Management of hypercholesterolemia: approach to diet and drug therapy

Article Abstract:

The gradual accumulation of statistical and biochemical data implicating high serum cholesterol levels in coronary heart disease have, in the past several years, been conclusively confirmed by clinical studies. The National Institutes of Health, the American Heart Association, and the American Medical Association are working to detect and treat adults with elevated levels of low-density lipoprotein (LDL). Dietary intervention is recommended for all adults with low density lipoprotein over 160 milligrams per deciliter (mg/dl), whether or not other risk factors are present. For individuals who already have coronary artery disease, or who have two other risk factors, dietary intervention is recommended for individuals with LDL above 130 mg/dl. Since lipoprotein production is closely linked to caloric intake, a restriction of total calories, best achieved by dietary fat restriction, is recommended. Aerobic exercise should not be overlooked as an important part of a long-term dietary program. If possible, a reduction in saturated fat should be instituted, without necessarily a corresponding increase in unsaturated fat. Although it may be tempting to immediately begin treatment with antihypercholesterolemic drugs, the physician should consider whether the patient has made serious efforts towards changing dietary habits and will be able to make the life-long commitment to drug therapy. The use of drugs is recommended in all individuals with LDL greater than 190 mg/dl. Drugs which sequester bile acids, such as cholestyramine and colestipol, have been thoroughly tested and are widely regarded as safe. Major side effects are largely confined to the gastrointestinal system; the use of a fiber laxative like psyllium may help to relieve constipation. Other drugs include the inhibitors of beta-hydroxy-methylglutaryl coenzyme A reductase. Two such agents, lovastatin and simvastatin, are currently on the market. These drugs are effective and produce few side effects. The acceptance of these drugs by both physicians and patients has been excellent, but any damaging long-term effects are not yet known. Drugs like simvastatin may advantageously be used in combination with bile acid sequestrants for maximal effectiveness in reducing LDL. (Consumer Summary produced by Reliance Medical Information, Inc.)

Colestipol

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Simvastatin: the clinical profile

Article Abstract:

A clinical evaluation of the cholesterol-reducing drug simvastatin involved 1,846 patients with hypercholesterolemia, or high cholesterol levels in the blood. Seventy percent of the participants had the familial or inherited type of hypercholesterolemia. Less than 7 percent experienced any sort of side effect, the most common being headache or constipation. Generally, the side effects were mild enough not to require discontinuation of the drug. Laboratory analysis revealed that some patients experienced an increase in serum levels of the enzyme transaminase. In 0.6 percent of the subjects, this elevation was sufficient to warrant discontinuation. Simvastatin doses of 10 to 40 milligrams per day were effective in reducing serum cholesterol; generally the drug was taken as a single dose in the evening. Evaluation of the drug in patients over 65 years revealed no clinical or laboratory differences from younger patients. The related drug lovastatin has been linked to abnormal muscle changes including pain and weakness, and, in two cases, temporary kidney failure. No such changes have been observed so far in the clinical trials of simvastatin. The beneficial effects and good tolerance of simvastatin should create increasing acceptance of the drug as an effective pharmacologic treatment for hypercholesterolemia. (Consumer Summary produced by Reliance Medical Information, Inc.)

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Efficacy and tolerability of simvastatin (MK-733)

Article Abstract:

To evaluate the effectiveness of simvastatin in reducing serum cholesterol, 43 patients with hereditary hypercholesterolemia were tested in several centers. All subjects were observing a standard lipid-lowering diet and did not receive any drug treatment for six weeks prior to the study. All patients received placebo for two weeks, after which 35 patients were randomly assigned to the simvastatin group and 8 were assigned to a placebo control group. No adverse effects were observed in the simvastatin group, and the patients reported no subjective effects. After 20 weeks, the range of reduction of low-density lipoprotein was from 39 to 71 percent. High-density lipoproteins were elevated by 10 to 14 percent. Different dose ranges were tried; 20 mg per day of simvastatin was more effective than 40 mg per day. A single evening dose seemed to be at least as effective as doses broken up throughout the day. Even in cases of severe hypercholesterolemia, simvastatin can reduce low-density lipoprotein levels to the normal range. (Consumer Summary produced by Reliance Medical Information, Inc.)

Research, Genetic aspects

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