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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following the recent demonstration that both cholestyramine and nicotinic acid decrease mortality from coronary heart disease, there is a new enthusiasm for hypolipidaemic therapy. The agents in current use are, however, insufficiently active or are accompanied by unacceptable side effects. An understanding of the mode of action is necessary, both to optimize treatment guidelines (e.g. regarding combination therapy or use in specific subsets of patients) and to develop new agents with preferred actions on rate-limiting steps. A reduction in LDL cholesterol concentration remains the principal desired action, although an elevation in HDL may also be beneficial. The main categories of commercially available agent comprise the anion exchange resins (inhibitors of bile acid absorption); cholesterol absorption inhibitors; fibrates (probably acting by enhancing lipoprotein lipase); and probucol (affecting LDL clearance). The most interesting of the new agents in clinical trials are the beta-hydroxy-beta-methylglutaryl-CoA reductase inhibitors, but other types of agent are at an earlier stage of evaluation, e.g. acyl-CoA: cholesterol acyltransferase inhibitors and peptide cofactors. It is not yet certain whether all the approaches to cholesterol lowering have equal validity, although an effect on biological endpoints is obtained for a variety of agents. Future evaluation will be aided by the implementation of noninvasive methods to quantify atherosclerosis and by the use of simple, 'dry-chemistry', cholesterol assays to screen populations.
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PMID:Mode of action of lipid-lowering drugs. 289 41

The antiatherosclerotic profile of nicotinic acid and of its new water-insoluble derivative was studied in an 8-day experiment in rats. Both drugs lowered plasma triglyceride levels significantly, while other lipoprotein parameters were unaffected. Circulating immune complex levels were decreased with lysosomal membrane permeability by both drugs. Glunicate proved to be a powerful antioxidant with regard to enzymatic lipid peroxidation when studied in the liver microsomal system. The relevance of these findings to the antiatherosclerotic effect of the drugs and the biological significance of antioxidant treatment is discussed. On the basis of these data glunicate seems to be a promising new therapeutic tool against atherosclerosis and merits further study.
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PMID:Hypolipaemic effect and inhibition of lipid peroxidation by glunicate in rats on atherogenic diet. 294 Dec 65

The rationale for drug treatment of patients with hypercholesterolemia is that sustained reductions in the plasma concentrations of atherogenic lipoproteins will retard the development of atherosclerosis. Drug therapy should be initiated only after the exclusion of secondary factors and after an adequate trial of dietary therapy has failed to lower plasma cholesterol to a satisfactory level. The bile-acid sequestrants (cholestyramine and colestipol), nicotinic acid, and lovastatin are the most effective drugs for use in patients with primary hypercholesterolemia; these agents reduce total and LDL cholesterol concentrations by 15-35%. For patients with high concentrations of LDL cholesterol who concurrently have hypertriglyceridemia, nicotinic acid is the drug of choice, and bile-acid sequestrants are contraindicated. Combined therapy with drugs that have different mechanisms of action can be effectively utilized in the treatment of patients with severe hypercholesterolemia; combinations involving lovastatin, nicotinic acid, and bile-acid sequestrants are the most effective.
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PMID:Drug therapy of hypercholesterolemia. 304 95

Nicotinic acid (niacin) is a water-soluble vitamin widely used for the treatment of lipid disorders. In pharmacologic doses (1 g or more/day), alone or in combination with other lipid-lowering drugs, nicotinic acid lowers very low-density (VLDL) and low-density lipoprotein (LDL) levels, while concurrently increasing high-density lipoprotein (HDL) levels. It may reduce long-term mortality in patients with known coronary artery disease and may slow or reverse the progression of atherosclerosis. A major consideration against using nicotinic acid is the occurrence of frequent, bothersome, adverse reactions such as cutaneous flushing, skin rash, and gastric upset. Careful dosing titration may, however, minimize these effects. The beneficial effects, taken together with the low cost of nicotinic acid therapy and the relative freedom from serious side effects, have made nicotinic acid the agent of choice for the treatment of many patients with hyperlipidemia.
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PMID:Nicotinic acid: a review of its clinical use in the treatment of lipid disorders. 267 60

