_____From The Post_____ • Tastes Great, Less Killing (The Washington Post, Jul 24, 2001) • What You Eat May Alter Your Age (The Washington Post, Jun 20, 2001) • You and A.: The New Cholesterol Guidelines, Explained (The Washington Post, May 22, 2001) • A Heart Drug Far Surpasses Expectations (The Washington Post, May 19, 2001) • NIH Revises Guidelines on Cholesterol (The Washington Post, May 16, 2001) • Cholesterol Remedy Loses Round (The Washington Post, Jul 14, 2000) _____More on Statins_____ • Should You Take Statins? • On the Web: American Family Physician on Statins • On the Web: Can Statins Prevent Strokes? E-Mail This Article Printer-Friendly Version Subscribe to The Post

By Francesca Lunzer Kritz
Special to The Washington Post
Tuesday, July 31, 2001; Page HE06

New guidelines issued recently by the federal government's National Cholesterol Education Program (NCEP) could triple the number of Americans taking a class of prescription drugs called statins, bringing the total to 36 million people. This means as many as one in six American adults could be advised to take the drugs.

The expert panel that wrote the guidelines hopes that expanded use of the drugs -- together with improved diets and more exercise -- will help reduce the close to 1.1 million heart attacks and half a million deaths attributed to heart disease each year. The major aim is reducing LDL cholesterol, the so-called bad cholesterol, especially in people with heart disease, diabetes or multiple risk factors for a heart attack. The target LDL for these high-risk people is 100 milligrams per deciliter or less; for those with two or more risk factors, the ceiling is 130.

Individuals with moderately higher LDL levels and only one or no risk factors may get a three-month grace period to try to bring down their number with diet and exercise alone. But if that effort fails, or either your readings or your risk factors mount, expect to be advised to start drug therapy. Your doctor may also base his recommendation on your risk of having of a heart attack in the next 10 years.

Statin drugs, generally the first-line pharmacological defense against high cholesterol, work by slowing down the liver's production of cholesterol and increasing that organ's ability to remove LDL cholesterol already in the blood. Statins may also modestly increase HDL, the good cholesterol, and slightly decrease triglycerides, another fat in the blood.

Statins are already a growth market for pharmaceutical companies. Last year they brought in the most revenue of any class of drugs, with U.S. sales of $9 billion, according to IMS Health, a drug research firm. Of the six statin drugs sold in the United States, three dominate: Lipitor, which claims about half the statin market; Zocor, which has about a third; and Pravachol, which enjoys much of the rest.

For patients needing no more than a 20 percent reduction in cholesterol levels, it's likely that any of the statins will be equally effective, said James Howard, medical director of the Washington Hospital Center and a member of the NCEP's guidelines panel. Genaissance Pharmaceuticals, a New Haven, Conn., company, has just completed enrollment in a clinical trial that will use genetic markers to match patients to the statin drug and dose most likely to be effective. For now, in the absence of other individual factors, observers say journal studies and drug promotions likely influence doctors' choices and help drive prescription volume.

But for patients with more elevated cholesterol levels, doctors may be more likely to prescribe some of the newer, more potent statins, which, particularly at higher doses, can produce a steeper drop. Lipitor, for example, has been shown to reduce as much as 60 percent of LDL cholesterol at the highest doses (80 mg). If further reduction is needed, physicians often add a second or third drug from a different class of cholesterol-lowering drugs.

But if some recent, preliminary studies prove correct, Lipitor at the highest doses may have an undesired effect: it may not work as well as Zocor in raising HDL, the so-called good cholesterol. Doctors say they will be watching additional studies addressing this question.

Statins, on the market since 1987, have a solid safety record. The most common side effects are gastrointestinal, including gas, nausea and upset stomach.

"With most drugs used over several years, we'd expect to see a few new side effects, but that hasn't been the case with the statin drugs," said Howard. In five separate drug trials that involved a total of 30,000 people each over five years, he said, statin drugs produced no more side effects than placebos.

But some uncommon side effects -- particularly those associated with liver and kidney function -- could be worrisome, and a few potentially serious enough to merit attention.

