Assessment of Aspirin Use. Discussion
In this large prospective cohort study, regular aspirin use (defined as _2 tablets/wk) was associated with a statistically significant 25% reduction in the risk for sporadic colorectal adenomas in an average-risk population. Of note, the greatest reduction in risk was observed at doses greater than 14 standard tablets per week. Moreover, a similar dose–response relation was observed among regular short-term (_5 years) and long-term (_5 years) aspirin users. In contrast, increasing duration of aspirin use was not significantly associated with risk after adjusting for aspirin dose. Controlling for other known or suspected risk factors for colorectal adenoma and cancer did not alter these findings. Although our study was limited to women, previous reports have also demonstrated an association between reduced risk for colorectal adenoma and aspirin use in men. Results from 2 intervention trials of patients with a history of adenoma or a history of colorectal cancer have established a chemopreventative influence of aspirin on recurrent adenomas after 3 years. However, these studies examined limited doses and yielded conflicting data. The trial of patients with previously documented colon cancer demonstrated a statistically significant reduction in incidence of colorectal adenomas in patients randomly assigned to standard-dose aspirin. In contrast, the trial of postpolypectomy patients did not observe any reduction in adenoma incidence in a group randomly assigned to standard-dose aspirin but did observe a moderate benefit in a group randomly assigned to lowdose aspirin. The results of several earlier studies are consistent with our findings that higher doses of aspirin may be needed for the optimal prevention of colorectal adenomas.
The Physicians’ Health Study, a randomized, placebocontrolled trial, found a relative risk of 0.86 for adenoma among men randomly assigned to low-dose aspirin (325 mg of aspirin every other day). With only 263 total cases, this did not achieve statistical significance but was consistent with our results in the low-dose categories. In a recent French trial that assessed adenoma recurrence, the rate of adenoma recurrence at 1 year was 25% among patients randomly assigned to receive 300 mg of daily soluble aspirin compared with 35% among patients randomly assigned to receive 160 mg per day. However, this difference also did not achieve statistical significance because both aspirin groups had included only 126 patients. A posthoc analysis of a dietary intervention trial found a substantially lower incidence of recurrent adenomas among participants who reported use of more than 1 standard aspirin tablet per day compared with those who used lower doses. In a nested cohort study conducted in the United Kingdom, 300 mg of aspirin per day was associated with a statistically significant reduction in adenoma risk, whereas no benefit was seen with daily doses of either 75 or 150 mg. Finally, a randomized trial of the cyclooxygenase- 2 inhibitor celecoxib demonstrated that high, but not standard, doses significantly reduced adenoma burden in patients with familial polyposis.