Study Blames Vioxx for Up to 140,000 Cases of Heart Disease

As many as 40 percent of cases may have been fatal, FDA scientist contends

MONDAY, Jan. 24, 2005 (HealthDayNews) -- As many as 140,000 excess cases of serious coronary heart disease may have been caused by the now-withdrawn arthritis drug Vioxx since it hit the U.S. market in 1999, a new report contends.

And up to 40 percent of those cases may have been fatal, the study author claims.

The study, released late Monday by the British medical journal The Lancet, was led by Dr. David Graham, associate director for science at the U.S. Food and Drug Administration's Office of Drug Safety. He has been a longstanding critic of Vioxx, a cox-2 inhibitor drug that was pulled from the market in September by Merck & Co., after studies showed it could lead to increased risk of heart attack and stroke.

Dr. Eric Topol, chairman of cardiovascular medicine at the Cleveland Clinic and a critic of cox-2 drugs who has authored several editorials on the subject, said, "This [Graham's conclusion] seemed very reasonable. It's still conservative. With so many tens of millions of people exposed, it doesn't take that much risk to get these sorts of numbers."

The new study is the latest round in a drama that could have implications for millions of Americans who took Vioxx or are taking others in the cox-2 class or in the wider category of nonsteroidal anti-inflammatory drugs (NSAIDs).

For the new study, Graham and his colleagues looked specifically at side effects associated with Vioxx and with two other NSAIDs, Celebrex and naproxen, in a population of 1.4 million people who were enrolled in a managed-care plan in California and had used NSAIDs from the beginning of 1999 through September 2004.

Overall, they found, those taking Vioxx had a 59 percent higher risk of coronary heart disease than those taking Celebrex. Those taking a lower dose of Vioxx had a 47 percent increased risk while those taking a higher dose had a 360 percent increased risk.

People taking naproxen, best known as Aleve, had a 14 percent increased risk of coronary heart disease. This is contrary to previous studies, which had suggested that naproxen protected against coronary heart disease.

The study did not find an increased risk with Celebrex use.

According to the research, 106.7 million prescriptions for Vioxx were written from 1999 to September 2004 for patients in the United States. And the researchers reported that troubles with Vioxx tended to start early on, meaning heart problems became apparent soon after people started taking the drug.

Graham contended that between 88,000 and 140,000 excess cases of serious heart disease could have been caused by the drug.

The new Lancet paper was originally supposed to have been published on Nov. 17, a day before Graham testified before Congress on what he said were the FDA's shortcomings when it came to monitoring drugs for safety. But the paper was withdrawn on Nov. 16.

At the time, Graham said, the FDA threatened him with "serious consequences" if he proceeded with publication of the study. "The FDA did everything in its power to suppress [the findings] and keep them from public view," Graham contended.

FDA officials later relented and granted Graham permission to resubmit the paper.

"It's an important analysis," Topol said. "It has a big base of patients. It is a very strong new piece of supportive information that this can occur very early, that the risk does not appear to be time-dependent and it's confirmed now in the largest population ever."

In an interview, Graham said that he had published the article "so that the medical community and the general public would be able to see the real-life consequences of the FDA's having failed to protect the public."

"People can now begin to focus seriously on what I believe is a major public health and policy question that faces Congress and faces the American people, which is, do we want additional Vioxx-like catastrophes and are we going to do anything to ensure that what happened with Vioxx doesn't happen again," he continued.

"The FDA is on record as saying that all of its decisions about Vioxx were appropriate and that basically, faced with the same information again, FDA would make the same decision again and there would be another 100,000 or 140,000 people with heart attacks and sudden death," Graham said.

The FDA, which is now reviewing the safety profile of all cox-2 inhibitors, did not respond Monday to a request for comment.

As for his own future, Graham said, "I'm still at FDA doing drug safety research. I hope I'm able to continue. The last three months have been extremely difficult, and the FDA has spent quite a bit of effort battering and maligning and threatening me and trying to intimidate me."

"The fact that the article is finally published to me, at least, is vindication of our science," he added. "FDA officials called it 'junk science' and I think that The Lancet has said in a resounding manner that it's anything but."

Meanwhile, also on Monday, a new report in another medical journal charged that Merck & Co. forced a researcher to remove her name from a study linking Vioxx to heart attacks a year before the drug was pulled from the market.

Two of the scientist's colleagues, writing in the Jan. 24 issue of Archives of Internal Medicine, said the company publically discredited their findings, according to an Associated Press report. A Merck spokeswoman confirmed the company's action, saying Merck believed the study's conclusions "were not supported by the data," AP reported.

More information

The Arthritis Foundation has more on NSAIDs.

SOURCES: David J. Graham, M.D., associate director, science, Office of Drug Safety, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Rockville, Md.; Eric J. Topol, M.D., chairman, department of cardiovascular medicine and chief academic officer, Cleveland Clinic; Jan. 24, 2005, The Lancet
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