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Public release date: 21-Jul-2008


In the latest disappointment for cholesterol pill Vytorin, a major European study in patients with heart valve disease found the drug didn’t prevent worsening of the disease or lower the need for valve surgery, sending its makers’ stock plunging.

Results of a preliminary analysis of the just-completed study showed Vytorin, marketed jointly by Merck & Co. and Schering-Plough Corp., was no better than placebo at lowering the risk of major cardiovascular events — including heart attack, stroke, heart surgery and death — in patients with aortic stenosis.

The sometimes deadly condition, which is becoming increasingly common in elderly people, involves partial blockage and stiffening of the aortic valve, which sends oxygen-rich blood through the aorta and throughout the body. More than 5 million Americans have the disease to some extent, and it’s the No. 2 cause of heart surgery.

Researchers at 173 hospitals and other sites in Europe were hoping the study, called SEAS, would show that Vytorin offers a nonsurgical way to treat aortic stenosis by reducing bad cholesterol and plaque buildup.

That wasn’t the case, although Vytorin did cut cholesterol levels about 60 percent.

But Vytorin, which combines Merck’s Zocor — now available as a cheap generic — with Schering-Plough’s Zetia, didn’t do anything to protect patients’ heart valves and raised fears, apparently unfounded, that it increased risk of cancer.

“You don’t help that (valve) disease, but you do help the patients” by protecting other heart blood vessels and reducing heart attacks and the need for bypass surgery or artery-clearing angioplasty, Sir Richard Peto, an Oxford University statistician and cancer expert who analyzed the data, told The Associated Press in an interview.

The 1,873-patient study, just ended in March, did find that secondary benefit, but it’s already well-documented that some cholesterol-lowering drugs reduce the risk of heart attack and stroke.

The cholesterol-lowering and reduced heart complications are consistent with what’s been shown with Zocor alone, said Cleveland Clinic cardiologist Dr. Steven Nissen, who recommends that Vytorin and Zetia not be used as first-line drugs.

“We are left with just as many questions about the efficacy of Vytorin (as before), and we have new questions about the safety,” he said, referring to the excess cancer cases and deaths in Vytorin users.

When data analysis began, the researchers were startled to see about 50 percent more new cancer cases and cancer deaths in patients who received Vytorin, compared with those who took a placebo. Peto, who is co-director of Oxford’s clinical trial service unit, then rushed to crunch data from the new study with patient data from two much-larger, ongoing Vytorin studies.

Peto and other researchers, speaking on a hastily organized, trans-Atlantic teleconference with reporters, said combining data from all three trials showed there was no elevated risk of cancer. In addition, they noted that if Vytorin were somehow triggering cancer, new cases would first become more common after several years and would be concentrated on one type of cancer, rather than many. Neither was the case.

“This absolutely excludes the idea of a 50-percent increase in risk,” Peto said of the multi-study analysis.

Dr. Harlan Krumholz, a Yale University cardiologist, said he doubts Vytorin causes cancer.

“If I’m a patient considering taking it, it still bothers me,” he said, adding that until the other Vytorin studies are finished in a few years, it will remain unclear whether and how the drug benefits patients beyond what Zocor and other statins do.

The drug’s makers deemed the results important enough to take the highly unusual step of releasing their quarterly earnings reports Monday after the stock market closed, rather than first thing in the morning as scheduled. Wall Street worries about what the study might show sent shares of both companies down sharply.

Earlier this year, a long-delayed study called ENHANCE found pricey Vytorin was no better at reducing plaque buildup than generic Zocor, which has been on sale for two years.

Two congressional committees have been probing whether the companies deliberately delayed releasing that data to prop up sales of Vytorin, which the companies denied. But after more details from the ENHANCED study were released in March, prominent cardiologists urged doctors to go back to older, well-proven treatments for high cholesterol.

Many apparently did. Last week, Schering-Plough reported the number of U.S. prescriptions filled for Vytorin and Zetia had both fallen by just over 25 percent from January to June, when total cholesterol drug sales were down about 5 percent. Vytorin prescriptions alone dropped from 1.84 million in January to 1.33 million in June.

Shares of Kenilworth, N.J.-based Schering-Plough finished Monday down $2.49, or 11.6 percent, to $18.95, while shares of Whitehouse Station, N.J.-based Merck were down $2.35, or 6.2 percent, to $35.33.

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