Are Statins Right for You?

They're great at lowering cholesterol levels and have saved the lives of countless heart patients. Now doctors consider whether to expand their use

Ask any three otherwise healthy cardiologists whether they are taking a cholesterol-lowering drug, and chances are good that at least two of them will reply with a hearty "You bet." Their prescription of choice: one of a group of drugs called statins--marketed under such names as Lipitor, Pravachol and Zocor--that have been proved to reduce deaths among heart-attack survivors by more than 40% over five years. In effect, the doctors are taking a highly educated gamble that the medications, currently taken by more than 10 million Americans, will be just as effective in those who do not necessarily fit the profile of a typical high-risk patient.

Such folks often fall through the cracks. Maybe their LDL, or "bad" cholesterol, is a wee bit high, and their HDL, or "good" cholesterol, is a tad low. Or maybe they have diabetes, which commonly leads to cardiovascular disease, but don't yet show the effects. "I'm not recommending putting [statins] in the drinking water," says Dr. Antonio Gotto, a cardiologist and dean of Weill-Cornell School of Medicine in New York City. "But some 6 million to 7 million more people could benefit from their use."

It's an idea that's sure to generate lively debate in New Orleans later this month at the annual meeting of the American Heart Association. Just two weeks ago, a study in the British Medical Journal concluded that statins could reduce the risk of dying from a heart attack 30% even among those with normal cholesterol levels and no sign of cardiovascular disease. Pharmaceutical giants Merck and Bristol-Myers Squibb have gone so far as to petition the Food and Drug Administration to allow consumers to buy some low-dose statins over the counter, without first having to obtain a physician's prescription (more on that below).

So what's the catch? Well, apart from the fact that the drugs are expensive, averaging $3 a pill, and you would presumably have to take them for the rest of your life, they can, in rare cases, cause liver damage or a breakdown of muscle tissue. Anyone who is using statins needs to undergo periodic blood tests to check for signs of liver trouble. Most people on the pills report no complaints; those who do commonly list fatigue as the major side effect. Others refer to the peace of mind statins give them. "I feel safer," says Janet Brown, a 57-year-old New Yorker, who has watched her LDL drop from 177 mg/dl to 90 mg/dl. "I'm not walking on life's tightrope when it comes to my cholesterol."

Statins work by partly blocking an enzyme found in the liver that turns some of the foods you eat into cholesterol. (We couldn't live without some cholesterol; the body uses it to stabilize cell membranes and to manufacture many hormones.) To make up the shortfall, the body draws on the excess cholesterol found in the blood.

By adopting a low-fat diet, getting plenty of exercise and losing a little weight, most people can reduce their total cholesterol levels an average of 10% to 20%. Yet that's only about half the effect of the weakest of the currently available statins. Stronger drugs, like Pfizer's Lipitor, can lop off 50%, and AstraZeneca is testing a "superstatin" that reportedly reduces cholesterol levels as much as 70%. (In each case, statins work best when a low-fat diet is adopted.)

Although the first statins were approved in the U.S. in 1987, they didn't really take off until 1994, when researchers in Scandinavia proved that simvastatin (brand name Zocor) could significantly decrease a heart patient's risk of dying from a second heart attack. After investigators showed that both simvastatin and pravastatin (Pravachol) could cut the number of first heart attacks among those with high cholesterol, doctors assumed that all statins could do likewise.

Their next question had even wider implications: Could statins decrease the risk of heart attack in people with "normal" cholesterol levels and no history of heart disease? But here researchers ran into an ethical dilemma. Considering everything they knew about the effectiveness of statins, would it be fair in a test of their theory to withhold the drugs from those who might benefit from them but would be given a placebo, or dummy pill?

Meanwhile, the dietary-supplement industry got into the act after it discovered that Chinese red yeast fermented on rice contains small amounts of the same active ingredient found in lovastatin (Mevacor). The FDA tried to ban the supplement's sale in the U.S., but the action has become the subject of a lengthy court process. The controversy hasn't stopped Merck, which manufactures Mevacor and Zocor, and Bristol-Myers Squibb, which produces Pravachol, from arguing that they should be allowed to sell their pharmaceutical-grade products at similarly low doses to the general public.

The companies did propose certain restrictions. Even with over-the-counter approval, statins would not be available on drugstore shelves next to cold medications and aspirin. A patient would have to produce a blood test for a pharmacist showing that his or her cholesterol levels met whatever the eventual criteria would be for moderately high levels. Only the pharmacist would be able to review that test and dispense the drug. But a panel of experts was unconvinced, and advised the fda last summer to deny the petition, at least until further studies are completed.

And so things now stand. In the absence of new clinical trials, the researchers who reported in the British Medical Journal used complex mathematical analyses of four previous studies to conclude that statins can reduce the risk of suffering a heart attack even in men and women with normal cholesterol levels and no signs of heart disease. Since this population is fairly healthy, however, doctors might need to treat 250 or more people to save a single life. A bargain for the one whose life is spared, but not so great for the majority, who would not only bear the expense but would also be exposed to potential side effects from a treatment that might turn out to have been unnecessary.

So for the time being, doctors consider the following individuals to be potential candidates for treatment with statins: those whose LDL is 190 mg/dl or higher; those whose LDL is 160 mg/dl or higher and who have at least two risk factors for heart disease, such as smoking, diabetes or high blood pressure; and those whose LDL is 130 mg/dl or higher and who suffer from heart disease.

Many questions remain unanswered. Researchers have shown, for example, that taking an aspirin a day can reduce a heart patient's risk of suffering a heart attack. Would combining aspirin with a statin have a synergistic effect, or is one better than the other in preventing heart disease? Similarly, many cardiologists are impressed by the ability of another group of drugs, called ACE inhibitors, to normalize high blood pressure and reduce the strain on the heart. Would they work better alone or in combination with other drugs?

Dr. Sidney Smith, director of the center for cardiovascular disease at the University of North Carolina in Chapel Hill, predicts that doctors will be much more aggressive in their use of such preventive strategies in the next year or two. "Statins are one therapy; ACE inhibitors are another," he says. "There are pretty powerful data that medical therapy can arrest the progression of coronary disease and atherosclerosis and cut down on cardiac events." As always, the art of medicine is in taking that information and figuring out who will benefit most.

--Reported by Alice Park/New York

VITAL SIGNS

How much your cholesterol can dip

Diet and exercise     10%-20%

Pravachol             20%-30%

Mevacor               20%-30%

Baycol                20%-30%

Zocor                 40%-50%

Lipitor               40%-50%

-PICT-

-ENCH- AS