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Statins

A class of cholesterol-lowering drugs, also known as HMG-CoA reductase inhibitors. Statins work by blocking the action of an enzyme that controls the production of cholesterol. By slowing down cholesterol production, they improve the liver’s ability to clear cholesterol from the blood. Statins are the first-choice drug for treating elevated low-density lipoprotein (LDL, or “bad”) cholesterol levels, and they have relatively few immediate, short-term side effects. There are currently six statin drugs available in the United States: lovastatin (brand name Mevacor), pravastatin (Pravachol), simvastatin (Zocor), atorvastatin (Lipitor), fluvastatin (Lescol), and rosuvastatin (Crestor). A seventh statin, cerivastatin (Baycol), was removed from the market in 2001 because of its link to 31 deaths from rhabdomyolysis, a condition of severe muscle deterioration.

People with Type 2 diabetes are prone to dyslipidemia, or abnormal blood lipid levels, characterized by smaller, denser particles of LDL cholesterol, relatively low levels of high-density lipoprotein (HDL, or “good”) cholesterol, and high levels of fatty substances called triglycerides. Having dyslipidemia raises a person’s risk of atherosclerosis, heart disease, and stroke. Diabetes itself is also an independent risk factor for heart disease.

The American Diabetes Association recommends that adults with diabetes have their LDL, HDL, total cholesterol, and triglyceride levels checked every year. Treating LDL cholesterol is the first priority in lipid management. If a person’s LDL level is greater than or equal to 100 mg/dl, the first treatment recommended is dietary modifications, along with increased physical activity and improved blood glucose control. However, if the LDL level is 100 mg/dl or higher and the person has existing heart disease, peripheral vascular disease, or cerebrovascular disease, drug therapy should be started in addition to lifestyle changes. Drug therapy should also be started immediately in anyone whose LDL is 130 mg/dl or higher, whether or not the person has existing cardiovascular disease.

Statins are considered the first-choice drug for lowering LDL cholesterol levels, but other types of drugs may be added to achieve secondary goals, such as raising HDL cholesterol levels or lowering triglyceride levels. Other classes of cholesterol-fighting drugs include resins, such as cholestyramine (Questran) and colestipol (Colestid), which lower LDL cholesterol; fibrates, such as gemfibrozil (Lopid), fenofibrate (Tricor), and clofibrate (Abitrate, Atromid-S), which lower triglycerides and to some degree raise HDL cholesterol; and high doses of the B vitamin nicotinic acid, or niacin, which can improve all lipid levels.

In November 2001, at the annual meeting of the American Heart Association, researchers announced the results of the Heart Protection Study, the largest study yet on cholesterol-lowering therapy. The 5 1/2-year study, which followed more than 20,000 people with risk factors for heart disease (such as diabetes, hypertension, a history of heart attack, stroke, or blocked arteries elsewhere in the body) showed that participants who were given simvastatin reduced their risk of heart attack or stroke by one-third. One interesting finding of the study was that simvastatin substantially reduced these risks even in people who had relatively normal cholesterol levels to begin with, which suggests that the drug may benefit an even wider range of people than had previously been thought. Blood tests showed that simvastatin was safe and did not increase the risk of liver or muscle damage or cancer.

In other large trials, similarly positive results have been shown for other statins, particularly lovastatin and pravastatin; these three are the most commonly used statins.

While the various statins are prescribed more or less interchangeably, some differences among them have been noted. One recent trial found that atorvastatin did a better job of improving a person’s overall lipid profile than simvastatin. Simvastatin appears to be the most effective of the statins at raising HDL cholesterol; pravastatin is least likely to interact with other drugs; and lovastatin is the first to have been approved for a generic version, making it the most accessible.

Statins may provide heart protection beyond lowering cholesterol: They appear to reduce inflammation and clot formation in the arteries and to stimulate the release of protective nitric oxide within the blood vessels. In one recent study, people who discontinued statins were three times more likely to have a heart attack than those who continued to take their medicine, a finding that seems to confirm that the drugs provide profound protection against cardiovascular disease.

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