Warnings: Vytorin/Zetia

In case you hadn't heard of this previously, from Google today: 

CHICAGO — Two widely prescribed cholesterol-lowering drugs, Vytorin and Zetia, may not work and should be used only as a last resort, The New England Journal of Medicine said in an editorial published on Sunday.

The journal’s conclusion came as doctors at a major cardiology conference in Chicago saw for the first time the full results of a two-year clinical trial that showed that the drugs failed to slow, and might have even sped up, the growth of fatty plaques in the arteries. Growth of those plaques is closely correlated with heart attacks and strokes.

Merck and Schering-Plough, the companies that make Vytorin and Zetia, said on Sunday that despite the results of the trial, they would continue to promote their medicines as first-line treatments for high cholesterol.

The medicines are among the top-selling drugs in the world, with total sales of about $5 billion last year. About four million Americans take them.

But some scientists, including many of the same doctors who criticized Merck over the arthritis drug Vioxx and were eventually proved correct about Vioxx’s risks, say the companies are overstating the evidence of the drugs’ effectiveness and that doctors should not prescribe the drugs.

At the moment, no evidence exists to show that Vytorin and Zetia help patients, said Dr. Harlan Krumholz, a cardiologist at Yale University.

The drugs could even be harmful, Dr. Krumholz said. He spoke on a panel on Sunday discussing the trial at the American College of Cardiology annual conference in Chicago.

“Just because you know what a drug does to cholesterol doesn’t mean you know what it does to patients,” Dr. Krumholz said.

The stakes of the debate are high both medically and economically. About five million people worldwide take Vytorin and Zetia, mostly in the United States, where the drugs have been most heavily marketed. They are the major contributor to Schering-Plough’s profit.

Unlike other cholesterol medicines, called statins, which block the liver from making cholesterol, Zetia works by blocking the intestine from absorbing cholesterol in food. Vytorin is a single pill that combines Zetia with a statin called Zocor.

LDL cholesterol, the harmful kind, is known as a risk factor for heart disease, and so doctors have generally assumed that lowering LDL cholesterol would reduce the risk of heart attacks and strokes.

But proving that a drug actually cuts those risks requires an expensive, multiyear clinical trial enrolling 10,000 or more patients. Those studies, called outcomes trials, have been conducted for statins like Lipitor and Zocor, and they have proved that patients taking those drugs do have a reduced risk of heart disease. No such outcomes trials exist for Vytorin and Zetia.

In 2006, four years after Zetia reached the market, Merck and Schering began enrolling patients in their own outcomes study, which compares people taking Vytorin to those taking Zocor alone.

But the companies said Friday that the results of the trial, which had been expected in 2011, would not be available until 2012, and possibly later.

As a result, doctors who prescribe the medicines are doing so without hard evidence that they help patients, said Dr. Steven Nissen, chairman of cardiology at the Cleveland Clinic.

“We’ve got a drug that has no clinical outcome trials,” Dr. Nissen said. “I