It is this non-selective inhibition of both enzymes by aspirin and other non-selective NSAIDs that increases the risk of stomach ulcers and consequent bleeding. In theory, the newer COX-2 selective inhibitors only inhibit the enzyme involved in inflammation, leaving the other functions alone.
But Sandra Kweder, M.D., deputy director of the Food and Drug Administration's Office of New Drugs, says that new studies have had a surprising twist. "The downside of the COX-2 selective inhibitors is that they appear to be associated--particularly when used for many consecutive months to years--with an increased risk of cardiovascular problems," she says. Moreover, COX-2 inhibitors, like other NSAIDs, don't influence the course of the disease--which doctors say is a common misconception among patients--because these drugs only provide for symptom relief.
Coincidentally, preliminary results from a three-year trial on the non-selective NSAID Aleve (naproxen) also suggested that long-term use may be associated with an increased risk for cardiovascular problems.
Since the results of studies on both non-selective and selective NSAIDs are preliminary and conflict with data from earlier studies of the same drugs, the FDA issued a public health advisory in December 2004 concerning use of all NSAIDs, pending further review of data that continue to be collected. The agency has recommended, among other things, that physicians limit the use of COX-2 inhibitors until further review.
"Monitoring the drug safety of marketed products requires close collaboration between our clinical reviewers and drug safety staff to evaluate and respond to adverse events identified in ongoing clinical trials or reported to us by physicians and their patients," says Kweder. "The most recent actions concerning [NSAIDs] illustrate the vital importance of the ongoing assessment of the safety of a product once it is in widespread use."
Others Weigh In
The concerns with the safety of so many pain relievers used to treat arthritis underscores the importance of arthritis as a major health care issue in the United States. Arthritis experts, patient advocacy groups, and other health organizations also are weighing in on the uncertainty of NSAIDs, and are recognizing the need for developing new and safer medications.
