CHICAGO -(Dow Jones), 3/30/08- A panel of four cardiologists said said doctors should sharply cut their use of popular cholesterol-lowering drugs Vytorin and Zetia after a clinical study showed the drugs didn’t work better than less expensive statin drugs.
The study looked at whether Vytorin, which is a combination of Merck & Co.’s (MRK) Zocor and Schering-Plough Corp.’s (SGP) Zetia, was better at reducing thickening of a neck artery than Zocor, a statin drug, alone. Zocor is widely available as a generic drug known as simvastatin. Merck and Schering-Plough market Vytorin as part of a joint venture.
Vytorin and Zetia had more than a combined $5 billion in annual sales last year, although prescription levels have dropped since the beginning of the year after the initial results from the study were released, and could fall further if doctors follow the advice of their colleagues. The companies are scheduled to address the panel’s recommendations at a press conference later Sunday.
The full study results, known as Enhance, were publicly released and discussed Sunday at the American College of Cardiology’s annual meeting in Chicago and were also published online in the New England Journal of Medicine.
The study showed neither drug affected the size of patients’ artery walls even though they cut LDL, or so-called “bad” cholesterol, levels after two years on treatment. It was expected that Vytorin would have shown a small reduction in the thickness of artery walls because it lowered LDL cholesterol levels almost 30% more than levels were cut among patients on Zocor alone.
“You’ve just seen a negative trial that should change practice,” said Dr. Harlan Krumholz. “It seems to be a very strong study.”
Krumholz spoke on behalf of a panel of four doctors that included Rick Nishimura of the Mayo Clinic, Patrick O’Gara of Brigham and Women’s Hospital and Joseph Messer, with a private cardiology practice in Chicago. Financial disclosures show Krumholz has testified against Merck in Vioxx-related litigation while the other three doctors reported no financial interests or relationships with pharmaceutical firms.
“Our strongest recommendation is that people need to go back to statins,” Krumhotz said. “We really think there’s just a small group of patients who cannot get to target (cholesterol) on statins.”
He said doctors should maximize the doses of statins and then try adding other drugs such as niacin-based drugs or fibrates in an attempt to lower LDL cholesterol levels as current practice guidelines recommend.
Zetia hit the U.S. market in 2002 and Vytorin was approved in 2004. Vytorin works to target LDL cholesterol in two ways through the combination of Zocor and Zetia. Zocor, like other statins, blocks LDL production in the liver, while Zetia prevents its absorption from food in the gut.
Messer said many doctors, including himself, believed it was more effective and possibly has fewer side effects for patients to add Zetia to a lower statin dose to in order lower LDL cholesterol rather than increasing the statin alone.
Krumholz said doctors quickly “embraced” Zetia and Vytorin since they were introduced noting that 1 in 5 prescriptions written in 2006 for cholesterol- lowering drugs was either for Zetia or Vytorin.
The study, which involved 720 patients with a family history of unusually high cholesterol, showed various measurements of the carotid, or neck artery, and the femoral artery, which runs from the lower abdomen and goes through the thigh, were essentially the same at baseline, or when the study started and after patients had been treated for two years. There was also little change in the difference of new plaque formation in the arteries between the two patient groups.
The study’s lead researcher, Dr. John J.P. Kastelein, of the Academic Medical Center in Amsterdam, said he believes one reason neither drug had a large impact on patients’ arteries was because 80% of patients entering the study had already been on high doses of statin drugs.
“If you are near normal, it’s very hard to show an effect of the drug,” he said in an interview.
The study has become a lightening rod for controversy because of a delays in getting results out and proposals by the companies - which were later dropped - to change the main study goal. The last patient scans were completed in 2006 and it took more than a year for the some 40,000 images to be interpreted.
Some congressional lawmakers accused the companies of delaying the results because the firms knew the results would be negative and wanted to protect the brisk sales growth for Vytorin and Zetia. Both drugs cost more than Zocor, which is now available as a generic drug. The companies have denied the accusations.
Kastelein said he would personally keep using Zetia in patients whose cholesterol isn’t adequately lowered by high doses of statins such as Zocor. He said doctors need to wait for the results of a much larger study looking at the impact of adding Zetia to a statin drug and whether it cuts the number of heart attacks and strokes.
Late Friday, researchers of that study, known as Improve It, led by Brigham and Women’s Hospital in Boston and Duke University in Durham, N.C., announced they were increasing the number of patients in the study from about 11,000 to 18,000, a move that could fuel additional controversy. The trial expansion means the first data from the trial likely won’t be released until at least 2012, a year later than the original results were expected.
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