(NaturalNews) Documents on the FDA Web site reveal that pharmaceutical companies Merck and Schering-Plough conducted numerous safety studies on the popular cholesterol drug Zetia but did not publish the results, which suggested that the drug may cause liver damage when mixed with statins.
Zetia is a trade name for the drug ezetimibe, also marketed under the names Ezetrol and Ezemibe. It is a major seller for Merck and Schering, and is estimated to have earned them $5 billion in 2007.
The drug functions by blocking cholesterol absorption in the gut, and is often prescribed in conjunction with another class of cholesterol drugs, called statins. Because statins function in a different fashion by increasing the rate at which LDL cholesterol is cleared from the blood, the combination leads to a greater overall decrease in cholesterol levels. This combination is so popular that Merck and Schering also sell a combination Zetia-Zocor (simvastatin) pill under the brand names Vytorin and Inegy.
But concerns have long existed that the combination of Zetia and statins may lead to liver damage. As early as 2002, an FDA reviewer recommended against allowing the drugs to be mixed, due to liver damage in animal studies. Since the drug's approval, various case studies of liver damage have been published in medical journals.
The trials used to secure Zetia's FDA approval were all short-term studies, in which a total of 3,900 patients had been given Zetia for a maximum of 12 weeks. The time period covered by these studies is generally accepted to be too short for signs of liver damage to emerge in most patients. Yet even in these studies, the rate of health problems was 11 times higher among patients who took Zetia in combination with a statin than among those who took only statins. Nearly all serious health effects were liver-related.
Yet the FDA ruled that these risks were minor, and approved the drug without any request for longer term studies.
Now, careful examination of documents on the FDA web site reveals that the agency also saw the results of longer-term trials that showed more significant liver-related risks. But these studies were never published, leaving doctors and health researchers at large unaware of their results.
The exact results of the studies remain unknown. But allusions to them on the FDA Web site reveal that they were conducted between 2000 and 2003 and looked at several thousand patients who had been given a Zetia-statin combination for a period between one and two years. The statins tested include Lipitor, Crestor and Zocor, and there were signs of liver damage among patients who mixed these drugs with Zetia.
According to Robert J. Spiegel, chief medical officer at the Schering-Plough Research Institute, the results of the studies were not considered scientifically important enough for publication. But many health professionals have disputed this view.
"There is important evidence, but it's not in public view," said Dr. Harlan Krumholz, a Yale cardiologist. "It's hidden from investigators."
The concealment of the studies may also have been a violation of FDA rules that require results of all drug trials completed after October 2002 to be listed on industry Web sites.
The hidden studies' exposure comes at a time when Merck and Schering are already under fire for failing to publish the results of a large-scale trial of Zetia's effectiveness and safety, and questions are increasingly being raised as to whether the drug even provides any benefit to patients.
The companies have been criticized for their delay in releasing the data from a large-scale Zetia study called Enhance, which was completed in early 2006. The companies have acknowledged that several participants were dropped from the study early when tests revealed unusually high levels of liver enzymes in their bodies, which is a sign of liver damage. The results of the Enhance trial are not due for release until March.
In addition, while Zetia definitely lowers cholesterol levels, it has never been shown to have any effect on the heart attack risk or lifespan of patients. Dr. Eric J. Topol, a cardiologist and director of the Scripps Translational Science Institute, says that he asked the company to conduct large, long-term trials on the drug's effectiveness in reducing heart attacks and strokes more than four years ago.
"They looked at me like I was an alien," Topol said.
Merck and Schering have finally begun such a study, with a 10,000-participant pool. But the results are not expected until 2011.
Dr. Beatrice A. Golomb of the University of California at San Diego is critical of doctors who prescribe Zetia along with statins. The point of giving patients cholesterol drugs is not to lower their cholesterol levels, she points out. It is to save lives, and there is no evidence that Zetia does so. Doctors are merely taking this effect as a matter of faith, on the company's say so.
Zetia critics are not mollified by Schering's assurances that the FDA was aware of the concealed long-term studies when it approved the drug, pointing out that the agency has been slow to act on many other popular drugs when evidence of serious health risks emerged. Among these medications are the diabetes drug Avandia, the painkiller Vioxx and the anti-psychotic Zyprexa.
By concealing the results of certain studies, critics say, the companies have misled the public into believing that the drugs are safer than they are.
"You don't want to have data missing," said Dr. Bruce Psaty, a professor of medicine and epidemiology at the University of Washington. "When there have been adverse effects, when the benefits don't look impressive, those are the trials that historically don't make it to press."
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