Influence of pravastatin, a specific inhibitor of HMG-CoA reductase, on hepatic metabolism of cholesterol

Article Abstract:

Elevated levels of serum cholesterol are a primary risk factor for the development of atherosclerosis and coronary heart disease. More specifically, the risk is associated with elevated levels of low-density lipoprotein (LDL) cholesterol. For this reason, there has been extensive research on the metabolism of LDL cholesterol. Anticholesterol drugs generally work by inhibiting an enzyme involved in cholesterol synthesis. The enzyme, 3-hydroxymethyl-3-methylglutaryl coenzyme A reductase, mercifully abbreviated HMG-CoA reductase, is the rate limiting step in the manufacture of cholesterol; any inhibition of this enzyme should result in decreased cholesterol output. To further elucidate the details of cholesterol metabolism, the effects of pravastatin, an HMG-CoA reductase inhibitor, were observed in patients awaiting surgery for gallstones. The study directly demonstrated the inhibition of the enzyme. Furthermore, the results confirmed that the observed decrease in cholesterol was due to decreased synthesis, and not some other cause. This was possible by measuring the amount of lathosterol, which is an intermediate compound partly down the assembly line of cholesterol production. Since lathosterol was also reduced in the treated patients, it seemed clear that the cholesterol-synthesizing machinery was working at reduced capacity. An important observation of this study was that the binding activity of LDL receptors on the liver was almost doubled. This would increase the rate at which LDL cholesterol is removed from the circulation and broken down, and in no doubt is a significant aspect of the mechanism by which anticholesterol drugs exert their beneficial effects. (Consumer Summary produced by Reliance Medical Information, Inc.)

Physiological aspects, Cholesterol, Anticholesteremic agents

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Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia

Article Abstract:

Pravastatin may reduce the risk of heart attack and death from cardiovascular causes in men with high levels of cholesterol in their blood. In a group of men with an average cholesterol level of 272 milligrams per deciliter of plasma, 3,302 received 40 milligrams of pravastatin and 3,293 received a placebo. During an average follow-up of 4.9 years, researchers reviewed medical records, and conducted physical exams and blood tests. Cholesterol levels decreased by 20% in the pravastatin group, but did not change in the placebo group. The risk of having a nonfatal heart attack or dying of coronary heart disease decreased by 31% in the pravastatin group. The risk of death from noncardiovascular causes was equal in the pravastatin and placebo groups. The risk of dying from any cause was reduced by 22% in the pravastatin group. Side effects in both groups included muscle pain, and elevated levels of liver enzymes and the waste product creatinine kinase.

Prevention

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Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels

Article Abstract:

The cholesterol-lowering drug pravastatin can reduce mortality rates as well as the rate of heart attack and stroke in patients with coronary heart disease. Researchers randomly assigned 9,014 patients to take pravastatin or a placebo every day for an average of six years. All patients were advised to follow a low-fat diet. Overall mortality was reduced 22% in those taking pravastatin and mortality from coronary heart disease was 24% lower in this group. The rate of heart attacks and strokes was also lower in the patients taking pravastatin.

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