By Rob Stein
Washington Post Staff Writer
Tuesday, January 15, 2008
A popular cholesterol-lowering drug failed to help slow the buildup of artery-clogging plaque in a long-awaited study, the companies that market the medication said yesterday, raising questions about whether its use should be limited.
The drug, Vytorin (a combination of Zetia and Zocor), also did not reduce the thickness of plaque lining artery walls, a significant disappointment for the manufacturers.
"Obviously, we would have preferred a more favorable result," said Skip Irvine, a spokesman for Merck-Schering-Plough Pharmaceuticals, a joint venture between the two companies that markets both Zetia and Vytorin.
Other experts said the findings mark a major blow for the medications.
"This is stunning," said Steven Nissen, a Cleveland Clinic cardiologist who was not involved in the research. "I do not believe it should be used as a first-line therapy. It should only be used as a last resort. That's a stunning reversal for what was previously one of the fastest-growing cholesterol-lowering medications being used."
The companies disputed Nissen's conclusions, saying the study showed once again that Zetia was highly effective at lowering cholesterol levels. The companies are sponsoring another large study aimed at evaluating the drug's ability to prevent heart attacks and strokes.
"We expect that study to be completed sometime in 2011," Irvine said.
Zetia was approved in 2002, and Vytorin was approved in 2004. Both quickly became popular. Doctors wrote about 18 million prescriptions for Vytorin and about 14 million for Zetia in 2006, making them among the most commonly prescribed cholesterol-lowering drugs, and their popularity has continued to grow, according to IMS Health, a health-care information company.
Previous studies have shown Zetia and Vytorin are effective at lowering cholesterol, but other medications that do this have been shown to have additional benefits, such as slowing the buildup of plaque or sometimes even shrinking it, and reducing the risk of heart attacks and strokes and lowering mortality rates.
The new company-sponsored study was the first attempt to demonstrate Vytorin's ability to slow the progression of heart disease. It involved 720 patients in Europe suffering from a genetic condition that causes high cholesterol levels. About half the patients received Vytorin, and the other half received Zocor alone.
After two years, ultrasound measurements of plaque buildup in neck arteries found no significant difference between the two groups, and even indicated that those receiving Vytorin may have experienced slightly more buildup.
"It failed to slow buildup of plaques," Nissen said. "If anything, the trends were going in the wrong direction -- the patients getting Zetia actually had a little faster plaque buildup compared to those who got generic Zocor."
There were no signs that patients taking Vytorin were any more likely to suffer side effects or heart problems, but Nissen and others said the study suggests that putting patients on the medications denies them the additional benefits of competing drugs such as Lipitor, Zocor, and Crestor.
"Whenever you use an ineffective treatment, it means you are denying them effective treatments," Nissen said.
The companies have come under criticism from cardiologists and members of Congress for failing to release the findings sooner.