Study: Vioxx danger to heart, kidneys

Philadelphia, Pennsylvania, New Jersey and New York

Potentially fatal side effects occurred as soon as a month after starting treatment, a new report said.

By Michelle Fay Cortez and Angela Zimm
Bloomberg News
Wednesday, September 13, 2006

Merck & Co. Inc.'s withdrawn Vioxx pain reliever raised heart and kidney risks, in some cases within a month of starting treatment, according to data included in reviews of 137 studies that looked at a family of similar drugs.

The reviews conclude that Vioxx's potentially fatal side effects are not seen in all other pills included in the drugs known as cox-2 inhibitors, taken for pain from arthritis, muscle injuries and headaches. The researchers did not find a similar danger from Pfizer Inc.'s Celebrex, while diclofenac, an older drug used outside the United States, had risks similar to Vioxx.

The results, published yesterday by the Journal of the American Medical Association, may pose a setback for Whitehouse Station, N.J.-based Merck, which faces more than 16,000 lawsuits and argues that Vioxx is not a threat unless taken for 18 months. Merck has major operations in the Philadelphia area.

For tens of thousands who had heart attacks while on Vioxx, "the drug may have been the decisive risk factor, over and above any other risk factors, that contributed to the occurrence of this life-changing and potentially fatal event," wrote David J. Graham, a Food and Drug Administration official, in an accompanying editorial.

The reviews were done by researchers at Harvard Medical School in Boston and by scientists at the University of Newcastle in New South Wales. One review found more vigorous monitoring would have uncovered kidney risk linked with Vioxx by 2000 and heart-rate roblems by 2004. The other review linked heart attacks to Vioxx within 30 days after treatment begins.

"Merck believes that observations published in today's Journal of the American Medical Association, and the opinions expressed in an accompanying editorial regarding a potential increased short-term cardiovascular thrombotic risk of Vioxx, are not supported by the current weight of the clinical trial data," the company said yesterday in an e-mailed statement.

Cox-2 drugs were developed in the 1990s as a safer alternative to other painkillers that can cause stomach bleeding, such as naproxen, an older generic medicine.

Graham, who raised questions about Vioxx's safety before it was withdrawn in September 2004, spared neither the agency he works for nor pharmaceutical companies from criticism in an editorial that accompanied the studies. The comments reflect his own views, not those of the agency, he wrote.

"Merck practiced a campaign of misinformation by presenting data that violated rules of science, they weren't called to account by the journals that published their articles, and you have an FDA that hasn't been held to account," Graham said yesterday in a telephone interview. "There is a lot of blame to go around."

In the editorial, Graham criticized Merck for the way it conducted studies of Vioxx and its successor, Arcoxia. Merck is seeking U.S. clearance of Arcoxia, which is approved in 62 countries in Europe, Asia and South America.

When a study dubbed VIGOR showed cardiovascular risks were five times higher for people on Vioxx than those on naproxen, Merck and researchers suggested the older pain drug protected the heart. A collection of smaller studies involving Arcoxia suggested its heart risk is similar to the older drug diclofenac, implying it is safe.

One study showed diclofenac users were most likely to have heart attacks or other heart problems among people taking the nonsteroidal anti-inflammatory drugs. And while naproxen did not seem to harm the heart, it did not protect the organ either.