A handle on heart disease?
The cholesterol drug did absolutely everything it was supposed to do -- except for demonstrably improving the health of the people who took it.

That was the conclusion reached about the popular drug Vytorin in a study published online last week in the New England Journal of Medicine.

The results were a disappointment to the millions of patients who take Vytorin and the thousands of doctors who prescribe it; a blow to its manufacturers, Merck & Co. and Schering-Plough Corp., both of New Jersey; and a surprise to many researchers -- though not all.

The study has raised questions, not only about this particular drug, but about the broader issue of how to treat and prevent heart disease. Here are the answers to some of them.

What is Vytorin?

Vytorin is a combination of two other cholesterol drugs: Zocor, a statin, and Zetia, a non-statin.

Statins work by limiting the amount of cholesterol produced in the liver. They are the only drugs that have been proven to reduce the risk of bad coronary outcomes ( heart attacks, strokes and death).

Zetia works by blocking the absorption of cholesterol from food.

"Vytorin creates a one-two punch," says Dr. Robert Bonow, chief of the cardiology division at Northwestern University and a past president of the American Heart Assn. "It blocks production and absorption."

Why mess with success? Aren't statins good enough?

Statins can have unpleasant, even dangerous side effects, including muscle pain and liver problems. Not everyone can take them. Besides, statins don't always succeed in getting cholesterol levels down to desired levels.

What are the desired cholesterol levels?

They vary from patient to patient. Guidelines issued by the National Cholesterol Education Program are endorsed by the American College of Cardiology, the American Heart Assn. and the National Heart, Lung, and Blood Institute and are widely followed by doctors.

But an editorial in the American Family Physician last year argued that these guidelines are "expensive but not necessarily effective."

The editorial cites a 2006 study in the journal BMJ that compared guidelines in six countries. The cholesterol education program's guidelines lead to treating twice as many patients as New Zealand's guidelines (which were deemed most efficient) without improving mortality rates.

"They have us all on statins," says one of its authors, Dr. Jerome Hoffman, professor of medicine and emergency medicine at UCLA.

What exactly happened in the new study?

The study -- called the Enhance trial -- compared Vytorin to Zocor alone. Vytorin did better at lowering the levels of three undesirables: LDL cholesterol (the so-called "bad cholesterol"), triglycerides and C-reactive proteins.

But researchers found no evidence that it did any better at lowering the big kahuna of undesirables: the risk of bad coronary outcomes.