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Heart Attack Risks, Pain Relief Similar For Most Osteoarthritis Drugs

Two classes of drugs commonly used to treat osteoarthritis, a painful disease that causes joints to slowly erode, have similar, increased risks of heart attacks and offer about the same level of pain relief, according to a new report released by the Department of Health and Human Services' Agency for Healthcare Research and Quality (AHRQ).

The exception is the drug naproxen, commonly sold as Aleve or Naprosyn. Scientific evidence suggests naproxen presents lower heart attack risk than other NSAIDs - non-steroidal anti-inflammatory drugs - and COX-2 inhibitors, a newer generation of NSAIDs.

In their analysis, however, the researchers state 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 with a drug's benefits. Patients should talk to their health care provider before changing any medications.

The report was written by AHRQ's Oregon Evidence-Based Practice Center, a consortium of clinicians and researchers from Oregon Health & Science University, Kaiser Permanente Center for Health Research, and the Portland Veterans Affairs Medical Center. To create this report, the researchers conducted a systematic review of 360 published studies. The report represents the most comprehensive analysis thus far of arthritis pain medications.

"Our report underscores the importance of considering all of the potential risks and benefits before starting an NSAID or a COX-2 inhibitor. In particular, the increase in heart attack risk seen with all NSAIDs other than naproxen has only recently emerged from the evidence and should be considered before starting treatment," said lead author and Oregon EPC investigator Roger Chou, M.D., M.P.H. Chou also is an assistant professor of medicine, medical informatics and clinical epidemiology, OHSU School of Medicine.

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 Carolyn M. Clancy, M.D., AHRQ director. "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.
*    It is unclear if the risks of serious adverse gastrointestinal events for users of Celebrex are smaller than the risks for users of Motrin, Advil, Voltaren and other NSAIDs when the drugs are taken for more than six months.
*    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 six 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. 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

Oregon Health & Science University is Oregon's only health and research university and its only academic health center. As Portland's largest employer and the fourth largest employer in Oregon (excluding government), OHSU's size contributes to its ability to provide many services and community support activities not found anywhere else in the state. It serves more than 184,000 patients, and is a conduit for learning for more than 3,900 students and trainees. OHSU is the source of more than 200 community outreach programs that bring health and education services to each county in the state.

As a leader in research, OHSU earns $294 million annually in research funding. The institution serves as a catalyst for the region's bioscience industry and is an incubator of discovery, averaging one new breakthrough or innovation every four days. OHSU disclosed 101 inventions in 2005 alone and has helped start 57 new spinoff companies, most of which are based in Oregon.


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