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Heart Attack Risks, Pain Relief Similar for Most Osteoarthritis Drugs

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Press Release Date: September 26, 2006

Two classes of drugs commonly used to treat osteoarthritis—non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors (a newer generation of NSAIDs)—present similar, increased risks of heart attacks while offering about the same level of pain relief, according to a new report by the Department of Health & Human Services' (HHS) Agency for Healthcare Research and Quality (AHRQ).

The exception is the drug naproxen, commonly sold as Aleve or Naprosyn, a medication that scientific evidence suggests presents a lower risk of heart attack for some patients than other NSAIDs or COX-2 inhibitors, the study concluded. Researchers emphasized in their analysis, however, that all drugs pose potential harms along with benefits. Patients differ widely on how they react to drugs, how they prioritize risks, and whether risks are acceptable when compared to a drug's benefits. Patients should talk to their doctors before changing any medications.

The report, authored by AHRQ's Evidence-based Practice Center at Oregon Health & Science University, was based on a systematic review of 360 published studies and represents the most comprehensive analysis thus far of arthritis pain medications. Researchers compared the pain medications' effectiveness and health risks, including heart attack and gastric side effects, plus identified topics where more research is needed. While the review yielded important findings about the painkillers, it concluded more studies are needed about the drugs' comparative risks, the consequences of long-term use, and the impact of dosing variations. The authors also suggested that genetic research may one day predict which patients are most likely to develop cardiovascular problems when taking the analgesics.

"These findings represent a vital comparison of medications that are taken by millions of Americans," said AHRQ Director Carolyn M. Clancy, M.D. "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."

Osteoarthritis is a joint disease that causes erosion of cartilage and leads to friction between bones. Its precise cause is unknown, though it has been linked to aging, specific occupations, trauma, genetics and repetitive, small injuries over time. The rubbing causes pain, swelling, and loss of motion. Osteoarthritis is different from rheumatoid arthritis, an autoimmune disease that causes joint pain and other problems.

Osteoarthritis affects mostly older people, but younger people with joint injuries also may be afflicted. About 6 percent of U.S. adults 30 or older have osteoarthritis of the knee, and about 3 percent have osteoarthritis of the hip. In 2003, Americans spent about $36.6 billion on treatments for osteoarthritis and other non-traumatic joint disorders, including hospitalizations, surgeries, diagnostic tests, drugs, home care and other interventions, according to federal estimates. Of this amount, about $5.5 billion was spent on COX-2 inhibitors and $3 billion on other NSAIDs.

The AHRQ report, which was developed with ongoing input from experts and other members of the public, analyzed the risks and benefits of 26 medications. Among the conclusions:

  • All NSAIDs 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 other NSAIDs or COX-2 inhibitors.
  • The risks of serious adverse gastrointestinal events for users of Celebrex are similar to the risks for users of Motrin, Advil, Voltaren 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 (Tylenol) generally reduces pain less effectively than NSAIDs but carries a smaller risk of gastrointestinal problems. One study showed high doses posed heart attack risks similar to NSAIDs.

For years, NSAIDs were the primary treatment for osteoarthritis. This class of drugs includes prescription medications, such as sulindac (sold as Clinoril) and diclofenac (Voltaren, Cataflam), as well as over-the-counter medicines such as aspirin, and medications with both prescription and over-the counter versions, such as ibuprofen (Motrin, Advil) and naproxen (Naprosyn, Aleve).

Traditional NSAIDs work by inhibiting the action of two related enzymes. One of the enzymes reduces inflammation, eases pain and prevents blood clotting. But the intervention also limits the other enzyme's ability to protect the stomach lining from digestive chemicals and help maintain kidney function. Each year, an estimated 16,500 people die due to NSAID-induced gastrointestinal problems.

Many experts initially expected that COX-2s, which target only the enzyme that stimulates inflammation, would not cause the same stomach problems as traditional NSAIDs. Unexpectedly, the drugs were linked to serious cardiovascular problems. Two COX-2 inhibitors—rofecoxib (Vioxx) and valdecoxib (Bextra)—were voluntarily withdrawn from the market because of heart attack risks. Evidence on a third COX-2 inhibitor, celecoxib (Celebrex), suggests that it does reduce the risk of bleeding and other ulcer complications in patients using the drug for less than 6 months, but it is not clear if it is safer than other NSAIDs when used for longer periods of time.

The new report, Comparative Effectiveness and Safety of Analgesics for Osteoarthritis, is the newest in a series of Comparative Effectiveness Reviews, and it is available at They are produced by AHRQ's Effective Health Care Program, the first federal program to compare alternative treatments for health conditions and make the findings public. The program is intended to help patients, health care providers, and others choose the most effective treatments. Information on the program and other comparative effectiveness reviews can be found at

For more information, please contact AHRQ Public Affairs: (301) 427-1855 or (301) 427-1998.


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