Vytorin and its sister drug Zetia

A controversial study showing that the blockbuster cholesterol-lowering drug Vytorin failed to slow the buildup of artery plaques more than a cheaper statin is certain to provoke questions among heart patients taking Vytorin or its sister drug Zetia. USA TODAY asked Steven Nissen, the Cleveland Clinic's chief of cardiology, and Roger Blumenthal of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease and the American College of Cardiologyprevention committee, for some answers.

Q: Why was the study controversial?

A: The two drugs are among the most widely used of all prescription medicines. Yet, although the drugs have been shown to reduce cholesterol, their manufacturers acknowledge that they've never been shown to prevent heart attacks or other life-threatening events. Lipitor and other statin drugs, in contrast, have demonstrated their effectiveness in many studies.

A congressional committee said in December it will investigate allegations that the companies that make the drugs, Merck and Schering-Plough, delayed releasing data from the study, completed in April 2006.

Q. What's the difference between cholesterol-lowering statins and Vytorin and Zetia?

A. Statins block the formation of bad cholesterol, or LDL, in the liver, while Zetia blocks its absorption in the intestines. Vytorin is simply Zetia combined with a statin called Zocor, which is now available in generic form as simvastatin. About 60% of patients who take Zetia take it with Zocor as Vytorin.

Q: Who participated in the study?

A: The study involved 720 patients with very high levels of cholesterol from an inherited form of heart disease. The study was designed to prove that Vytorin could slow the growth of plaque in carotid arteries supplying the brain more than simvastatin alone.

Q: What were the findings?

A: The researchers found that even though Vytorin dramatically reduced bad-cholesterol levels, it did not slow the growth of artery blockages more than generic Zocor. "It's certainly not an alternative to high doses of statins, which we know work," Nissen says.

Q: Are other studies in the works?

A: Three bigger studies are underway that will test whether Vytorin can prevent heart attacks, strokes and other events in thousands of patients. The results from those studies won't be released until 2011.

Q: How can it be that a drug that dramatically lowers bad cholesterol doesn't reduce plaques?

A: The answer isn't clear. Some drugs are simply more effective than others. Statins may reap their benefits not just by lowering bad cholesterol but also by raising good cholesterol and fighting artery inflammation. Zetia and Vytorin, which work differently, only lower bad cholesterol.

Sometimes drugs do everything that's asked of them and still fail to perform. Pfizer's experimental drug torcetrapib dramatically raised good cholesterol, as doctors had hoped it would. But lab tests don't tell the whole story. Unfortunately, the drug had deadly side effects that killed its chances of approval.

Q: How do the drugs' manufacturers explain their failure in this study?

A: Lee Davies, a spokesman for the two firms' joint venture, says the patients presented a major challenge, partly because their cholesterol was so high. Also, most of them had already been treated with statins, making it harder to see any additional benefit.

Q: What's the bottom line for patients?

A. Zetia and Vytorin should not be used as first-line drugs, Blumenthal says. They're most useful for patients who aren't getting all the help they need from statins and for those who can't tolerate statins' side effects, including liver problems.

Source: usatoday.com