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13 Sep, (foodconsumer.org) - Painkilling drugs like Cox-2 inhibitors and non-steroidal anti-inflammatory drugs (NSAIDs) pose significant heart and kidney risks, two new meta-analyses have found.

Cox-2 inhibitors like Vioxx and Bextra are no longer on the market, but one study found that the heart risks conferred by Vioxx were the same whether it was taken in high or low doses.

The studies also documented the risks posed by older pain-relieving drugs like diclofenac, which happens to be the most popular and the most-widely prescribed anti-inflammatories in the world. One of the two studies found that diclofenac even when taken at normal doses increased the risk of cardiovascular events by 40 percent.

The meta-analysis is published online today by the Journal of the American Medical Association, due to public health implications. The reports will appear in the print edition on October 4.

Vioxx was touted as a blockbuster drug for its maker, Merck. Vioxx is chemically rofecoxib and belongs to a class of drugs called COX-2 inhibitors. It is a selective non-steroidal anti-inflammatory drug (NSAID) approved by the FDA in May 1999.

It was primarily used relief of the signs and symptoms of osteoarthritis, for the management of acute pain in adults, and for the treatment of menstrual symptoms. Later on the FDA approved its use in rheumatoid arthritis in adults and children.

However problems with it began emerging soon after. Merck pulled the drug following a study, which showed Vioxx doubled the risk of heart attacks and strokes in patients who took it for more than 18 months. Subsequent reports say that this risk began much earlier.

Dr David J. Graham, M.D., M.P.H., of the FDA, writes in an accompanying editorial in JAMA that the risks of Vioxx started very early "probably with the first dose." Dr. Graham was a whistle-blower during Senate hearings on the Cox-2 drugs.

A note in JAMA says that the editorial was written by Dr Graham as an officially approved outside activity in his private capacity and not as a Food and Drug Administration employee.

Patricia McGettigan, M.D. and David Henry M.B., Ch.B., of the Mater Hospital in Waratah, New South Wales, the authors of one of the studies, examined data from 23 observational studies of Cox-2 inhibitors and NSAIDs. They found that even at normal doses, older painkillers like diclofenac increase the risk of an adverse heart event by 40 percent.

The drug "appears to be harmful at commonly used doses," raising serious questions about its safety. The authors said that the regulatory status of diclofenac must be reviewed. Diclofenac is marketed as a generic drug and also under the trade names Voltaren, Cataflam, Solaraze and Arthrotec.

Dr Graham said in his editorial that there are many alternatives to diclofenac, "European consumers would be better off switching [from diclofenac] to naproxen," he wrote.

In the second analysis, Eric Ding, a graduate student in the department of epidemiology and nutrition at the Harvard School of Public Health and colleagues examined the effect of cox-2 inhibitors on kidney function. The researchers reviewed the results of 114 randomized trials involving more than 116,000 people.

While the risk of kidney damage was accentuated by Vioxx, they did not find similar risks for Bextra and Celebrex, which is the only cox-2 inhibitor left on the market. Vioxx increased risks for adverse kidney events and irregular heart rhythms, the study said.

"It is clear that Vioxx increases the risk of heart attack. And that increase in risk begins with the first tablet a patient takes," said Dr Graham. But Ding says that not all cox-2 inhibitors have the same adverse effects. "The risks of these drugs should have been made known to the public much earlier," he said, adding that "tracking drug safety may be improved by adopting an active and continuous cumulative surveillance system."

Merck is facing at least 14,000 product liability lawsuits over Vioxx. However Dr Graham said in his editorial that it was likely to press for approval of Arcoxia, which is a successor of Vioxx and a competitor for Celebrex.

Arcoxia is another COX-2 inhibitor. Merck has been a promoting it as having lower risk of bleeding stomach ulcers and other serious digestive tract complications than other NSAIDs.

Dr Graham says that as far as Arcoxia is concerned, "the FDA, academia, and the medical research enterprise are once again faced with the opportunity to forsake common sense by willfully accepting misdirection and disinformation presented in the guise of science."

He adds that the drug would pose similar heart and kidney risks as Vioxx. "We've got a drug that we know raises the risk of a heart attack -- diclofenac. And the company has used that drug as its reference to compare to Arcoxia."

"If the lessons of recent history have been learned, the FDA's concerns will now be squarely focused on patient safety rather than corporate profitability, and, ultimately, common sense will prevail," the report concluded.

To read the complete article "COX-2 Inhibitors, Other NSAIDs, and Cardiovascular Risk"
"The Seduction of Common Sense"
David J. Graham, MD, MPH
JAMA. 2006;296:(doi:10.1001/jama.296.13.jed60058), click here.

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