Cholesterol-lowering medications have been around for decades. Until quite recently those most commonly used included nicotinic acid (niacin), cholestyramine and colestipol hydrochloride, and fibrates such as gemfibozil. Although these drugs can help lower cholesterol quite effectively, they have proven problematic for other reasons. Some studies have indicated that people who take them raise their likelihood of dying of cancer or other ailments that have nothing to do with heart disease. And then there are the side effects: Fibrates, for example, can cause gallstones. Cholestyramine has been linked to embarrassing symptoms such as constipation, flatulence, and upset stomach. And niacin has been shown to cause flushing, hot flashes, and itching.

Troubling reactions like these are all too familiar to Charles Russell, a retired restaurant equipment businessman from Duarte, California. Clogged arteries led to two coronary bypass surgeries, in 1982 and 1992. After the first operation his cholesterol level was 280; he was already on a strict low-fat diet, so his doctor started him on niacin. Russell has unpleasant memories of that time. "I had an itchy feeling on my skin and was constantly blushing," he says. He began having chest pains at night, even though physicians saw no overt heart problems. When his doctor stopped prescribing the niacin, all of these complaints disappeared.

His physician put him on lovastatin instead. The drug helped lower his cholesterol from 330 to 201, but the symptoms of his atherosclerosis had already returned. "I could tell when my arteries were congested because I couldn't breathe very well," he says. After the second bypass Russell switched to atorvastatin. He could feel the difference. "Now my breathing seems quite good. We go skiing at 12,000 feet and I can breathe well -- no chest pain or anything," he says. He exercises three times a week, bicycling and weight lifting. Russell says his cholesterol level has remained comfortably near 150 for more than five years.

Atorvastatin and lovastatin belong to a family of drugs commonly called statins, which are revolutionizing the treatment and prevention of heart disease. (Your doctor may known them as HMG-COA reductase inhibitors.) They appear to work by stabilizing pockets of atherosclerotic plaques, and have proven effective at lowering cholesterol levels in a surprisingly wide spectrum of patients.

That efficiency, combined with fewer side effects than many drugs, is encouraging physicians to treat high cholesterol much more aggressively than they have in the past, both in patients who already have heart disease and in those who are simply at risk of developing it. Upwards of 10 million Americans are now thought to be on statins. Some experts say millions of people who aren't currently taking the pills should be. Indeed, the latest National Cholesterol Education Program guidelines are expected to triple the number of Americans being treated for high cholesterol through drugs, from 13 million to about 36 million. (Not that lifestyle changes are neglected: the number of Americans treated with dietary therapy is expected to rise from 52 million to 65 million.) In some cases, combined drug therapies (statins plus other drugs) may be necessary.

The first statins hit the market in 1987 but didn't burst into the spotlight until 1994, when a landmark study offered the first definitive proof they could lengthen the lives of people with heart disease. Over a six-year period researchers in the Scandinavian Simvastatin Survival Study group tracked more than 4,000 patients who had either survived a heart attack or been treated for angina. During that span the probability that patients taking simvastatin would die from heart disease was reduced 42 percent, while the number who had major cardiac events such as heart attacks dropped 34 percent.

Similar trials of other statins followed in rapid succession. Pooled data from four studies of pravastatin on patients suffering from heart disease, for example, showed a 62 percent reduction in the risk of heart attack. The speed with which the drugs exerted their effects in these trials was remarkable, says Jon Kobashigawa, medical director of the heart transplant unit at the University of California Medical Center in Los Angeles. In the much earlier Coronary Drug Project, which tested niacin against a placebo, it took 15 years for the drug's inability to combat heart disease to appear. "Now, with the statins, the benefits become apparent as early as six months and statistically significant as early as two years," Kobashigawa says. "Something important is happening."

Another study tested pravastatin on patients who had heart disease and moderate cholesterol levels. Once again researchers found the drug delivered measurable benefit. Coronary angiograms showed that pravastatin slowed the progression of atherosclerosis, and the drug reduced the risk of heart attack by 60 percent.

As the success stories rolled in, researchers began testing the statins on a broader range of patients. Could the drugs help heart patient with relatively normal levels of cholesterol? According to results of the 1996 Cholesterol and Recurrent Events trial, the answer was yes. In that study physicians gave pravastatin to more than 2,000 heart attack survivors whose total cholesterol counts averaged only 209, typical of the US population. Patients with such readings account for an estimated 5 million of the nation's 7 million heart attack survivors.

The results were dramatic. Men who received the statin were 20 percent less likely to die from heart disease or to suffer another heart attack than men who took a placebo. For women, the risk fell 46 percent. The drug also cut the risk of stroke by 31 percent. "The message is that if you have a high risk of heart attack, your exact level of cholesterol may not be that important," says Terje R. Peerson, head of cardiology at Aker Hospital in Oslo, Norway. "Whatever it is, it's probably too high."

Researchers cast a wider net, turning their attention to people with high cholesterol who'd never had heart disease. Could drugs protect these patients from a first heart attack? First timers constitute roughly 650,000 of the 1.2 million heart attacks that occur in the United States each year. With that sobering fact in mind, the West of Scotland Coronary Prevention Study enrolled 6,595 men between the ages of 45 to 64 who had never had an attack. The men had an average total cholesterol of 272 and an LDL of at least 155. Patients with these borderline-high LDL levels are not usually treated with drugs.

The study results suggest that perhaps some should be. After five years the men receiving pravastatin averaged a 20 percent reduction in total cholesterol and a 26 percent decrease in LDL. The men who took the drug also had fewer cardiac procedrus such as coronary angiography, bypass surgery, and balloon angioplasty. More important, their risk of a fatal heart attack dropped 31 percent. "This was amazing, for patients who have never had established heart disease, that you could decrease deaths," says Kobashigawa.

The flurry of statin studies continued. One of the most surprising results to date was reported in late 1997: The drugs appeared to benefit patients with relatively normal cholesterol levels and no history of heart disease. The Air Force/Texas Coronary Atherosclerosis Prevention Study tracked 6,605 patients of both sexes and various ethnic groups over five years. The participants -- who had an average total cholesterol of 221, an LDL of 150, and an HDL of 37 -- had never shown any signs of heart disease. Though most physicians wouldn't consider these subjects at high risk of heart disease, a statin produced some eye-opening preliminary data. Men who received lovastatin had a 34 percent lower risk of a first major acute "coronary event" such as unstable angina, fatal or nonfatal heart attack, or sudden cardiac death. The drug cut women's risk 54 percent.

The researchers weren't shy about announcing their conclusions. "The results of the study carry profound implications for many adults who think they are at low risk of a heart attack," says Antonio M. Gotto, Jr., dean of Cornell University Medical College in New York City and lead author of the study. He says the findings reaffirm the need for patients to have their LDL and HDL levels checked regularly. "Even if their LDL is considered average, they may still be at risk for a heart attack if their HDL is too low."

However, like all medications, the drugs are not risk-free. The statin Baycol (cerivastatin) was withdrawn from the US market in August 2001 after the Food and Drug Administration logged 31 reports of deaths linked to a muscle-wasting illness associated with the drug. The manufacturer, Bayer, advises doctors to switch all patients taking Baycol to another cholesterol-lowering drug. And if you're a patient who experiences fever, vomiting, dark urine, and muscle pain, weakness, or tenderness, stop taking the drug immediately and get medical help.

Part III: How much is too much?

First published May 21, 2001
Last updated September 17, 2007
Copyright © 2001 Consumer Health Interactive