Study raises more doubts about cholesterol drugs Zetia, Vytorin

A widely prescribed and expensive cholesterol drug does not unclog arteries as effectively as a modified version of Vitamin B3, a cheap alternative used to treat heart disease for decades, according to a new study.

The research, which appears today in the New England Journal of Medicine, is the third recent study to raise questions about the effectiveness of Zetia and Vytorin, highly profitable medications by Merck.

"This is the third strike," said Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic in Ohio. "The studies are telling us that it doesn't appear to produce benefits. This is a drug used by millions of Americans, a very big seller, in a health-care system where costs are a major issue. And the question has to be, is this the right approach?"

Last year, U.S. physicians wrote more than 29 million prescriptions for both Vytorin and Zetia, and worldwide sales totaled $4.56 billion, according to Merck.

Although the drugs have been shown to reduce cholesterol, there is no evidence they prevent heart attacks or strokes.

Top Merck executives have dismissed the new research as limited.

"I don't think a clinician or a doctor or a patient should use this as the basis for any decision-making whatsoever," said Richard Pasternak, vice president of Merck research laboratories.

Critics said today's study involved just 200 patients, was ended early and examined the amount of plaque on artery walls rather than evaluating the rate of heart attacks and stroke.

Because plaque can clog arteries and restrict blood flow, cardiologists view it as a good indication for the risk of heart attack and stroke.

Introduced in 2002 and 2004, Zetia and Vytorin became blockbusters for Merck and Schering-Plough. But new research has placed the drugs under greater scrutiny and the number of written prescriptions has slipped.

Last year, a study released by Merck showed Zetia did not reduce plaque in arteries when compared with patients taking only statins, which are available in generic form. Although released in January, the study had been completed in 2006, prompting a class-action that claimed Merck intentionally withheld unfavorable results. Merck paid $41.5 million to settle the claims.

Another study published last year showed a potential increase in cancer among patients taking Zetia and Vytorin, compared with those taking only statins.

Taken as a whole, the new research is unnerving, said Harlan Krumholz, a Yale University cardiologist.

Statins, such as Lipitor, have been used to lower cholesterol by inhibiting the production of LDL, low-density lipoprotein often called "bad" cholesterol, which can lead to plaque buildup.

Zetia uses a different mechanism. It blocks the absorption of cholesterol from food in the intestines.

Vytorin is Zetia combined with a statin in one pill.

The study released today followed about 200 patients taking statins. Some were also given Niaspan, a modified form of vitamin B, or niacin. The rest took Zetia.

The patients who took Niaspan had less plaque in their arteries and also had higher levels of high-density lipoprotein or HDL, known as "good" cholesterol.

The patients who took Zetia had more plaque but lower levels of LDL. They also had more heart attacks, strokes and other cardiovascular problems than the patients taking niacin.