Aspirin Helps Prevent Recurrent Large Bowel Adenomas

SAN FRANCISCO—Routine use of aspirin provides a modest reduction in the recurrence of large bowel adenomas, according to the results of a randomized, double-blind, placebo-controlled study presented by the Polyp Prevention Study Group. Paradoxically, the group found that an 80 mg daily dose, the equivalent of one baby aspirin, was much more effective in preventing polyps than was the 325 mg daily dose, the amount contained in a typical adult aspirin.

John A. Baron, MD, professor of medicine, Dartmouth Medical School, presented the findings at the 93rd Annual Meeting of the American Association for Cancer Research (abstract 3319).

"It is clear that aspirin will not be, at least alone, a magic bullet. No one can take a daily aspirin and then expect to forget about everything else—not see a physician, not be screened," Dr. Baron said. "Aspirin use will have to be integrated into the routine care of patients under the advice of a physician."

The study was performed by researchers at nine centers in the United States and Canada. Study subjects had at least one histologically documented adenoma removed within 3 months of study entry and had no remaining polyps on colonoscopy. Patients who already were routinely taking aspirin were excluded, as were individuals with known polyposis or hereditary cancer. The majority were male (63.5%) and white (85.5%), and 15% were smokers.

Study Design

All of the patients took 325 mg aspirin daily for 3 months to identity individuals for aspirin sensitivity and noncompliance. The 1,121 remaining subjects were then randomly assigned to placebo (n = 372), 80 mg aspirin (n = 377), or 325 mg aspirin (n = 372).

"These two doses were tested because they reflect amounts often used for heart disease prevention, and we wanted to be consistent in our study to avoid the possibility of conflicting recommendations for these two health issues at a future date," Dr. Baron said.

Lower Dose More Effective

After a median follow-up of 34 months, the adenoma recurrence rate was 47% for the placebo group, 38% for the lower-dose aspirin group, and 45% for the higher-dose aspirin group (P = .04). Compared with placebo, risk reductions were 19% for 80 mg aspirin and 4% for 325 mg aspirin.

Both doses were more effective in reducing the incidence of more aggressive adenomas. Compared with placebo, the risk reductions for cancers or adenomas with tubulovillous or villous histology were 40% for the lower-dose aspirin group and 19% for the higher-dose group.

Dr. Baron did not know why the 80-mg dose was more effective than the 325-mg dose. "Frankly, I can’t explain it," he said.

Compliance was excellent during the study. More than 90% of patients said that they took at least half of their pills, and less than 8% took additional NSAIDs for more than a few days during any 4-month period during the study, which was the limit recommended by the study’s researchers.

Almost all of the subjects (97%) had a follow-up colonoscopy between 1 and 3 years after randomization. Only five patients developed a carcinoma, and nine died during the study period.

"The safety profile was excellent," Dr. Baron said. "There were some GI bleeds, but not more than expected." However, he did express concern about the potential for eventual serious side effects, considering the number of years that patients would have to take aspirin to reduce their risk of developing polyps. He was hesitant to recommend the widespread use of daily aspirin based on the results of this one study.

"If patients already have vascular disease, atherosclerotic disease, then clinically I believe aspirin is probably indicated anyway. Polyp prevention is just another benefit for these individuals," Dr. Baron said.

He is not as enthusiastic about recommending aspirin for adenoma prevention for patients who do not otherwise need to take the drug on a daily basis. "I don’t feel that we have a secure understanding of the magnitude of the aspirin effect in polyp prevention. So, consequently, I’m personally reluctant to tell these people, ‘yes, take aspirin now,’" Dr. Baron concluded.

The study also examined the influence of folate supplementation on polyp development. That part of the investigating is ongoing and was not included in the presentation.