Merck issues worldwide recall of Vioxx

NEW YORK, Sept. 30 (UPI) -- Drug giant Merck said Thursday it is voluntarily withdrawing Vioxx, its popular arthritis and pain drug, from the market in response to studies linking long-term use to increased risk of heart attack and stroke.

In a hastily called New York news conference, Raymond Gilmartin, Merck's chairman and chief executive officer, said the company decided to withdraw the drug after reviewing results from a three-year study that found people taking Vioxx daily for more than 18 months were twice as likely to have a heart attack or stroke as people taking placebos. The cardiovascular event rate was 15 per 1,000 patients in the Vioxx arm vs. 7.5 per 1,000 patients in the placebo group.

Peter Kim, president of Merck Research Laboratories, said there was no increase in mortality in the Vioxx group.

"There were five cardiovascular deaths in each arm," Kim said.

The 2,600-patient study was designed to test the ability of Vioxx, which is a member of a class of drugs called Cox 2 inhibitors, to prevent the recurrence of colon polyps.

A secondary aim of the study was the assessment of cardiovascular risk, Kim said. Since Vioxx was approved in 1999, other studies have suggested the drug was associated with increased risk of heart attack and stroke, but in the past the company vigorously challenged those claims. Merck argued the drug had been unfairly linked to heart disease because earlier studies compared Vioxx to an older arthritis drug, naproxen. Naproxen, said Kim and Martin, is known to protect the heart, which skews any effort at comparison.

Kim said the company learned about the cardiovascular risks late last week and spent the past several days deciding what action to take and informing regulatory authorities. Martin said the company decided to withdraw the drug, even though it felt assured the drug could be safely marketed with labeling changes.

The voluntary withdrawal of the drug, used by more than 2 million people worldwide, will have a immediate and negative impact on Merck shares, Martin said. Originally, the company projected earnings from $3.11 to $3.17 per share, but Martin said the "per-share earnings as a result of this announcement will be negatively affected by 50 to 60 cents per share."

He said the company is retracting its third quarter guidance statement. By mid-afternoon Thursday, Merck shares trading on the New York Stock Exchange had lost about 27 percent of their value.

One of the first physicians to raise questions about Vioxx was Cleveland Clinic cardiologist, Dr. Steven Nissen, the lead author of the August 2001 Journal of the American Medical Association article that reported an increased risk of heart attack and stroke for Vioxx and Celecoxib, a cox-2 inhibitor made by Pfizer, although the risk was greater for Vioxx users.

Nissen told United Press International he had "no self-satisfaction in seeing the drug withdrawn because that is always a tragedy," but he applauded Merck's decision to withdraw the drug.

"We took a scientific gamble in publishing (the JAMA) article because we didn't have a lot of information, but it is to JAMA's credit that the journal decided that the information belonged in the public domain," Nissen said.

He added that in the years since the article was published, "there has not been a lot of data emerging that Celebrex is similarly risky, so that drug does look clean so far." The Merck decision, however, is likely to "heighten surveillance of all Cox 2 drugs." In addition to Celebrex, a third Cox 2 inhibitor, Bextra, also made by Pfizer, is currently available in the United States.

Nissen said he thinks the increased risk associated with Vioxx is likely to diminish shortly after the drug is stopped.

"We think the mechanism involved here is a pro-thrombotic effect, so when the drug is stopped and out of the system that risk is likely to disappear," he said.

Drugs that have pro-thrombotic effects make the blood stickier and more likely to form clots that block blood flow in the heart or brain, which causes heart attacks and strokes.

Dr. Alice Jacobs, president of the American Heart Association, told UPI that patients taking Vioxx should contact their physicians to discuss the implications of the Merck announcement.

"A patient's individual physician is the best person to evaluate individual risk," said Jacobs, who also is a professor of cardiology at Boston University.

She cautioned that when drugs are withdrawn -- blockbuster drugs such as Vioxx in particular -- it may set off panic among patients.

"There is no need for us to scare patients about this, especially when there are other drugs available to treat arthritis," she said.

Kim emphasized that the study findings do not affect another Cox 2 inhibitors, adding Merck is continuing to pursue Food and Drug Administration approval for Arcoxia, a new Cox 2 inhibitor that is already approved in more than 40 countries.

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Peggy Peck covers research and health issues for UPI Science News. E-mail sciencemail@upi.com