Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The current published literature does not indicate whether the long-term effect of anticoagulant or antiplatelet therapy contributes to mortality reduction in patients with LV dysfunction. Evaluating patients for personal risk for emboli or for ischemic coronary artery events may influence the choice of therapies. As more is learned about the mechanisms of drug effects in different populations, physicians may be better able to direct appropriate therapies. Until that time, one must weigh the risks and benefits of each drug alone and in combination. In NYHA class IV patients, the risk for thrombosis owing to spontaneous clotting increases as does the adverse potential of warfarin and the adverse effects of inhibiting prostaglandin mediated vasodilation by aspirin. In NYHA class I and II patients, the quality of life and convenience of multidrug therapy is weighed against the devastating effect of a major stroke. In less symptomatic patients, the long-term risk for acute coronary events may be higher than previously identified. This would suggest that all patients with depressed LV function should be on some type of antiplatelet or anticoagulant therapy. The current WATCH study will provide much needed information about the outcome differences between these agents. Conclusions based on available data include the following: Heart failure is increasing in incidence and prevalence. Atherosclerotic disease is an important causative factor for the development of heart failure or may be a comorbid condition in these patients. There is a measurable rate of stroke in patients with heart failure, although the cause of death in large studies is more often owing to sudden death or progressive heart failure. Sudden death may be from new ischemic events, asystole, or from ventricular tachyarrhythmias. In patients with heart failure, not all strokes are cardioembolic in origin. The benefits and risks of warfarin may be increased as the EF worsens or heart failure functional class declines. The interactions of aspirin and ACE inhibitors have been best evaluated for the hemodynamic effects. There may be additional factors hitherto not studied. The hemodynamic effect of ACE inhibitors may be more important in NYHA classes III and IV than in less symptomatic patients. Warfarin use has clear indications for patients in atrial fibrillation with mechanical prosthetic valves, in hypercoagulable states, and with a previous history of embolization. Aspirin is inexpensive and commonly available, but its use must be evaluated and articulated by the prescribing physician. The current multicenter prospective trials will provide much needed guidance on this subject. The ongoing trials do not have a placebo arm, however, indicating a consensus among clinicians that patients with cardiomyopathy should be on an antiplatelet or anticoagulant drug until further data emerge.
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PMID:To anticoagulate or not to anticoagulate patients with cardiomyopathy. 1171 81

AIM:To assess the effect of ACE inhibitor and Ang II type 1 (AT1) receptor antagonist in preventing hepatic fibrosis caused by CCl(4) administration in rats;to investigate whether or not there are expression of AT 1 receptors on hepatic stellate cells; and to observe the effect of Ang II on proliferation and ECM synthesis of cultured HSCs.METHODS:Studies were conducted in male Sprague-Dawley rats. Except for the hepatofibrotic model group and the control group, in three treated groups, either enalapril (5mg/kg), or losartan (10mg/kg), or enalapril + losartan were given to the fibrotic rats by daily gavage, and saline vehicle was given to model and normal control rats. After 6 weeks, liver fibrosis was assessed directly by hepatic morphometric analysis, which has been considered the gold standard for the quantification of fibrosis. The expressions of AT 1 receptors and (alpha-mooth muscle actin,alpha-SMA) in liver tissue or isolated hepatic stellate cells (HSCs) were detected by immunohistochemical techniques. The effect of Ang II on HSC proliferation was determined by MTT method. Effect of Ang II on collagen synthesis of HSCs was determined by (3)H-proline incorporation.RESULTS:Contrasted to the fibrosis in rats of the model group, groups of rats treated with either enalapril or losartan, or a combination of two drugs showed a limited expansion of the interstitium (4.23 plus minus 3.70 vs 11.22 plus minus 4.79, P<0.05), but no difference was observed among three treated groups (5.38 plus minus3.43, 4.96 plus minus 2.96, 4.23 plus minus 2.70, P>0.05). Expression of AT 1 receptors was found in fibrotic interstitium of fibrotic rats, whereas in normal control rats they were limited to vasculature only to a very slight degree. AT 1 receptors were also expressed on activated HSCs in the culture. At concentrations from 10(-9) to 10(-5)mol/L, Ang II stimulated HSC proliferation in culture in a dose dependent manner. Increasing Ang II concentrations produced corresponding increases in (3)H-proline incorporation. Differences among groups were significant.CONCLUSION:Angiotensin converting enzyme inhibitors and AT 1 blocker may slow the progression of hepatic fibrosis;activated HSCs express AT 1 receptors, and Ang II can stimulate the proliferation and collagen synthesis of HSCs in a dose-dependent manner; and activation of RAS may be related to hepatic fibrogenesis induced by CCl(4).
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PMID:The regulatory role of AT 1 receptor on activated HSCs in hepatic fibrogenesis:effects of RAS inhibitors on hepatic fibrosis induced by CCl(4). 1181 3

