A new study adds to growing concerns about the heart safety of painkillers taken by millions of Americans. It shows that smokers who regularly take certain nonsteroidal anti-inflammatory drugs (NSAIDs) double their risk of dying of heart disease.

The study, presented at the annual meeting of the American Association for Cancer Research, was designed to test whether the anti-inflammatory drugs could prevent oral cancer among heavy smokers.

It showed NSAIDs do indeed have that protective effect, reducing the risk of oral cancers in smokers by about half. The analysis included aspirin, ibuprofen (sold as Motrin, Advil, and others), naproxen (Aleve and others), indomethacin, piroxicam, and ketoprofen. Acetaminophen (Tylenol) was also included but is not an NSAID.

Nevertheless, for most people seeking to reduce their risk of oral cancer, the risks of taking NSAIDs appear to outweigh the benefits, says chief investigator John Sudbo, MD, PhD, DDS, a cancer researcher at the Norwegian Radium Hospital in Oslo.

Raymond DuBois MD, PhD, director of the Vanderbilt-Ingram Cancer Center and moderator of a news conference about the findings, agrees.

"You don't want to do something that will make people worse," he says.

A better strategy against oral cancer would be to quit smoking, Sudbo tells WebMD. "Smoking cessation is as effective at preventing oral cancer as using NSAIDs. Both cut the risk by about 50 percent," he says.

Some Painkillers Pulled From Market

DuBois says the National Cancer Institute will host a meeting in May to address emerging information about NSAID toxicity.

At first, heart risks seemed to be confined to a small group of NSAIDs called Cox-2 inhibitors -- Bextra, Vioxx, and Celebrex. Vioxx was pulled from the market last fall when a study testing whether it could prevent recurrent colon polyps showed a higher heart disease risk. Recently, manufacturer Pfizer stopped selling Bextra for heart safety reasons, but Pfizer's Celebrex is still on the market.

The study's findings suggest that other types of NSAIDs also pose a risk to the heart.

Painkillers Lower Risk of Oral Cancer

The new study followed more than 3,000 smokers enrolled in the Norwegian Cancer Registry, a database of more than 123,000 people.

Over a 20-year period, 454 of them developed oral cancer; they were compared with 454 smokers who did not develop cancer. Of these 908 people, 277 were long-term NSAID users, meaning they used the medications for at least six months.

The study showed that years of NSAID use were associated with lowered oral cancer risk.

Those who took NSAIDs for five years or less had about half the risk for oral cancer compared with nonusers. Those who used them for 15 to 26 years were 70% less likely to develop oral cancer.

At the Heart of the Matter

But the researchers were puzzled because the NSAID users did not live longer. The data were so surprising that "we thought the data were corrupt," Sudbo says.

A closer look revealed the reason why: NSAID users were twice as likely to die from heart-related problems. There were 42 cardiovascular-disease deaths among 263 high-risk, long-term NSAID users and 41 cardiovascular deaths among 562 people who had never taken such drugs.

People who took ibuprofen were at highest risk: They were nearly three times more likely to die of heart disease than non-NSAID users.

Aspirin did not seem to increase the risk of dying from heart disease, but "with only 14 patients taking aspirin the numbers are too small to know if it was a [statistical fluke]," Sudbo says.

The NSAID dose did not seem to make a difference in risk, but this needs future study, he says.

By Charlene Laino, reviewed by Brunilda Nazario, MD

SOURCES: 96th Annual Meeting of the American Association for Cancer Research, Anaheim, Calif., April 16-20, 2005. John Sudbo, MD, PhD, DDS, cancer researcher, Norwegian Radium Hospital, Oslo. Raymond DuBois MD, PhD, director, Vanderbilt-Ingram Cancer Center.