Oslo, Norway - While nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with preventing several types of cancer, this promise may be negated by the effect these drugs have on increasing the risk of cardiovascular-disease-related death, new data suggest [1]. The paper, published online before print October 6, 2005 in the Lancet, reveals that despite a roughly 50% risk reduction for oral cancer after NSAID use, the observed benefit was offset by an alarming increase in cardiovascular risk, resulting in no effect on mortality.

Dr Jon Sudbø (Source: Norwegian Radium Hospital)

"It is clear from these data and others that we can no longer use these drugs as indiscriminately as we have in the past," lead author Dr Jon Sudbø (Norwegian Radium Hospital, Oslo) told heartwire. "We need to be looking for patients at risk of cardiovascular events, we need to be monitoring patients more closely, and we should also be reconsidering whether NSAIDs should be used for extended periods of time."

As previously reported by heartwire, preliminary findings of this study were presented in February at a US Food and Drug Administration hearing evaluating the safety of NSAIDs. Dr David Graham, from the agency's Center for Drug Evaluation and Research, presented the work and showed that traditional NSAIDs increase cardiovascular risk, with hazard ratios ranging from 1.70 for naproxen to 2.86 for ibuprofen.

It is clear from these data and others that we can no longer use NSAIDs as indiscriminately as we have in the past.

In this nested case-control study, the researchers evaluated information from a population-based database that consisted of prospectively obtained health data from all regions of Norway. Known as the cohort of Norway, or CONOR, the database identified more than 9200 people at risk of oral cancer because of a history of heavy smoking. People who smoked 15 or more pack years who had oral cancer were matched with controls selected from the remaining heavy smokers. In all, Sudbø and his team studied 454 people with oral cancer and 454 matched controls. A total of 263 of the participants had used NSAIDs, 83 had taken acetaminophen (paracetamol), and 562 had used neither drug.

"Our finding that long-term use of NSAIDs was associated with a reduced risk of oral cancer—including in active smokers—is novel," the researchers write. "The magnitude of the protective effect of NSAIDs against oral cancer was comparable to that of smoking cessation." They point out that these results are consistent with growing evidence that extended use of NSAIDs reduces the risk of cancers of the lower gastrointestinal tract.

But the investigators found that the cancer-protective effect of NSAID use did not translate into increased overall survival, since long-term NSAID use doubled the relative risk of death due to cardiovascular disease. They found that 16% of NSAID users died of cardiovascular events compared with 7% of nonusers.

During an interview with heartwire, Sudbø emphasized that prolonged NSAID use for cancer prevention should be entertained only in high-risk cases. "This is the only setting where the risk might be justified," he said. Sudbø and colleagues are currently working on a randomized trial of celecoxib (Celebrex, Pfizer) for the prevention of oral cancer. And they emphasize that prospective randomized controlled studies investigating the relationship between NSAID use and cardiovascular disease are needed.