Treatment of acute coronary syndrome is under rapid progress. Nevertheless, the early complication rate remains high. Standard antithrombotic treatment is Aspirin 100 mg/d. Patients with elevated risk should be treated with Aspirin and Clopidogrel if primary invasive strategy ist not intended. Independent of the cholesterol level, statins should be given in the early phase of acute coronary syndrome. Dose adaptation is recommended after three months corresponding to the national guidelines. Mainly in diabetes mellitus, additional treatment with an ACE inhibitor lowers the overall cardiovascular risk also in patients without arterial hypertension or congestive heart failure. Six months after the acute event, risk stratification should be adapted.
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PMID:[Secondary prevention after acute coronary syndrome--role of modern drug therapy]. 1188 56

Since coronary artery and cerebrovascular diseases are the most common serious complications of long standing hypertension, there is a great potential for combining treatment with aspirin and angiotensin-converting enzyme inhibitors (ACE-I). However, the data regarding interaction of aspirin and ACE-I in relation to blood pressure control and survival benefits are controversial and inconclusive. We presumed that the appearance of dry cough in some of the patients following initiation of ACE-I treatment could be used as a marker for the presence of their influence, whereas ACE-I cough attenuation after addition of aspirin to treatment could be a sign of aspirin and ACE-I interaction on clinical level. The present study was aimed to use ACE-I induced cough as a clinical marker of ACE-I activity to determine whether dose-dependent aspirin and ACE-I interaction does exist. In a cohort of 750 consecutive ACE-I treated hypertensive and postinfarction outpatients we identified 78 (10.4%) non-smoking ACE-I related coughers. Out of them, 31 (21 men, 10 women; mean age 61 +/- 0.9 years) agreed to take part in the study, which was aimed to compare two regimens of combined ACE-I and aspirin treatment (self-matched control data): intermediate (500 mg daily) vs low-dose aspirin (100 mg daily). On each visit the life quality, cough severity (CS, 0-4) and frequency (CF, 0-10) scores were registered. Low doses of aspirin demonstrated an excellent safety profile and did not influence any life quality score and ACE-I induced cough. In contrast, intermediate doses completely abolished cough in 17 patients and reduced coughing in other 11 patients. Cough severity and cough frequency scores decreased, respectively, from 2.7 +/- 1.1 to 0.7 +/- 1.2 (P < 0.001) and from 7.1 +/- 2.3 to 2.0 +/- 2.2 (P < 0.0001). Overall, the cough frequency score method alone could identify a clear modification of cough in 26 (84%) patients, and cough severity score method alone in 24 (77%). Using the combined frequency/severity score method a modification of cough could be identified in 28 (90%) of the patients receiving intermediate dose of aspirin. Aspirin did not influence heart rate and blood pressure control either in hypertensives or in postinfarction patients. We conclude that using ACE-I induced cough as a clinical marker of ACE-I activity demonstrates that an interaction between ACE-I and aspirin at 500 mg/day does exist. We did not find any evidence supporting the presence of a clinically significant interaction between ACE-I and aspirin at 100 mg/day. Thus, combined treatment by low dose aspirin and ACE-I seems to be both safe and useful.
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PMID:Clinical evidence of dose-dependent interaction between aspirin and angiotensin-converting enzyme inhibitors. 1203 91

Essential hypertension is one of the most important risk factors for cardiovascular diseases. Its pathophysiological mechanism is unknown. Recent data suggests that deformability and aggregation of red blood cells may play an important role in the regulation of blood rheology in hypertension. Simultaneously there are reports suggesting that antihypertensive effects of angiotensin converting enzyme inhibitors (ACEI) could be counteracted by high doses of aspirin. We postulate that these effects could be related to the changes in blood rheology. Accordingly we designed a study to evaluate the effect of low or high dose of aspirin on deformability and aggregability of red blood cells from patients with essential hypertension. Deformability and aggregability of red blood cells were measured by laser diffractometer (Rheodyn SSD, Myrenne GmbH) and computerized automatic aggregometer (MA1 Myrenne GmbH, Germany), respectively. The effects of aspirin on deformability and aggregation of red blood cells were studied ex vivo in whole blood from three groups of patients with essential hypertension (group I: 10 patients receiving placebo, group II: 23 patients receiving 75 mg/day p.o. aspirin for 3 days, and group III: 23 patients receiving 300 mg/day p.o. aspirin for 3 days). Subjects in all groups received the same combination of antihypertensive agents consisting of: one of ACEI (enalapril or perindopril), one of beta-antagonists (metoprolol or bisoprolol), and diuretic agent (indapamid). In patients receiving high dose of aspirin (300 mg/day) we observed that erythrocyte aggregability was 25% higher than in the placebo group (MEA = 25.8 +/- 6 SD, vs MEA = 20.6 +/- 3 SD, p < 0.05). Aspirin had no effects on deformability of erythrocytes or on arterial blood pressure. High doses of aspirin or possibly also other nonsteroidal anti-inflammatory drugs (NSAID) in patients receiving antihypertensive therapy can directly affect rheological properties of the blood due to the activation of red blood cell aggregation. Increased aggregation of red blood cells during antihypertensive therapy may be an important indicator of the worsening of organ perfusion.
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PMID:[The effect of aspirin on rheological properties of erythrocytes in essential hypertension]. 1215 52

