A randomized trial of aspirin to prevent colorectal adenomas

N Engl J Med. 2003 Mar 6;348(10):891-9. doi: 10.1056/NEJMoa021735.

Abstract

Background: Laboratory and epidemiologic data suggest that aspirin has an antineoplastic effect in the large bowel.

Methods: We performed a randomized, double-blind trial of aspirin as a chemopreventive agent against colorectal adenomas. We randomly assigned 1121 patients with a recent history of histologically documented adenomas to receive placebo (372 patients), 81 mg of aspirin (377 patients), or 325 mg of aspirin (372 patients) daily. According to the protocol, follow-up colonoscopy was to be performed approximately three years after the qualifying endoscopy. We compared the groups with respect to the risk of one or more neoplasms (adenomas or colorectal cancer) at least one year after randomization using generalized linear models to compute risk ratios and 95 percent confidence intervals.

Results: Reported adherence to study medications and avoidance of nonsteroidal antiinflammatory drugs were excellent. Follow-up colonoscopy was performed at least one year after randomization in 1084 patients (97 percent). The incidence of one or more adenomas was 47 percent in the placebo group, 38 percent in the group given 81 mg of aspirin per day, and 45 percent in the group given 325 mg of aspirin per day (global P=0.04). Unadjusted relative risks of any adenoma (as compared with the placebo group) were 0.81 in the 81-mg group (95 percent confidence interval, 0.69 to 0.96) and 0.96 in the 325-mg group (95 percent confidence interval, 0.81 to 1.13). For advanced neoplasms (adenomas measuring at least 1 cm in diameter or with tubulovillous or villous features, severe dysplasia, or invasive cancer), the respective relative risks were 0.59 (95 percent confidence interval, 0.38 to 0.92) and 0.83 (95 percent confidence interval, 0.55 to 1.23).

Conclusions: Low-dose aspirin has a moderate chemopreventive effect on adenomas in the large bowel.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoma / mortality
  • Adenoma / prevention & control*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Aspirin / adverse effects
  • Aspirin / therapeutic use*
  • Colonic Polyps / diagnosis
  • Colonic Polyps / prevention & control
  • Colonoscopy
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / prevention & control*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Patient Compliance
  • Risk
  • Secondary Prevention

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Aspirin