The European Atherosclerosis Society has produced guidelines for the drug treatment of hyperlipidaemia. This, of necessity, is lifelong and therefore should be prescribed only after exclusion of secondary causes for the disorder, after dietary advice has failed to produce desirable plasma lipid levels and after careful consideration of the individual case. A plasma lipid-lowering drug should be efficacious on a long term basis on plasma lipid levels, should fulfil conditions for long term compliance regarding simplicity of administration and lack of subjective side effects, have a documented effect on the clinical endpoint (e.g. myocardial infarction) and be safe on a long term basis. Based on these conditions, plasma lipid-lowering drugs can be classed as first- or second-line treatments. At present, examples of first-line drugs are cholestyramine, nicotinic acid and gemfibrozil, while second-line drugs are lovastatin, simvastatin, probucol and 'third generation' fibrates. With increasing experience with the newer drugs regarding clinical efficacy and long term safety, one hopes that lovastatin, simvastatin and probucol will fulfil all criteria and become first-line drugs. These have advantages over cholestyramine and nicotinic acid in terms of better patient compliance.
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PMID:The future of pharmacological therapy for risk factor reduction. Hyperlipidaemia. 307 15

These studies examine the effects of a hypercholesterolemic diet (with butter and cholesterol added), or a hypertriglyceridemic diet (30% sucrose (w/v) in drinking water), on murine plasma lipids and lipoproteins prepared either by sequential ultracentrifugation or gel exclusion chromatography. The hypercholesterolemic diet increased plasma cholesterol (186%), particularly that associated with very low (VLDL) and low (LDL) density lipoproteins. In addition, the cholesterol/triglyceride ratio in the VLDL fraction rose significantly from 0.10 to 4.0. The hypertriglyceridemic diet raised markedly plasma triglyceride levels (46%) by expanding the circulating VLDL pool (+39%). These dietary modifications were used to provide a model for the examination of 3 classical hypolipidemic drugs (fenofibrate, gemfibrozil and nicotinic acid). In animals receiving the standard diet, fenofibrate, gemfibrozil and nicotinic acid decreased the triglyceride (TG) level (-28%, -31%, and -38%) by lowering VLDL-TG (-37%, -42%, and -49%), fenofibrate and gemfibrozil increased HDL-cholesterol by 18% and 31%, respectively. In animals receiving the hypercholesterolemic diet fenofibrate lowered the total plasma cholesterol level by 40%, at the same time increasing HDL-cholesterol by 23%. In animals fed sucrose, on the other hand, fenofibrate (100 mg/kg per day) and nicotinic acid (900 and 600 mg/kg per day) reduced plasma triglyceride levels (-20%, -40% and -33%), and nicotinic acid (900 mg/kg per day) decreased VLDL-TG by 58%. These results are in good agreement with clinical data from studies in man and suggest that this animal model may provide a useful and rapid screening system for testing new lipid lowering drugs.
Atherosclerosis 1988 Mar
PMID:Effects of fenofibrate, gemfibrozil and nicotinic acid on plasma lipoprotein levels in normal and hyperlipidemic mice. A proposed model for drug screening. 316 79

Carotid bifurcation atherosclerosis was demonstrated in 34 of 108 patients with familial hypercholesterolemia and coronary artery disease by B-scan, continuous-wave Doppler sonography, and intravenous digital subtraction angiography. An intensive combined therapy of diet, colestipol, and nicotinic acid was mounted to control the hypercholesterolemia of these patients. Their serial sonographies and digital subtraction angiography were evaluated independently by technical specialists who served as coinvestigators. The data obtained suggest that extracranial arterial disease can develop concurrently with coronary artery disease in a significant proportion of patients with familial hypercholesterolemia, and amaurosis fugax, transient ischemic attack, cerebral infarction, and myocardial infarction did not recur during 58-72 months of control of familial hypercholesterolemia in this series of patients.
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PMID:Extracranial carotid arterial disease in patients with familial hypercholesterolemia and coronary artery disease treated with colestipol and nicotinic acid. 329 82

