Cholesterol-lowering drugs have variety of potential uses

December 25, 2005|By RONALD KOTULAK

CHICAGO -- Not since aspirin has a class of drugs come along that does so much more than originally intended that it could end up being used as a preventive against many major diseases.

Statins, which lower cholesterol, have been proved in clinical trials to reduce heart attacks and strokes by 30 percent to 50 percent. They are the most widely prescribed drugs in the United States; one in 10 adults takes them.

But their full value in improving the nation's health rests with research attempting to establish the ability of statins to prevent cancer, Alzheimer's disease, diabetes, osteoporosis, high blood pressure, multiple sclerosis and macular degeneration.

Observational studies suggest that people who take statins are at lower risk of developing those illnesses. Researchers are exploring why the drugs might have such a broad protective effect and are finding that the drugs may affect critical systems of the body in ways that head off disease.

"Statins are one of the real miracle drugs from the last generation of research," said Dr. Thomas H. Lee, a cardiologist at Harvard Medical School and Brigham and Women's Hospital. "No one realized when they came out just how broad their impact would be. There are reasonable people who believe that if statins were completely free, everyone should take them."

Lee and others caution, however, that the drugs still must undergo rigorous clinical trials to prove that they can safely do all the things they have been billed to do.

"If we determine down the road that statins help reduce things like Alzheimer's disease, osteoporosis and cancer, they still should be given to people who are at higher risk of developing those things, [rather] than just to everybody across the board," said Dr. Matthew Sorrentino, director of preventive cardiology at the University of Chicago.

Statins are taken to lower levels of cholesterol, especially low-density lipoprotein or LDL, the "bad cholesterol" linked to heart disease. They do that work very well.

Cholesterol, which is made naturally in the liver, is a vital component used to build all cells in the body and to maintain their function. It becomes dangerous when blood levels are too high - usually because of diet - and excess cholesterol builds up in artery walls, causing heart disease.

Statins work against cholesterol in two ways: They reduce the liver's ability to manufacture it, and they speed the elimination of LDL from the body.

But researchers are discovering that statins have other surprising effects. In reducing cholesterol, the drugs set in motion a chain of events that appears to improve many functions in the body, including blood pressure and inflammation.

A long series of chemical steps leads up to the manufacture of cholesterol, and each of those steps plays a role in cellular function. Trouble appears to occur when cholesterol levels get too high and the chemical steps behave abnormally, helping to set the stage, scientists believe, for such disorders as cancer, heart disease and Alzheimer's.

By slowing the first step of the chemical pathway to cholesterol production, statins help prevent that from happening.

Evidence suggests that statins thereby help the body in many ways, such as getting rid of cancer cells, improving the flow of blood through arteries, eliminating brain plaques in Alzheimer's disease, beefing up immunity, reducing inflammation, thwarting blood clots, reducing fractures, preventing arterial blockages from breaking off and causing heart attacks or strokes, and snuffing out free-radical damage.

This broad range of metabolic activity even surpasses that of aspirin. Initially marketed in 1899 as a pain reliever, aspirin over time was found to have a role in reducing the risk of heart attacks, strokes, arthritis, inflammation and colon cancer.

The first statin, Mevacor, was marketed in 1987, but doctors were nervous about prescribing it, fearing side effects. Those fears evaporated by the mid-'90s after several studies showed that statins reduced the risk of heart attacks and were relatively safe. The floodgates opened, and physicians now write about 150 million statin prescriptions annually.

Studies indicate that statins pose no cancer risk and that side effects are minimal. Doctors check patients for elevated liver enzymes, but not one case of liver damage has been tied to statins. Serious side effects causing muscle damage and kidney failure occur in about one in a million users. Muscle aches are the most common complaint, affecting about 1 in 100 people. Liver and muscle side effects are reversible when the drugs are discontinued or the dose lowered.

"The most serious side effect from statins is on par or even less than a serious bleeding side effect of aspirin," Sorrentino said.

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