RESEARCH - NSAIDS halve oral cancer risk, but double cardiovascular risk

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NSAIDs halve oral cancer risk, but double cardiovascular risk

Rheumawire

Oct 7, 2005

Gandey

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.

" 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 rheumawire. " 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 rheumawire, preliminary findings of this study

were presented in February at a US Food and Drug Administration hearing

evaluating the safety of NSAIDs. Dr 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.

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 rheumawire, 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.

Dr Pisetsky (Duke University, Durham, NC and editor in chief of

www.jointandbone.org) said that he agreed that additional study is in order.

" I'd also like to see the issue of dosing addressed. "

Source

1. Sudbø J, Lee JJ, Lippman SM, et al. Nonsteroidal

anti-inflammatory drugs and the risk of oral cancer: A nested case-control

study. Lancet 2005; DOI:10.1016/S0140-6736(05)67488-0. Available at:

http://www.thelancet.com.

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