Cholesterol drug Vytorin does 'zilch' to help heart disease

CHICAGO -- Leading doctors urged a return to older, tried-and-true treatments for high cholesterol after hearing full results Sunday of a failed trial of Vytorin.

Millions of Americans already take the drug or one of its components, Zetia. But doctors were stunned to learn that Vytorin failed to improve heart disease even though it worked as intended to reduce three key risk factors.

"People need to turn back to statins," said Yale University cardiologist Dr. Harlan Krumholz, referring to Lipitor, Crestor and other widely used brands. "We know that statins are good drugs. We know that they reduce risks."

The study was closely watched because Zetia and Vytorin have racked up $5 billion in sales despite limited proof of benefit.

Two congressional panels launched inquiries into why it took drugmakers nearly two years after the study's completion to release results.

Many doctors were prescribing Vytorin without trying older, proven medications first, as guidelines advise. The key message from the study is "don't do that," said Dr. Roger Blumenthal, a Johns Hopkins University cardiologist and spokesman for the American Heart Association.

Doctors have long focused on lowering LDL, or bad cholesterol, as a way to prevent heart disease. Statins such as Merck & Co.'s Zocor, which recently became available in generic form, do this, as do niacin, fibrates and other medicines.

Vytorin, which came out in 2004, combines Zocor with Schering-Plough Corp.'s Zetia, which came on the market in 2002 and attacks cholesterol in a different way.

The study tested whether Vytorin was better than Zocor alone at limiting plaque buildup in the arteries of 720 people with superhigh cholesterol because of a gene disorder.

The results show the drug had "no result -- zilch. In no subgroup, in no segment, was there any added benefit" in terms of reducing plaque, said Dr. John Kastelein, the Dutch scientist who led the study.

That happened even though Vytorin dramatically lowered LDL, other fats in the blood called triglycerides and a measure of artery inflammation called CRP.

Results were presented at an American College of Cardiology conference in Chicago and published on the Internet by the New England Journal of Medicine.

The New England Journal of Medicine also published a report showing that Vytorin and Zetia's use soared in the United States amid a $200 million marketing blitz. In Canada, where advertising drugs to consumers is not allowed, sales were four times lower.

Congress and state officials in New York have been investigating why results were not released for nearly two years after the study ended.

The drug appeared safe in the study, and patients should not stop using it or any heart drug without talking with their doctors, heart specialists said.

However, doctors prescribing Vytorin in the mistaken belief it always works "should be thinking twice," said Duke University cardiologist Dr. Robert Califf.

He is co-leader of an even more pivotal study of the drug that was expanded to include more patients because early signs suggest it will be harder than anticipated to see if Vytorin is any better than Zocor alone.

Califf himself takes the drug because he cannot tolerate the high dose of statins he otherwise would need.

"It will be 2012 -- 10 years after the drug was introduced -- before we know the answer," said Dr. Steven Nissen, a Cleveland Clinic cardiologist who has no role in the Vytorin studies and has criticized the drugmakers' handling of the one reported Sunday.

Merck is based in Whitehouse Station, N.J.; Schering-Plough, in Kenilworth, N.J.