One of the most comprehensive analyses of the risks and benefits of oral nonsteroidal anti-inflammatory drugs (NSAIDs) – a class of painkillers commonly used by patients with rheumatoid arthritis and osteoarthritis  – spells out the risk of heart attack, stroke, heart failure and upper gastrointestinal (GI) complications of each different kind of drug.

The review, published recently in The Lancet online, shows that diclofenac (Voltaren, Pennsaid, Cataflam) increases the risk of heart attack or stroke by about a third when taken at high doses. The study found that diclofenac’s risk is similar to that of selective COX-2 inhibitors, such as celecoxib (Celebrex), which have been known to elevate a person’s risk. (The COX-2 drug Vioxx was pulled from the market in 2004 because of an increased risk of heart attack and stroke.) That means that compared to placebo, for every 1,000 patients taking either celecoxib or diclofenac, there were three additional heart attacks or strokes, one of which was fatal.

High doses of ibuprofen (Advil, Motrin) also showed a similar increase in risk of heart attack. Naproxen (Aleve, Naprosyn) was not found to significantly increase the risk of either heart attack or stroke.

All NSAIDs – ibuprofen, naproxen, diclofenac and COX-2 inhibitors – doubled the risk of heart failure (when the heart can’t pump enough blood to meet the body’s needs). They also increased the risk of upper GI problems (mostly bleeding) by two to four times. The GI risks appeared to be somewhat lower for the COX-2 inhibitors and diclofenac compared to ibuprofen or naproxen.

“This represents the most comprehensive analysis ever conducted on the benefits and risks of these classes of drugs,” explains study coauthor Charles H. Hennekens, MD, a senior academic advisor to the dean at the Charles E. Schmidt College of Medicine at Florida Atlantic University in Boca Raton. "These results should help guide health care providers in their prescribing patterns."

The analysis was based on a review of more than 600 randomized trials involving more than 353,000 patients; the vast majority of the health risks were in trials involving “high doses” of NSAIDs. High doses were characterized as 2,400 milligrams (mg) a day of ibuprofen, 150 mg a day of diclofenac and 1,000 mg a day of naproxen.

Dr. Hennekens says these findings suggest these medications are likely safe in the short-term for acute pain, but says caution is needed if they’re taken long-term. “These data do demonstrate long-term risks of cardiovascular and gastrointestinal disease which should be weighed against the clear benefits for treating the pain of arthritis,” Dr. Hennekens explains.

Marie R. Griffin, MD, a professor of preventive medicine at Vanderbilt University School of Medicine in Nashville, Tenn., agrees. Dr. Griffin, who was not involved in the study, says the data show the longer you take these drugs the greater the risk. “Taking them for short periods of time, especially at lower doses, they are pretty safe drugs. But when you have people with chronic pain who take these pills every day, day after day, month after month, you start to get into a risky situation and I think people probably don’t understand that fully,” she explains.

Dr. Griffin says patients with arthritis should consider whether NSAIDs are really helping them – especially because they only relieve pain without improving the underlying condition. “I sometimes see patients who say, ‘The pills don’t really work much but maybe it would be worse without them,’ or ‘I’m not sure I can tell a difference,’” Dr. Griffin explains. “In that situation – where the drugs aren’t making a big difference  – then they really need to think about whether they are getting enough benefit to [justify] the risk they are taking on.”

She says patients with arthritis should consider other ways to control their pain including physical therapy, weight loss, joint-friendly exercises (like walking or swimming) and perhaps a pain management program. “These things may be harder to do than taking a pill, but they don’t have as many long-term side effects,” Dr. Griffin says.

She says patients should try to figure out how much the drugs are helping by perhaps lowering the dose to see if it is still effective, or even going on a drug holiday. She says patients should ask themselves: “Do I need this much and would I be just as well off using less or only using it intermittently or is it making any difference in my life at all?”

Dr. Hennekens notes that these aren’t decisions people should make on their own. “For many patients suffering from the severe and disabling pain of inflammatory arthritis, the benefits may outweigh the risks,” he says. “But this judgment should be made by the health care provider in consultation with each patient.”