Lower Cholesterol

When a patient without heart disease is first diagnosed with elevated blood cholesterol, doctors often prescribe a program of diet, exercise, and weight loss to bring levels down. National Cholesterol Education Program guidelines suggest at least a six-month program of reduced dietary saturated fat and cholesterol, together with physical activity and weight control, as the primary treatment before resorting to drug therapy. Typically, doctors prescribe the Step I/Step II diet to lower dietary fat, especially saturated fat. Many patients respond well to this diet and end up sufficiently reducing blood cholesterol levels. Study data reinforce these benefits.

For example, a 1998 Columbia University study examined 103 male and female patients of diverse ages and ethnic backgrounds and found that reducing dietary saturated fat directly affected blood cholesterol. For every 1 percent drop in saturated fat, the study showed a 1 percent lowering of LDL in patients.

But sometimes diet and exercise alone are not enough to reduce cholesterol to goal levels. Perhaps a patient is genetically predisposed to high blood cholesterol. In these cases, doctors often prescribe drugs. The National Cholesterol Education Program estimates that as many as 9 million Americans take some form of cholesterol-lowering drug therapy. The most prominent cholesterol drugs are in the statin family, an array of powerful treatments that includes Mevacor (lovastatin), Lescol (fluvastatin), Pravachol (pravastatin), Zocor (simvastatin), Baycol (cervastatin), and Lipitor (atorvastatin). Many doctors say statin drugs have revolutionized patient care.

"These drugs have had a fantastic impact on cholesterol treatment," says Redonda Miller, M.D., assistant professor of medicine at Johns Hopkins University School of Medicine. "They all lower cholesterol levels, but the side effects are minimal."

A study published in the medical journal Circulation in 1998 showed that statins dramatically lower the risk of dying from heart disease. Research found that for every 10 percentage points cholesterol was reduced, the risk of death from heart disease dropped by 15 percent.
So far, only three of the drugs--Mevacor, Zocor and Pravachol--have been studied in long-term, controlled trials. "Based on existing evidence, [statin drugs] all have similar safety profiles and are effective at lowering cholesterol in appropriately selected patients," says FDA's Orloff. "The difference between drugs lies mainly in their absolute capacity to lower cholesterol--that is, at the highest approved daily doses."

One landmark study completed in 1994, the Scandinavian Simvastatin Survival Study, or 4S, showed a 42 percent reduction in deaths from heart disease and a 30 percent drop in death from all causes over five years in patients with coronary heart disease whose high LDL levels were lowered with Zocor. The West of Scotland study, reported in 1995, revealed similar benefits from lowering LDL levels with Pravachol in patients without heart disease. And the Cholesterol and Recurrent Events (CARE) study, reported in 1996, showed that lowering LDL levels with Pravachol reduced heart attacks and deaths in patients with a previous heart attack but with cholesterol levels relatively average for the general population. This study showed that Pravachol treatment not only reduced death from heart disease but also death from all causes in a group of heart disease patients with average cholesterol levels.

A 1997 study, the Air Force/Texas Coronary Atherosclerosis Prevention Study, showed that Mevacor helped prevent a first heart attack or unstable angina in men and women with average cholesterol levels but with below-average HDL.

Statins work by interfering with the cholesterol-producing mechanisms of the liver and by increasing the capacity of the liver to remove cholesterol from circulating blood. Statins can lower LDL cholesterol by as much as 60 percent, depending on the drug and dosage.
Heart patient Norbert Hoffmann, 65, of Northfield, Minn., saw what he calls "a dramatic drop" in cholesterol levels after taking Zocor for three months. For example, his total cholesterol went from 270 to 145 mg/dL and LDL from 182 to 82 mg/dL.

But patients can respond differently to drugs. Some patients may have fewer side effects with one drug than another. "I had problems such as stomach cramps with Zocor," says Oklahoma patient Linden Gilbert, 50. His doctor ultimately switched him to Lipitor, which he credits with lowering his total cholesterol from 230 to 150 mg/dL.

Other Drug Treatments
These include:
* Nicotinic acid (niacin)-This lowers total and LDL cholesterol and raises HDL cholesterol. It also can lower triglycerides. Because the dose needed for treatment is about 100 times more than the Recommended Daily Allowance for niacin and thus can potentially be toxic, the drug must be taken under a doctor's care.
*Resins--Doctors have been prescribing Questran (cholestyramine) and Colestid (colestipol) for about 20 years. These "resins" bind bile acids in the intestine and prevent their recycling through the liver. Because the liver needs cholesterol to make bile, it increases its uptake of cholesterol from the blood.
* Fibric acid derivatives--Used mainly to lower triglycerides, Lopid (gemfibrozil) and Tricor (fenofibrate) can also increase HDL levels.
* Aspirin--Because studies have shown that aspirin can have a protective effect against heart attacks in patients with clogged blood vessels, doctors often prescribe the drug to patients with heart disease.

The decision of which drug to prescribe is one the doctor makes based on factors such as degree of cholesterol lowering desired, side effects, and cost. "If a patient has only a modest cholesterol elevation, I might prescribe Mevacor," says Johns Hopkins' Miller. "But if a more drastic reduction is needed, especially of LDL, I'll prescribe Lipitor."

The potential for drug interaction is a crucial concern, says FDA's Orloff. "Some statin drugs are known to interact adversely with other drugs, and that information may guide a decision about which statin to use." In June 1998, FDA announced the withdrawal of the drug Posicor (mibefradil), used to treat high blood pressure and stable angina, because it caused adverse reactions in patients taking various other drugs, including Mevacor and Zocor.

Though it is impossible to know yet just how many lives cholesterol-lowering therapies have saved, public health experts say awareness efforts such as the National Cholesterol Education Program are getting the word out to Americans about heart disease, its prevention and management. Reflecting on his own experience with elevated cholesterol, Hoffmann says, "Get informed [about cholesterol]. Read books, search the Internet, look at your risk factors, and, most of all, don't wait to do something about it if you have a [cholesterol] problem."
John Henkel is a staff writer for FDA Consumer.