13 September 2006

More on NSAID and cox-2 dangers

Old, 'safe' painkillers found to cause same heart ills as new


From Wednesday's Globe and Mail

Some older, "safe" painkillers appear to cause the same heart problems as the much-scrutinized and discredited painkiller Vioxx, according to new research, which raises new concerns about the safety of treatments for chronic painful conditions such as arthritis.

At the same time, Vioxx itself appears to have even more side effects than previously believed, according to research published on-line yesterday by the Journal of the American Medical Association.

Three articles in JAMA feature some striking conclusions, including:

Older painkillers such as diclofenac sharply increase the risk of heart attacks in regular users.

Other traditional painkillers including meloxicam, indomethacin and perhaps even over-the-counter products such as ibuprofen may also increase the risk of heart disease.

Rofecobix (brand name Vioxx) -- already pulled from the market because it increased the risk of heart attacks and stroke -- may also cause kidney damage and heart arrhythmia (abnormal heart rhythm).

Celecoxib (brand name Celebrex) -- which is still available -- may cause heart problems, but only when taken at relatively high doses of 200 milligrams or more daily.

The painkiller naproxen does not reduce the risk of cardiovascular problems, as previous research has suggested, but it does not cause additional risk, either.

More than 30 million people worldwide take these medications, known as non-steroidal anti-inflammatory drugs, for the daily treatment of pain and inflammation. So, the potential repercussions of the findings are widespread.

NSAIDs are already known to cause gastrointestinal problems, and adding heart problems to the mix could deter patients from their use.

"It's important not to get too alarmed by these findings," said David Juurlink, a scientist at the Toronto-based Institute for Clinical Evaluative Sciences.

He said the news that taking diclofenac can increase risk by 40 per cent may alarm some users, but that they need to bear in mind that individual risk depends on dose and cardiovascular risk factors.

"All drugs have risks and benefits and data like this force us to scrutinize our behaviour," Dr. Juurlink said.

One study, led by Jingjung Zhang of Harvard Medical School in Boston, looked at the safety of cyclooxygenase 2 (cox-2) inhibitors such as Vioxx, Celebrex and valdecoxib (brand name Bextra, it has also been withdrawn from the market). The researchers combined the findings of 114 studies involving more than 115,000 patients and found that those taking Vioxx had markedly higher rates of kidney problems and arrhythmia.

Patients taking the other drugs did not have the same problems, leading Dr. Zhang to conclude that there is "no cox-2 inhibitor class effect."

The second study, led by Patricia McGettigan of the University of Newcastle in New South Wales, Australia, examined the cardiovascular risks associated with a broad range of painkillers, new and old. The review of 17 studies included more than 75,000 patients taking cox-2 inhibitors and 375,000 taking traditional NSAIDs.

Patients taking Vioxx saw their risk of heart attack double, while those taking diclofenac saw their risk increase 40 per cent. Ibuprofen increased risk by 7 per cent, a virtually negligible effect.

David Graham of the U.S. Food and Drug Administration (but who has clashed publicly with his employer about its policies), said in an editorial published by JAMA that, for patients with arthritis and other chronic conditions that require pain relief "naproxen appears to be the safest NSAID choice."

He said that while the data on Celebrex look relatively good, it is no better than traditional NSAIDs, so its use is not justified.
© Copyright 2006 Bell Globemedia Publishing Inc.