Nonsteroidal anti-inflammatory drugs, or NSAIDs, which include ibuprofen and COX-2 inhibitors such as celecoxib, or Celebrex, are widely used medications in the treatment of arthritis, because they help relieve pain and reduce inflammation. But a study in the British Medical Journal says these medications also increase the risk of heart attacks and strokes. Doctors say this is a finding that people with chronic conditions, such as rheumatoid arthritis and even obesity, need to pay attention to since many already face a higher risk of heart problems.

“The main finding is that we have found surprisingly large signals for most of the NSAIDs – for all except naproxen. There’s a two- to fourfold increase in myocardial infarction, stroke or cardiovascular deaths,” explains study author Peter Jüni, MD, head of the division of clinical epidemiology and biostatistics at the Institute of Social and Preventive Medicine at the University of Bern in Switzerland. “We were surprised the signals were so high.”

NSAIDs are the most commonly used drugs; researchers reported that 5 percent of all doctor visits in the U.S. involve a prescription for NSAIDs. But since 2004, there have been questions about these painkillers’ association with cardiovascular trouble after rofecoxib, or Vioxx, was pulled from the market when it was found to increase the risk of heart problems. Swiss researchers wanted to see if there was an increased risk with other common painkillers, too.

They studied data from 31 trials involving more than 116,00 patients taking one of seven medications: naproxen, ibuprofen, diclofenac, which is sold as Voltaren and Cataflam, and four COX-2 inhibitors – although celecoxib, or Celebrex, is the only one currently available in the U.S. The researchers did not include aspirin, another NSAID, in this review, because there were no large-scale studies of it at doses high enough to provide relief of pain and inflammation. (Low-dose aspirin, less than 325 milligrams, often used to lower cardiovascular risk, was not a part of this review.) 

According to the researchers, the data from the 31 studies found that 554 people in 29 trials had heart attacks, 377 people in 26 trials had strokes and 676 people in 28 trials died.

Compared with placebo, the risk of stroke was three times higher with ibuprofen, and the risk of dying from heart trouble was four times greater in those on diclofenac or the COX-2 inhibitor etoricoxib, which is sold under the brand name Arcoxia. Two COX-2 inhibitors – rofecoxib, or Vioxx, and lumiracoxib, or Prexige – doubled heart attack risk. 

(In 2007, the U.S. Food and Drug Administration declined to approve etoricoxib, and lumiracoxib.)  

Researchers say they know a lot of people with arthritis and other chronic inflammatory conditions already have a high risk of cardiovascular disease, but they also depend on NSAIDs. Dr. Jüni says, in light of their findings, these patients need to carefully consider what they’re taking and for how long they’re taking it.

“Ideally it would be best to take only [NSAIDs for] one or two weeks and then discuss with doctors other alternatives,” Dr. Jüni says. Patients can help minimize harm by staying active and doing muscle-strengthening and aerobic exercises to keep fit and reduce pain, says Dr. Jüni. He says people who are overweight should try to lose weight, which also can reduce joint pain.

“If they have a lot of pain and lost weight and still have problems, it may be surgical interventions are needed,” he adds.

The study found naproxen, or Aleve, to be the safest NSAID, but Dr. Jüni warns that it’s not without side effects; it can cause gastrointestinal problems that may require additional medication to protect the stomach.

Daniel Furst, MD, a rheumatologist at UCLA Medical Center, points out that these data are actually not new, although more quantitative.

“The increased relative risk of two to four times has been known for years,” Dr. Furst says. “My take is that patients who need to take NSAIDs should do so with appropriate cautions [to protect their health] – exercise, a good diet, weight loss if needed. [And doctors should] consider their patients’ background – previous heart attack, family history, etc.

“As always, one needs to consider the whole story and the whole patient, not just the literature data,” says Dr. Furst.