Heart failure (HF) is a disease which is prevalent in the elderly. Concomitant rheumatological diseases are also prevalent in this population which require treatment with NSAIDs. Aspirin is also routinely used for the primary and secondary prevention of coronary artery disease (CAD) which is a common cause of HF. ACE inhibitors are the cornerstone of drug therapy in managing patients with HF. Elderly patients with HF are frequently encountered with multiple drug therapy, such as nonsteroidal antiinflammatory drugs (NSAIDs) including aspirin and ACE inhibitors. In recent years there has been a concern of negative interaction between these two common drug therapies in patients with HF which may subsequently attenuate the beneficial effects of ACE inhibitors. Whereas some studies have shown that the coadministration of NSAIDs including aspirin with ACE inhibitors might diminish the degree of improvement in cardiovascular hemodynamics and adversely affect renal functions, other studies have failed to substantiate this. Furthermore, although potential opposing effects of NSAIDs and ACE inhibitors on prostaglandin synthesis has been cited as the mechanism responsible for the negative interactions, more work is needed in this area to better define the precise reasons responsible for it. However, based on the available data thus far, it is prudent to be aware of such negative interaction and especially in case of aspirin to avoid it by using relatively lower dosage. (c)1999 by CHF, Inc.
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PMID:Pharmacotherapy in congestive heart failure: Do NSAIDs attenuate the therapeutic effect of ACE inhibitors in heart failure patients? 1218 5

Stroke is a major cause of morbidity and mortality. Full assessment of stroke or transient ischaemic attack (TIA) patients is required to identify all risk factors and apply appropriate secondary preventative strategies. Antiplatelet therapies are effective in the secondary prevention of ischaemic stroke and can be justified despite adverse effects such as gastrointestinal haemorrhage. Aspirin (acetylsalicylic acid), aspirin plus dipyridamole, ticlopidine and clopidogrel are all of value but their adverse effect profiles vary significantly. Combinations of antiplatelet agents may offer additional benefit but not all combinations have been studied in stroke patients. Anticoagulation with agents such as warfarin is effective with coexisting atrial fibrillation and other conditions predisposing to cardioembolic stroke. Antihypertensive agents have been extensively studied in the primary prevention of stroke; however, relatively few trials of antihypertensive agents in the secondary prevention of stroke are available. The incidence of adverse effects of antihypertensive agents is relatively low and the benefit-risk profile would tend to favour their use in the secondary prevention of stroke. Recent studies of ACE inhibitors have identified an important role for these agents in the secondary prevention of stroke even in those who are normotensive and in those who have had a haemorrhagic stroke. The incidence of serious adverse effects with ACE inhibitors appears relatively low. Lipid-lowering agents may have a role to play in certain groups of patients with stroke. The incidence of adverse effects is relatively low with HMG-CoA reductase inhibitors. Cigarette smoking is an important risk factor for stroke and evidence is available that smoking cessation does reduce the individual's risk of stroke. Pharmacological agents are available to help smoking cessation. In patients with diabetes mellitus, intensive regimens with insulin and oral hypoglycaemic agents have so far not definitively been shown to reduce the incidence of macrovascular complications such as stroke. Tight glycaemic control has been shown to improve microvascular complications such as retinopathy, nephropathy and neuropathy and hence this is reason enough to advocate the use of these agents. Future developments in the treatment of diabetes may help. Secondary prevention of stroke has improved greatly over the past decade and hopefully will continue to improve. The use of pharmacological agents available currently and in the future will be clarified and refined as further clinical trials report.
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PMID:A benefit-risk assessment of agents used in the secondary prevention of stroke. 1238 Dec 15

