If you regularly take medication for some arthritis pain, you may be wondering if the treatment is worse than the disease. Concerns that some popular drugs widely prescribed for arthritis and inflammation may put patients at greater risk for serious cardiovascular events have recently had their 15 minutes of infamy. Here's why.

What's the Problem?

The drugs most in question are a type of non-steroidal anti-inflammatory drug (NSAID) that stops production of one type of cyclooxygenase (COX), an enzyme involved in making prostaglandins. Among other things, prostaglandins play a role in the painful, inflammatory response to injury. Some prostaglandins also are thought to "turn on" pain receptors.

General NSAIDs, like the familiar Advil or Motrin (ibuprofen), block production of both types of cyclooxygenase, COX-1 and COX-2.

COX-1 is involved in activities such as platelet activation, gastrointestinal processes and kidney function. COX-2 is produced mainly as a response to tissue damage and injury.

Drugs such as Vioxx, Celebrex and Bextra that have caused the most recent concern are called COX-2 inhibitors because they block production of COX-2 without affecting COX-1. This was a good thing at first-these drugs appeared to stop pain and inflammation without upsetting your stomach, causing bleeding or damaging kidneys.

COX-2 inhibitors are now associated with higher risks of blood clots, strokes and heart attacks than their older cousins, the general NSAIDS (ibuprofen, naproxen and aspirin). These cardiovascular accidents may be related to the drug's failure to block platelet activation, a heart-protective effect of COX-1 drugs. The COX-2 drugs, however, are thought to offer greater protection against gastrointestinal side effects of long-term NSAID therapy, such as stomach bleeding and ulcers.

Premature Panic?

"We clearly need more data," says John D. Reveille, MD, professor and director of the Division of Rheumatology at The University of Texas Medical School at Houston. "It is premature for every patient to stop using these medications; but patients with established heart disease, high cholesterol or diabetes or those with kidney disease should be a lot more cautious." COX-2 drugs are much more expensive than other NSAIDS, Reveille points out, "and there is no indication that they are any more effective. And now we know about the possible vascular problems."

No Lingering Drug Effects

Prior Vioxx or other COX-2 patients should not have lingering negative effects after stopping therapy, Reveille says. If you had no symptoms while you were taking the drug, it is unlikely that future symptoms will appear. However, the COX-2 inhibitors should be taken only if you cannot tolerate possible gastrointestinal side effects of other NSAIDs. Most patients should be able to use other types of NSAIDs.

'Over the Counter' Does Not Equal 'Safe'

Reveille also warns that even over-the-counter NSAIDs should be taken only as directed on product labeling, for short-term use.

"Anybody taking NSAIDs long term, especially at doses exceeding what the over-the-counter NSAIDs have recommended, should be followed by his or her physician and have blood tests once or twice a year to check for kidney or liver problems," he warns. "The frequency of side effects is also dose-related, so those taking higher doses (such as ibuprofen 800 mg four times a day or naproxen 500 mg twice a day) should be monitored."

Reveille says that if you are taking the drugs only to relieve periodic pain, such as muscle ache or headache, acetaminophen (Tylenol) could suffice.

However, any medication, even over-the-counter products, can be associated with problems if taken over a long period and at a high dosage. Recently the National Institutes of Health halted a study after three years when researchers found that patients taking a general NSAID, a well-known over-the-counter medication (naproxen), had a 50 percent greater incidence of cardiovascular events, heart attack or stroke after three years of use than patients in the study not taking the drug.

Acetaminophen also can be dangerous to the liver if dosage recommendations aren't followed.

Alternative Treatment

There are over 100 types of arthritis. In some, such as gout or rheumatoid arthritis, NSAID use is probably necessary. But in the most common type, osteoarthritis, which affects up to 40 percent of the population, alternatives to NSAIDs exist:

• Acetaminophen (Tylenol) a pain reliever only, with no anti-inflammatory properties
• Tramadol, an analgesic which also works by raising one's pain threshold
• Certain topical creams containing capsaicin (active ingredient of chile peppers) that appears to reduce pain and stiffness. Other topical creams/gels generally mask the pain with a heat or cold sensation, serving more as a distracter.
• Physical therapy
• Ice and moist heat: ice to temporarily reduce local swelling; moist heat to temporarily relieve stiffness
• Dietary changes
• Exercise
• Acupuncture
• Therapeutic massage

As is often the case, the risks versus the potential benefits of any drug should be considered before planning long-term treatment with them. Meanwhile, further studies that test the true safety of NSAIDs, especially selective COX-2 inhibitors, should be carried out.

Last Updated: 2-01-2005

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