Hypercholesterolemia with increased plasma concentrations of low density lipoproteins (LDL) is a major risk factor for the premature development of coronary atherosclerosis in humans and is best exemplified by patients with familial hypercholesterolemia. The recent development of several specific competitive inhibitors of the rate-limiting enzyme in cholesterol biosynthesis (3-hydroxy-3-methylglutaryl-coenzyme A reductase, HMG CoA reductase) has opened up an important new avenue of therapy for patients with hypercholesterolemia who are not responsive to dietary treatment alone. Three drugs, lovastatin (mevinolin), simvastatin (synvinolin) and pravastatin (CS 514), are currently undergoing clinical trials in North America and Europe; the former has recently been approved for general use. Experience with lovastatin and simvastatin in the treatment of patients with primary and secondary causes of hypercholesterolemia is reviewed. The relative potency of simvastatin appears to be greater than that of lovastatin and pravastatin but, with each drug, decreases in the plasma concentrations of LDL cholesterol of 30% to 50% can be achieved. The hypocholesterolemic effects of HMG CoA reductase inhibitors can be potentiated by combination therapy with other approved lipid-lowering medications including the bile acid sequestrants and nicotinic acid. If long-term safety can be satisfactorily established, specific inhibitors of HMG CoA reductase represent a major advance in the therapy of hypercholesterolemia and afford the potential to reduce substantially the high incidence of premature atherosclerosis that occurs in patients with persistent hypercholesterolemia.
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PMID:Hypolipidemic effects of HMG-CoA reductase inhibitors in patients with hypercholesterolemia. 331 47

Recent experimental and epidemiologic evidence has dispelled all doubts about the need to treat patients with hyperlipidemia. Therapy should focus on 3 areas: control of concomitant risk factors for atherosclerosis, reduction of lipid levels through diet and, if response to diet proves inadequate, administration of lipid-lowering agents. There are 4 categories of first-line drugs: resins, fibrates, nicotinic acid and probucol. Probucol has a sustained effect, additive to that of a lipid-lowering diet; it can reduce total serum cholesterol and cause xanthoma regression even in patients with receptor-defective homozygous familial hypercholesterolemia. It is effective when used alone and has an additive effect when combined with resins or nicotinic acid. Compared with many other lipid-lowering medications, it is well tolerated. Although the combination of probucol and clofibrate may cause a significant decrease in high density lipoproteins, there is no evidence that this decrease carries any adverse consequences for the underlying disease process.
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PMID:Medical management of hyperlipidemia and the role of probucol. 346 Mar 20

Drug treatment of patients with hyperlipoproteinaemia is indicated to reduce the risk of atherosclerosis in patients with increased concentrations of atherogenic lipoproteins, and to lower the plasma concentrations of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia who are at risk of abdominal pain and pancreatitis. Such therapy should be initiated only after satisfactory exclusion of secondary causes of hyperlipoproteinaemia, and should be regarded as an adjunct to rather than a substitute for appropriate dietary therapy. Drug therapy should be strongly considered in those patients with concentrations of atherogenic lipoproteins which exceed the 90th to 95th percentile for age. In patients with increased plasma concentrations of low density lipoproteins (LDL), agents which enhance the rate of LDL catabolism (cholestyramine and colestipol) or reduce the rate of LDL synthesis [e.g. nicotinic acid (niacin)] are the 'drugs of choice'. For those patients with concurrent hypertriglyceridaemia, nicotinic acid is the preferred initial drug, and in both patient groups combined drug therapy is often necessary to attain optimal reductions in LDL cholesterol concentrations. Clofibrate remains the 'drug of choice' for the rare patient with type III hyperlipoproteinaemia, whereas the newer agent gemfibrozil should be used in patients with plasma triglyceride concentrations above 1000 mg/dl who are at increased risk of abdominal pain and pancreatitis. Although currently limited to investigational use, mevinolin and related compounds, which are specific inhibitors of the rate-limiting enzyme in cholesterol biosynthesis (HMG Co-A reductase), offer considerable promise in the therapy of patients with primary hypercholesterolaemia due to elevated levels of LDL cholesterol.
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PMID:Lipid-lowering drugs. An overview of indications and optimum therapeutic use. 355 97


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