Vytorin, Zetia should be drugs of last resort, panel urges

CHICAGO -- The blockbuster drugs Vytorin and Zetia should be used only after all other cholesterol-lowering drugs fail until research proves that the medications work, a panel of heart specialists recommended here Sunday.

Shares of Merck mrk and Schering-Plough sgp, the companies market Vytorin, plunged Monday to their lowest levels in years on the news.

The panel, convened by the American College of Cardiology, based its assessment on detailed evidence from a controversial study, released Sunday, showing that Vytorin worked no better than a statin drug now sold as a cheap generic.

"There is absolutely no difference … between the two treatment groups," said lead investigator John Kastelein of the Academic Medical Center in Amsterdam at the group's annual scientific session.

The panel's spokesman, Harlan Krumholz of Yale University, said: "Our strongest recommendation is that people need to go back to statins. … If you were put on this drug before you were fully treated on a statin, you should go back."

The study's results also were released online in the New England Journal of Medicine. The journal's editor, Jeffrey Drazen, and three colleagues offered similar guidance in an editorial.

Both Zetia and Vytorin are made up of a drug, ezetimibe, that blocks the absorption of bad cholesterol, LDL, in the gut. Vytorin also contains the cholesterol-lowering drug simvastatin. Statins block LDL synthesis in the liver.

Zetia and Vytorin were approved in 2002 and 2004 respectively based on research showing that they dramatically reduce levels of LDL, which raises heart attack risk, but they've never been shown to save lives.

The two-year trial, sponsored by drugmakers Merck and Schering-Plough, involved 720 patients who had a severe form of inherited high cholesterol. Half were given simvastatin, also sold as Zocor, and a placebo. The rest were treated with the combo sold as Vytorin.

Researchers compared the drugs' performance by measuring fatty deposits in the carotid arteries that supply the brain and femoral arteries in the legs. They found no differences between patients who took simvastatin alone and those who took Vytorin.

"It was a disastrous outcome for this drug," says Robert Califf of Duke University, co-leader of an 18,000-patient trial called Improve-It, which will be the first to measure whether ezetimibe prevents heart attacks and deaths. The results are due in 2011.

Enrico Veltri, a Schering-Plough vice president, said the trial in "no way changes LDL as a primary target of cholesterol therapy based on medical guidelines. We need to have treatment options available."

In a second study in the New England Journal, Krumholz and his co-workers examined prescribing practices in the USA, where a $200-million-a-year consumer advertising campaign helped build Vytorin and Zetia into blockbusters, and Canada, where direct-to-consumer advertising is banned.

The promotion effort helped the drug capture 15% of the market for cholesterol-lowering drugs vs. 3% in Canada, the study found.