In one in 100 patients, a statin drug will elevate liver enzymes, an indication that the liver has been irritated. Enzyme elevation is a common side effect of many drugs, including aspirin and acetaminophen, and doesn't necessarily indicate a serious problem, said Nilo Cater, assistant professor of medicine at the University of Texas Southwestern Medical Center at Dallas. But because it can pose a risk, blood tests for liver enzymes are standard procedure for anyone on statin drugs. Your doctor should check your liver enzymes before you start a statin drug, and then a few weeks later and a few weeks after any dose increase. Once you're maintained on a dose, you should have your liver enzymes checked at least twice a year, said Howard.

In one in 1,000 patients, statin drugs may cause muscle weakness. If weakened muscles start to break down, they can release an enzyme, creatine kinase, that in very rare cases can lead to severe kidney damage, said Cater. Any patient complaint of muscle weakness should be followed by a blood test. Results of the test will help your doctor decide whether to keep you on the same statin, switch to another brand or choose a different class of drug.

Because drug interactions with statins can raise the risk of liver, kidney or muscle-weakness problems, it's important to tell your physician about every prescription, over-the-counter and herbal product you take. Some antifungal drugs, certain antibiotics and even some other cholesterol-lowering drugs may interact with statins. All statins except Pravachol may interact with large quantities of grapefruit juice.

Pravachol may offer the lowest risk of drug interaction and is often the favorite choice of physicians concerned about drug interactions, according to both Howard and Noel Barrie Merz, head of the American College of Cardiology's committee on preventive cardiology and a cardiologist at Cedars-Sinai Hospital in Los Angeles.

The cost of the statin drugs can vary considerably, from a low of about $44 per month for the starting dose of Lescol (purchased through drugstore.com) to about $63 for the starting dose of Zocor. Lipitor and Zocor are among the six most expensive drugs prescribed for older Americans, many of whom don't have prescription drug coverage, according to a recent report from Families USA, a health advocacy group. The price of both drugs increased at more than three times the inflation rate between January 2000 and January 2001, according to the report. Because these are such high-ticket drugs, some insurers set a co-pay as high as $40 per prescription. The best co-pay-reducing strategy may be to ask your doctor to prescribe a three-month supply.

While people whose insurance includes drug benefits will usually have statin drugs covered, insurers may have struck a deal with a particular manufacturer, so you may be refused coverage, or given reduced coverage, for the brand your doctor has recommended. You'll want to bring any rejection to your doctor's attention. Howard said he can often get coverage for his patients by explaining to the insurer why he chose the particular drug.

Next year should bring some cost savings. Mevacor, an older statin, will lose its patent protection, and generic versions could cost as little as $42 for a 30-day supply of the starting dose when they first hit the market, and $25 a few months later, based on generic drug pricing history. But the expected entry of AstraZeneca's Crestor, a statin that may have more cholesterol-lowering power than any other yet, won't cool the brand-name market.

While statin drugs are the hands-down favorites for lowering LDL cholesterol, there are alternatives. Patients with high triglycerides, those who can't tolerate statins and some who need to lower cholesterol more than a statin does may get a prescription for nicotinic acid (niacin), a bile acid sequestrant or a fibrate drug.

Niacin, effective both for raising HDL and lowering triclycerides, is available over-the-counter, but a prescription version, Niaspan, reduces the likelihood of liver toxicity, itching and flushing of the skin. Just last week, the FDA gave preliminary approval to a Niaspan/lovastatin combination pill, Advicor, which could be available by next summer. Bile acid sequestrants, which bind with cholesterol-containing bile acids and then are eliminated in the stool, may be added to a statin regimen to enhance LDL reduction. Fibrates, effective in lowering triglycerides and raising HDL, may produce mild gastrointestinal upset.

Like diamonds, statins are forever. Once your doctor determines you need medication to lower cholesterol, you will likely be filling a prescription for the rest of your life.

That can be a challenge, said Dan Albrant, president of Pharmacy Dynamics in Arlington and a hospital pharmacy consultant, since patients with high cholesterol typically don't feel ill and so may find it hard to stick to a drug regimen that doesn't provide any noticeable benefits. In addition, many physicians leave their patients at a statin's starting dose, which is often inadequate to reach the 35 percent LDL reduction the typical statin patient needs.

Cater said statin patients should see their doctors at least twice a year to have their doses evaluated.

Increasingly, statin patients may have more incentive to stay on the drugs -- and on the right dose. Evidence shows the drugs not only reduce cholesterol but may help prevent heart attacks and strokes, curb the risk of Alzheimer's and diabetes, lower the rate of organ rejection in some transplants and even protect against cancer.