CHICAGO — Full results of a failed trial on Vytorin, a medicine taken by millions of Americans to lower cholesterol, left doctors stunned that the drug did not improve heart disease even though it worked as intended to lower three key risk factors.

Use of Vytorin and a related drug, Zetia, seemed sure to continue to fall after the findings reported Sunday and fresh questions about why drugmakers took nearly two years after the study ended to give results.

"A lot of us thought that there would be some glimmer of benefit," said Dr. Roger Blumenthal, a Johns Hopkins University cardiologist and spokesman for the American Heart Association.

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," Blumenthal said.

Doctors have long focused on lowering LDL or bad cholesterol as a way to prevent heart disease. Statins like 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 super high 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 journal 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 discontinue using it or any heart drug without talking with their doctors, heart specialists stressed.

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 — ten 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.

Dr. James Stein, director of preventive cardiology at the University of Wisconsin-Madison, said Vytorin "has always been a second- or third-line drug," after trying statins and other recommended medicines first.

Stein believes Zetia and Vytorin are safe and will prove effective, "but the reason we do research us so we don't have to rely on our "beliefs" — we can rely on data."

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