Long-term use of nonsteroidal anti-inflammatory drugs is associated with a reduced incidence of oral cancer in smokers but also with an increased risk of death due to cardiovascular disease, researchers reported in the October 15 issue of The Lancet.
Jon Sudbø, M.D., senior consultant, Department of Medical Oncology and Radiotherapy, Norwegian Radium Hospital, Oslo, Norway, and colleagues took a retrospective look at data collected prospectively from 1975 to 1995 on more than 123,000 adults participating in the Norwegian Health Survey. The survey tracks participants’ lifestyles, habits and long-term health outcomes.
The researchers narrowed their focus to 454 people with oral cancer and 454 others without such malignancies matched for age and sex. All of the subjects had a history of heavy smoking.
"Specifically, we were looking for associations between the long-term use of traditional, non-COX-2-specific NSAIDs and the risk of oral cancer, since previous work has suggested that these drugs can lower risks for other malignancies, such as colon cancer," explained researcher Scott M. Lippman, M.D., Ellen F. Knisely Distinguished Chair and chairman, Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston.
The researchers found that adults who were prescribed NSAIDs such as aspirin, ibuprofen, naproxen, indomethacin, piroxicam and ketoprofen for six months or longer (in most cases, for much longer periods) had a 53 percent lower risk of developing oral malignancies compared with those who did not take the drugs over the long-term.
"But there was a puzzling finding," Dr. Sudbø said. "Even though the drugs appeared to protect users from oral cancer, we saw no added benefit overall in terms of prolongation of life or reduced mortality. So something was potentially tipping the balance the other way."
The researchers identified that "something" as cardiovascular disease. According to the study, long-term use of traditional NSAIDs, except for cardiovascular-dose aspirin, doubled users’ risk of dying of cardiovascular disease.
The investigators stressed that the study has limitations. First, the NSAIDs used in the study were available to Norwegians via prescription only, and it is not clear whether dosages used by the survey participants were similar in strength to those of popular American over-the-counter products.
In addition, the researchers emphasized that although the data themselves were collected prospectively, the study remains a relatively small, retrospective effort. The results need to be confirmed by much larger, prospective trials, they said.
The study was funded by grants from the National Cancer Institute, the Center for Cancer Prevention Research, the Norwegian Cancer Society, the Research Foundation of the Norwegian Radium Hospital, Astrid and Birger Torsteds Legat and the Research Council of Norway.