Cardiovascular disease is the leading cause of death in Europe. Acute myocardial infarction (AMI) is among the most common of its manifestations. Women and older patients are under-represented in most trials of treatment for AMI, as are those with significant co-morbidities. These patients also have a worse long term outcome after AMI. We sought to evaluate the management of AMI in a small non-academic general hospital. A review was performed of cases of AMI during 2000. Ninety-two cases were analysed, 69% were male. The mean age was 70 years. In-hospital mortality was 12%; 30-day mortality was 14%. There was no gender or age difference in mortality. Of thirty eligible patients, twenty-eight were thrombolysed (93%). Aspirin (81%) and beta-blocker (41%) prescription on discharge were below published European and American rates. Females were significantly less likely to receive aspirin or beta-blockers on discharge. Those aged 70 years or more were less likely to receive beta-blockers, statins or ACE inhibitors on discharge. Those with co-morbidities were less likely to receive beta-blockers or statins on discharge. This study highlights the difficulty in realising evidence based guidelines optimal management of AMI in clinical practice. While the outcome with regard to mortality is similar to national figures, there is a need to enhance care, with particular emphasis on secondary pharmacological measures prescribed on discharge.
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PMID:The management of acute myocardial infarction--practical problems in implementing the evidence. 1246 97

Treatment of acute coronary insufficiency in diabetics--recent myocardial infarction (MI--unstable angina--uses the same modalities as in the absence of diabetes. Thrombolytics improve the prognosis of MI, although the hospital mortality remains about two fold in the presence of diabetes. Primary angioplasty has an identical success rate, but restenoses are significantly more frequent in diabetics. Systematic use of stents allows a reduction of the restenosis rate to the level observed in the absence of diabetes. In unstable angina, low molecular weight heparins have an efficacy and a safety identical to those observed in non-diabetic patients. There is therefore no limitation to their use. Diabetics present permanent activation of blood platelets which promotes their adhesion and aggregation. Aspirin must therefore be systematically prescribed to diabetic patients, except in the presence of a contraindication, especially gastrointestinal, in which case, ticlopidine can be used. Platelet glycoprotein IIB-IIIA receptor inhibitors have the same indications and provide the same results as in the absence of diabetes. Contrary to a widely held belief, beta-blockers, especially cardioselective, can be widely used in diabetics. The same applies to angiotensin converting enzyme inhibitors. Finally, during the acute phase of coronary insufficiency, continuous insulin infusion via a pump ensures better control of diabetes and also decreases the mortality of MI. Permanent collaboration between cardiologists and diabetologists is therefore essential to increase the efficacy of treatment and to improve the prognosis of acute coronary insufficiency in diabetic patients.
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PMID:[Treatment of coronary insufficiency in diabetics: Part 2: acute coronary insufficiency]. 1255 36

In Colombian populations older than 15 years, 12.6% suffer from hypertensive disease. Pharmacological therapies for hypertension and associated diseases were compared for 11,947 adult hypertensive patients of both sexes. All had been in treatment for more than 3 months (November/01-January/02), and were distributed among six Colombian cities. The data were retrieved from medication consumption registers that were maintained by the institutions that distribute medications to patients selected for the study. The average age of patients was 55.8 +/- 13.8, and 67.7% were women. Men were older (p < 0.05) and consumed other drugs more than women (67.7% vs. 62.4%, p < 0.05); 53.2% of patients received only one drug and 46.8% received between 2 to 5 drugs for hypertension disease. Medications most commonly prescribed were hydrchlorothiazide (31.8%), captopril (27.9%), verapamil (27.6%), enalapril (25%), metoprolol (15.1%) and propranolol (14.9%). The most common combinations were hydrochlorothiazide + ACE inhibitors (n = 2,001), hydrochlorothiazide + calcium channel antagonists (n = 1,367), verapamil + ACE inhibitors (n = 1,153) and hydrochlorothiazide + beta blocker (n = 1,021). Other prescribed medications included ASA as antiplatelet (38.2% of patients), nonsteroidal anti-inflammatory drugs (NSAID, 16.2%), lipid-lowering drugs (11.8%), hypoglycemic agents (10.9%) and antiulcerous drugs (9.6%). Some agents are probably underemployed (ACE inhibitors, ASA) and others overused (antiulcerous). Potentially dangerous pharmacological interactions were discovered in 410 cases (3.43%). Significant differences occurred in physicians' formulations among the six cities, but rational prescription patterns prevailed. Newly designed educational strategies are recommended to prevent administration of potential harmful combinations. Further exploration of clinical results in these formulations is indicated.
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PMID:[Patterns of antihypertensive agents use in 11,947 Colombian patients]. 1259 45


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