A drug just approved by the Food and Drug Administration offers a new strategy for the estimated 20 million Americans taking cholesterol-lowering drugs.
Zetia, made by Merck/Schering-Plough Pharmaceuticals, received approval late last week to treat cholesterol via a different mechanism than that of cholesterol drugs already on the market. Unlike the widely prescribed statin drugs, which block cholesterol production, Zetia works by preventing the absorption of cholesterol in the intestine.
Because the mechanisms of action are different, Zetia may be used in concert with statin drugs in an effort to drop cholesterol levels still further.
This may be especially important for a number of people taking statin drugs who have not managed to reach their target cholesterol levels.
"Although statins are first-line because we have very good safety and efficacy data, if you take a look in clinical practice, probably only about 40 percent of these high-risk patients are at their target," says Dr. Christie Ballantyne, director of the center for cardiovascular disease prevention at Baylor College of Medicine in Houston, who has conducted research on Zetia.
Risks and Benefits
According to NDS Health, a health-care information services company based in Atlanta, more than 110 million prescriptions were written for statin drugs in 2001.
While favored for their efficacy, these drugs do not come without risk. Possible side effects include muscle and liver damage. Even though the incidence of these side effects is rare, one statin drug, Baycol, was withdrawn from the market after reports of severe and sometimes fatal muscle reactions.
The loss of Baycol has made many physicians more attentive to the possibility of side effects and their patient's concern about safety.
"I have definitely had to increase my discussion of side effects of statin-type cholesterol medications with my patients," says Dr. Scott Smith, a family physician from Kaiser Permanente in Denver. "Many more people are concerned about them."
Some see potential that combining Zetia with statins may decrease the side-effect risk.
"My gestalt is that higher statin dosage increases the possibility of side effects," says Dr. Ramon Parrish, chief of the family practice service at the Emory University School of Medicine in Atlanta. "I would give this a serious look as an alternative."
One study found that combining a 10 milligram dose of Zetia with the starting dose of two of the most popular statins, Lipitor and Zocor, was as effective in reducing "bad" cholesterol as the highest dose of either statin alone.
Yet while Zetia alone or in combination with these statins appeared to be well-tolerated in the 3,000 to 4,000 patients in whom it has been tested, larger trials are needed.
"What we don't have is a big enough study to say that it would really be safer," says Ballantyne. "The statins are awfully good and so you have to do a very big study to compare [high doses] of a statin to a lower dose of a statin with Zetia."
A Hard Sell
For many who treat patients with high cholesterol, the track record of statins alone is enough to prevent them from embracing a combination approach.
"The statins are fantastically effective and have relatively few effects, so the numbers of patients who will need something in addition to a single statin or who don't tolerate moderate to high doses of statins are small," says Dr. Michael Good, a family physician from Middletown, Conn.
The cost of combining the two types of drugs is also a factor.
"These new lipid drugs continue to be expensive," says Dr. Francis Solano Jr., president and chief medical officer of Community Medicine Inc. in Pittsburgh. "Statins can be around $60 to $120 per month."
Still others have concerns about compliance and how well their patients will appreciate taking more than one cholesterol-lowering medication a day.
"It is difficult enough to get us to take the medications we have now, much more difficult to add an extra drug into the mix," says Dr. Bhaswati Bhattacharya, attending physician at Wyckoff Heights Medical Center, New York-Presbyterian Hospital.
So even if a Zetia-statin combo proves safe and effective, getting physicians to prescribe — and patients to take — two drugs instead of one may prove to be a hard sell for many.