Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

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