Regular Aspirin Use Reduces Risk for Colorectal Cancer Precursors

Roxanne Nelson

February 13, 2009

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February 13, 2009 — The results of observational studies and randomized trials suggest that regular use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risk of developing colorectal adenomas, which are known precursors to colorectal cancer.

The results of 2 new studies, published in the February 18 issue of the Journal of the National Cancer Institute, add strength to the evidence that aspirin may be an effective means of chemoprevention in high-risk individuals, as previously reported by Medscape Oncology.

In the first study, which was an observational follow-up of the Aspirin/Folate Polyp Prevention Study (AFPPS), the researchers found that the risk for all adenomas was substantially reduced among patients who continued to use aspirin after 3 years. In addition, the chemopreventive effect of aspirin strengthened when used for at least 4 days per week.

Not only did prolonged and frequent use of aspirin have a strong beneficial effect, it did not lose its efficacy with continued use.

"We document that if you stop aspirin after taking it, there is no 'rebound' increase in adenoma occurrence," said senior author John A. Baron, MD, professor of medicine at Dartmouth Medical School, in Lebanon, New Hampshire. "We also found that with continued NSAID use, the chemopreventive effect does not wane."

"All this is consistent with a substantial amount of other data showing that NSAIDs, particularly aspirin, interfere with carcinogenesis in the large bowel, and have the potential to prevent colorectal cancer," Dr. Baron told Medscape Oncology. The second paper reviewed 4 randomized placebo-controlled trials and found that aspirin use might prevent a recurrence in people with a history of colorectal adenomas. The pooled analysis showed a statistically significant 17% decrease in the relative risk for adenoma for aspirin in any dose, compared with placebo, which corresponds to a 6.7% absolute risk reduction.

Effect Maintained Over Time

Using data from the AFPPS, Dr. Baron and colleagues evaluated the persistence of the protective effect after aspirin treatment was discontinued and whether efficacy was affected by the duration and frequency of NSAID use.

The AFPPS involved 1121 otherwise healthy individuals who had had adenomatous polyps removed during routine colonoscopies, and who were randomly assigned to receive placebo or aspirin (81 or 325 mg/day) for 3 years. At the end of the treatment period and after a follow-up colonoscopy, AFPPS participants were invited to remain under follow-up until their next surveillance colonoscopies, which were scheduled 3 to 5 years later.

A total of 850 participants had a posttreatment colonoscopy approximately 4 years after the study ended. The researchers observed that the protective effect of 81 mg of aspirin seen during the treatment phase of the study persisted only in participants who continued to take NSAIDs during the observational part of the trial. The risk for adenomas among frequent NSAID users (4 or more times per week) was 26.8%, compared with 39.9% among those in the placebo group who later used NSAIDs sporadically. The unadjusted absolute risk reduction was 13.1 percentage points.

They also note that the higher dose of aspirin did not confer a statistically significant reduction in adenoma risk during the randomized treatment phase and, in this analysis, people randomly assigned to high-dose aspirin and who later became frequent users had a nonstatistically significantly lower risk for all adenomas, compared with placebo users who became, at most, sporadic NSAID users (30.6% vs 39.9%). The small numbers of end points limited analysis for advanced lesions, but resultssuggested a protective effect for 81 mg of aspirin, regardless of posttreatment NSAID use.

"However, all drugs, even those as familiar and as safe as aspirin, need to be considered in the context of all possible effects — both good and bad," cautioned Dr. Baron. "NSAIDs do bring risks of [gastrointestinal] toxicity and, for aspirin, bleeding. These toxicities will have to be weighed against the benefits."

Meta-Analysis Shows Risk Reduction

In the second article, Bernard F. Cole, PhD, from the Department of Mathematics and Statistics at the University of Vermont, in Burlington, and colleagues performed a meta-analysis of available randomized clinical trials that examined the effectiveness of aspirin for reducing the risk for colorectal adenomas.

The 4 clinical trials comprised a total of 2967 participants, and all of the studies evaluated aspirin for the secondary prevention of colorectal adenomas. Aspirin doses ranged from 81 to 325 mg/day, and the median follow-up was 33 months.

Among the 2698 participants for whom colonoscopic follow-up information was available, adenomas were found in 424 (37%) of the 1156 participants randomized to placebo and in 507 (33%) of 1542 participants who received any dose of aspirin. Advanced lesions were found in 137 individuals (12%) in the placebo group and in 134 (9%) of those in the aspirin group. The greatest benefit from aspirin in any dose occurred in the first year of follow-up.

"In all studies, adverse events were uncommon, and rates of death, myocardial infarction, major bleeding, and any cancer were similar with the aspirin and placebo groups," the authors write.

Although the substantial size of the relative reduction in risk seen in this analysis indicates the potentially important health benefits of aspirin use, these benefits "need to be considered in the context of all of the health effects of aspirin, positive and negative," they conclude.

The AFPPS follow-up trial was supported in part by funding from the National Cancer Institute. The meta-analysis was supported by a research grant from Bayer AG to Dr. Baron. Dr. Baron, who is a coauthor of both articles, is currently a paid consultant to Bayer AG and a former paid consultant to Merck & Co Inc.

J Natl Cancer Inst. 2009;101:256-266, 267-276.

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