in 74.1%. Only 9.9% of patients received hormones. The lower CCS class before surgery, the more significant improvement after it. As pharmacotherapy was used according to the European guidelines, an improvement in the long-term outcome required some modifications in patients' life style.
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PMID:[An influence of cardiovascular risk factors and pharmacotherapy on the long-term results in women undergoing coronary artery bypass]. 1080 40

Angiotensin II (AT II) is a final product of the renin-anglotensin-aldosterone system (RAS) and presents one of the most influential factors in the pathogenesis of atherosclerosis, acute coronary syndrome, myocardial dysfunction and heart failure. ACE-inhibitors (ACEI), beside beta adrenergic blockers, are a cornerstone of the current chronic heart failure (CHF) treatment. Evidence based medicine has not yet proved any significant beneficial effects of ACEI in patients with unstable angina pectoris (UAP), although according to the SoLVD study testing the possible effects of ACEI in patients with significant left ventricular dysfunction and/or CHF, there was a significant hospitalization rate reduction as well as less transformation of UAP to myocardial infarction in patients treated with ACEI. In the GISSI 3, ISIS 4 and CCS studies, ACEI was given within the first 24 hours and continued for 4-6 weeks. According to pooled results, ACE inhibitor could save 11/1000 patients with ST-elevation myocardial infarction (STEMI) and only 1/1000 patients with non ST-elevation myocardial infarction (NSTEMI). In the SAVE, AIRE and TRACE studies, ACEI was started later, i.e. 3-16 days after acute myocardial infarction and continued for several years. ACEI therapy resulted in a significantly lower mortality during the first year, and an even 20% relative reduction in the total mortality during the 4-year follow up. The effects of ACEI were even more prominent in more severe myocardial dysfunction, as it was well known that they could slow or stop unfavorable myocardial remodeling. Conclusively, ACEI should be given as early as possible to all patients with acute myocardial infarction, if no contraindications. The HOPE study showed efficacy of ACEI in the primary prevention of ischemic heart disease in high risk individuals, and the EUROPA study showed a favorable effect of ACEI in the secondary prevention of ischemic heart disease in low risk patients. According to these findings, ACEI should be given permenantly following myocardial infarction. These findings suggest the need of a permanent treatment with ACEI in patients having sustaned myocardial infarction. Angiotensin-1 receptor antagonists (AT-1 antagonists) are a newer generation of neurohormonal antagonists, which block the effects of AT II produced not only through a classic, ACE-dependent pathway but also via alternative pathways (non ACE-dependent) and selectively bind to AT-1 receptors for AT II. Therefore, they have some theoretical advances in comparison with ACEI. There are 2 relevant studies elucidating their possible role in treating patients with or post-myocardial infarction. The OPTIMAAL study did not prove losartan to be better than an ACEI (captopril), while the VALIANT study showed that the effects of valsartan vs. captopril were statistically nonsignificantly different. Furthermore, there is no sense to combine AT-1 antagonist and ACEI, while a combination of AT-1 antagonist and a beta blocker is justified. In other words, AT-1 antagonist (the class effect is disputable) should be given to patients with acute myocardial infarction or to post-myocardial infarction patients who cannot take ACEI.
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PMID:[ACE inhibitors and angiotensin II receptor antagonists in acute coronary syndrome]. 1520 98

Ventricular remodeling can play a detrimental role in the progression of cardiovascular diseases, leading to heart failure. The current study was designed to investigate the effects of 17beta-estradiol (E2) on cardiac remodeling. Cardiac fibrosis and hypertrophy were examined in deoxycorticosterone acetate (DOCA)-salt treated rats with chronic, six-week administration of two different doses of E2. Bilaterally ovariectomized (Ovex) female Sprague-Dawley rats were randomly assigned to one of the following groups: Ovex-control; Ovex-DOCA; Ovex-DOCA+low-dose E2 (1.66 microg/day); or Ovex-DOCA+high-dose E2 (2.38 microg/day). All DOCA-treated rats were uninephrectomized and drinking water was replaced by 0.15M NaCl solution for the remainder of the study period. DOCA-salt treatment resulted in a significant increase in blood pressure, which was not altered by estrogen replacement. Histological examinations revealed marked cardiac remodeling (both ventricular hypertrophy and interstitial fibrosis) with DOCA treatment, which was attenuated in animals receiving estrogen therapy. Western blot analysis demonstrated increased cardiac levels of angiotensin converting enzyme (ACE) with DOCA treatment, which was attenuated by E2 replacement. Furthermore, increased levels of cardiac angiotensin converting enzyme 2 (ACE2) protein were observed in animals receiving high-dose E2 replacement. These findings suggest that physiologically relevant estrogen replacement therapy has blood pressure-independent cardioprotective effects, which are possibly mediated through modulation of the cardiac renin-angiotensin system.
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PMID:17beta-Estradiol modulates local cardiac renin-angiotensin system to prevent cardiac remodeling in the DOCA-salt model of hypertension in rats. 1974 16