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Why You May Need Cholesterol Drugs

Even adults at moderate risk for developing heart disease can benefit from these medicines.

You're healthy, you're pretty thin, or at least not overweight, and you never thought your cholesterol was particularly high. Yet your doctor says you should consider taking a cholesterol-lowering drug.

Welcome to a big and fast-growing club. Twenty million Americans take cholesterol-lowering drugs, making them the most frequently prescribed drugs in the country. The vast bulk of them take statins such as Zocor, Lipitor or Crestor.

There's a reason for the popularity: Statins have been proven again and again in big clinical trials to prevent heart attacks and strokes. When patients at risk for heart disease are prescribed either a statin or a sugar pill, the ones who get the statin are less likely to die or suffer heart attacks. The drugs appear to work even in patients who don't have high cholesterol, but are at risk for cardiovascular disease for other reasons.

Click here for a list of the most popular cholesterol drugs.

"These drugs save lives," says James Stein, director of preventative cardiology at the University of Wisconsin. "You'd be hard pressed to find a class of drugs with more evidence for how safe and effective they are. The risk-benefit ratio trumps almost any other medication I can think of."

But be warned: Not all cholesterol-lowering drugs are created equal. Merck's ( MRK - news - people ) popular drug Zetia works very differently from statins. In sharp contrast to statins, there are no big trials showing that Zetia prevents heart attacks. For this reason, Henry Ford Hospital cardiologist Douglas Weaver advises using it only as "a last resort" in people who cannot get their cholesterol under control with other drugs. Others disagree, saying the most important thing is to get cholesterol down.

Diet and exercise lower levels of bad cholesterol, but you'll probably have to make radical lifestyle changes to have a big impact. Federal guidelines recommend that doctors should base a decision to start cholesterol drugs on a person's overall heart disease risk, not merely what the cholesterol numbers are. Besides cholesterol, risk factors for heart disease include advancing age, diabetes, high blood pressure, cigarette smoking, and family history of heart disease.

Some cholesterol is necessary for the body to make cell membranes and some hormones like testosterone and estrogen. But once you get above the relatively low level that was seen in hunter-gatherers, you are at risk for artery disease. Even the pharaohs of ancient Egypt had atherosclerosis.

Excess cholesterol accumulates in the arteries as a buttery, waxy gunk. It causes the artery wall to become inflamed. Over time, scar tissue accumulates over the waxy gunk to form plaques. Occasionally, one of these plaques will burst, forming a blood clot that blocks off an artery. If it happens in an artery that leads to the heart or brain, the result is a heart attack or stroke.

Surgery can undo clogs in specific locations, but statin drugs slash atherosclerosis throughout the body. They do so by short-circuiting a process in the liver that creates cholesterol particles that circulate throughout the body. The basic science behind them won the 1985 Nobel Prize in Medicine.

Statins vary in the amount that they lower bad cholesterol levels. Crestor, from AstraZeneca ( AZN - news - people ), and Lipitor, from Pfizer ( PFE - news - people ), are the most potent, but Zocor (simvastatin), Pravachol (pravastatin), and Mevacor (lovastatin) are generic and much cheaper. Patients who cannot tolerate one statin often do fine on another.

Guidelines written by government-selected experts recommend treating patients who don't have established heart disease to get their low-density lipoprotein (LDL), or "bad cholesterol," down to 130 mg/deciliter, with an optional target of 100 mg/dL.

An Oxford University analysis of 14 clinical trials of 90,000 patients showed the odds of dying from heart disease go down 15% for every 40 points that LDL is lowered with a statin. The most recent big study found that patients at moderate risk of heart disease who took high doses of AstraZeneca's Crestor for two years had a 20% lower death rate than those who took a placebo.

Statins have other benefits besides lowering bad cholesterol. They raise levels of good cholesterol and appear to reduce artery inflammation. Even for patients with other types of heart risks, statins may be the most effective way to reduce the risk of a heart attack or stroke, says Oxford University cardiologist Rory Collins.

The major side effect of statins is muscle pain and weakness. In rare cases, the drugs can cause severe muscle breakdown that leads to kidney failure. Baycol, a statin sold by Bayer ( BAY - news - people ), was pulled from the market in 2001 after it was linked to 52 deaths. But the remaining statins appear to have much lower rates of serious muscle-related side effects. If you are on statins and experience widespread muscle weakness, you should call your doctor immediately.

Other pharmaceutical options for lowering cholesterol don't have the same accumulation of evidence behind them. Niacin, which drops LDL and raises HDL, causes unpleasant facial flushing in many patients. Older drugs called resins can cause constipation and require patients to take lots of pills every day.

Merck's newer cholesterol drug Zetia (which together with Zocor forms the combination pill Vytorin) became very popular because it doesn't cause many unpleasant side effects. But two recent trials using ultrasound to look at clogged arteries have raised questions about whether Zetia prevents atherosclerosis. In one such trial in March 2008, Zetia failed to beat a placebo pill. Its popularity is waning.

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