August 10, 2012
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Aspirin’s effect on cancer mortality may be more modest than previously believed

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A daily aspirin regimen reduced overall cancer mortality, but the benefit may be less significant than previously believed, according to results of a large cohort study.

Eric J. Jacobs, PhD, the strategic director of pharmacoepidemiology with the Epidemiology Research Program at the ACS in Atlanta, and colleagues evaluated data from 100,139 patients (44,360 men and 55,779 women) who participated in the Cancer Prevention Study II Nutrition Cohort.

Upon study entry, the patients had no cancer history, and all of them had been taking a daily dose of aspirin. The researchers evaluated the patients’ continued aspirin intake through follow-up questionnaires.

Patients were followed for up to 11 years. Between 1997 and 2008, 5,138 study participants (5.1%) died from cancer.

The researchers determined daily aspirin usage at baseline was associated with slightly lower cancer mortality, and the benefit did not vary based on duration of the regimen (RR=0.92; 95% CI, 0.85-1.01 for <5 years; RR=0.92; 95% CI, 0.83-1.02 for ≥5 years).

Analyses that used updated information from the follow-up questionnaires showed a stronger association, suggesting daily aspirin usage reduced cancer mortality by 16%. Once again, the benefit existed regardless of duration of daily use (RR=0.84; 95% CI, 0.76-.95 for <5 years; RR=0.84; 95% CI, 0.75-0.95 for ≥5 years).

In contrast, a recent pooled analysis of randomized trials designed to evaluate aspirin’s ability to prevent vascular events showed 5 years of daily aspirin reduced overall cancer mortality by 37% (RR=.63; 95% CI, 0.49-0.82; P=.0005).

“Our results provide additional support for a potential benefit of daily aspirin use for cancer mortality, but important questions remain about the size of this potential benefit,” Jacobs and colleagues wrote. “However, even a relatively modest benefit with respect to overall cancer mortality could still meaningfully influence the balances of risk and benefits of prophylactic aspirin use.”

In the current study, the lower overall mortality was driven by a nearly 40% reduction in mortality from gastrointestinal tract cancers — including colorectal, stomach and esophageal cancers — and a nearly 12% reduction in mortality from cancers outside the gastrointestinal tract, according to researchers.

Jacobs and colleagues acknowledged a potential limitation of their report, noting their data are from an observational study rather than a randomized trial.

“We could have underestimated the size of any reduction in cancer mortality from aspirin use because of confounding by factors associated with both daily aspirin use and increased cancer mortality,” Jacobs and colleagues wrote. “Alternatively, we could have overestimated any reduction in cancer mortality if daily aspirin use was associated with factors that reduce cancer mortality — for example, promptly seeking medical attention in response to early symptoms of cancer.”

Also, the study included a limited number of former long-term daily aspirin users. Consequently, researchers were unable to determine if long-term aspirin users experience lower cancer mortality even after they stop taking aspirin, a benefit suggested by prior studies.

In an accompanying editorial, John A. Baron, MD, a professor of medicine at the University of North Carolina School of Medicine, noted the ACS analysis showed no association between aspirin use and cancer mortality among former or current smokers. Reports from the prior cardiovascular trials suggested smoking did not alter the aspirin mortality benefit.

Overall, Baron said the study by Jacobs and colleagues serves as “an echo of other data on aspirin and cancer mortality, not a resounding confirmation.”

“The big picture on aspirin use and cancer is very positive,” Baron wrote. “However, just because aspirin is effective does not mean it necessarily should be used. Aspirin is a real drug, with definite toxicity. As for any [preventive] intervention, the benefits must be balanced against the risks, particularly when the benefits are delayed whereas the risks are not.”

For more information:

  • Jacobs EJ. J Natl Cancer Inst. 2012; Published online ahead of print Aug. 10.
  • Rothwell PM. Lancet. 2012;doi:10.1016/S0140-6736(11)61720-0.