The arthritis dilemma: When drugs help but also hurt patients

A federal agency sorts through the many options for this common condition but finds, not surprisingly, that all have downsides.

By Susan J. Landers — Posted Nov. 6, 2006

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Relieving arthritis pain is a big deal for patients and physicians, but doing so safely continues to pose problems.

Nonsteroidal anti-inflammatory drugs, including aspirin, present gastrointestinal risks, and the briefly shining stars in the new "coxib" subset of nonsteroidals were soon tarnished when they were found to elevate cardiovascular risk.

The Agency for Healthcare Research and Quality spotted the quandary doctors face and conducted an evidence-based analysis of the risks and benefits of 26 arthritis pain medications available via prescription or over the counter. Although the findings, published Sept. 26, failed to find a magic bullet, they do represent the most comprehensive review to date of the complex world of arthritis pain medication.

Just days after the AHRQ report's release, the Centers for Disease Control and Prevention published new figures that emphasize how large the nation's arthritis problem already is and how it likely will get worse.

In its Oct. 13 Morbidity and Mortality Weekly Report, the CDC revealed that more than 21% of adults, or 46.4 million people, said they had physician-diagnosed arthritis. Of these, more than 8%, or 17.4 million U.S. residents, said arthritis pain causes them to limit some of their activities. As the population ages, arthritis is expected to affect an estimated 67 million adults in the United States by 2030, according to the CDC.

Although the AHRQ report revealed no simple solutions, it did lay out the issues. "These findings represent a vital comparison of medications that are taken by millions of Americans," said AHRQ Director Carolyn M. Clancy, MD, in a statement. "The report also shines a bright light on questions that could further our knowledge and give patients research-based evidence to help them choose the best available treatment."

A useful report?

The report provoked a range of comments from physicians and others who treat arthritis pain.

April Vallerand, PhD, RN, associate professor at Wayne State University College of Nursing in Detroit, found it a useful tool. "In a very nice, succinct manner, it puts the issues on the line and helps physicians sort through the benefits and risks for each individual patient, which is truly how we have to manage pain today."

But Terry Moore, MD, director of rheumatology at Saint Louis University, did not find the report very useful. "It's just one study," Dr. Moore said.

Among its findings is that the two classes of drugs commonly used to treat osteoarthritis, the older nonsteroidals and the newer COX-2 selective NSAIDs, carry similar risk of heart attacks while providing about the same level of pain relief.

"I think previous studies had shown less cardiovascular effects with NSAIDs and some of the COX-2 inhibitors, whereas this study shows a pretty much equivalent effect, except for naproxen, on cardiovascular events," Dr. Moore said.

The report found that naproxen, marketed as Aleve or Naprosyn, seemed to pose a lower risk of heart attacks for some patients than did other NSAIDs or the COX-2 inhibitor subset.

"I just wish there were better options," said Dr. Vallerand, who helped draft the American Pain Society's guidelines for treating arthritis pain, which cover nutrition, exercise, and the use of over-the-counter and prescription drugs and opioids. "You look through the report, and it says there are problems with everything."

NSAIDs had been a mainstay of arthritis treatment for years. They include prescription medications such as sulindac, sold as Clinoril, and diclofenac, sold as Voltaren or Cataflam, as well as over-the-counter remedies such as ibuprofen and naproxen. But each year, an estimated 16,500 people die due to NSAID-induced gastrointestinal problems, the AHRQ noted.

With the introduction of the COX-2 inhibitors, the GI problems were thought to be history. But serious cardiovascular events soon led to the voluntary withdrawal in 2004 of two of the drugs, Vioxx, or rofecoxib, and Bextra, or valdecoxib.

Celebrex, or celecoxib, is the last of the group on the market.

As a management technique for patients taking nonsteroidals, Dr. Moore recommends frequent testing -- every four months -- to check on toxicity. Blood counts, urinalyses and metabolic panels would reveal problems in patients before they became serious, he said.

A history of cardiovascular disease also would be an indication that the NSAIDs aren't the best choice for those patients, he noted.

After reviewing the report, Robert Lahita, MD, PhD, professor of medicine at Mount Sinai Medical School in New York City and chair of medicine at the Jersey City Medical Center in New Jersey, thought its message could be boiled down to a sentence: "If you have high blood pressure, if you have edema, if you have angina or congestive heart failure or gastrointestinal problems like GERD or impaired kidney function, you should not be on these drugs. That's it."

And most primary care physicians know all that, he said.

The report presents some "pretty scary stuff," he said. "If patients see this, they won't be taking anything."

Dr. Vallerand hopes that a take-away message doesn't become "learn to live with the pain."

"I think that is absurd, since there are so many options," she said. "I think the key to this will be to individualize to a particular patient."

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Risks and benefits

The Agency for Healthcare Research and Quality's Evidence-based Practice Center at Oregon Health & Science University analyzed studies on 26 arthritis pain relievers and reached the following conclusions:

  • All nonsteroidal anti-inflammatory drugs and COX-2 inhibitors can cause or worsen hypertension, congestive heart failure, swelling and impaired kidney function.
  • No clear difference has been shown in pain-relief effectiveness among NSAIDs and COX-2 inhibitors.
  • Most NSAIDs and COX-2 inhibitors pose similar increased risks of heart attack.
  • The NSAID naproxen carries a smaller risk of heart attack than do other NSAIDS or COX-2 inhibitors.
  • The risk of serious adverse gastrointestinal events are similar for users of celecoxib as for users of ibuprofen, diclofenac and other NSAIDs.
  • More scientific evidence is needed to compare the cardiac and gastrointestinal risks of aspirin at doses effective for pain relief versus other NSAIDs.
  • Acetaminophen generally reduces pain less effectively than NSAIDs but carries a smaller risk of gastrointestinal problems. One study showed that high doses pose heart attack risks similar to NSAIDs.

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External links

Agency for Healthcare Research and Quality's report on osteoarthritis drugs (link)

"Prevalence of Doctor-Diagnosed Arthritis and Arthritis-Attributable Activity Limitation -- United States, 2003-2005," Morbidity and Mortality Weekly Report, Oct. 13 (link)

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