Gastroenterology

Gastroenterology

Volume 134, Issue 1, January 2008, Pages 29-38
Gastroenterology

Clinical–Alimentary Tract
Aspirin and Folic Acid for the Prevention of Recurrent Colorectal Adenomas

https://doi.org/10.1053/j.gastro.2007.10.014Get rights and content

Background & Aims: Although observational studies have found regular aspirin use to be associated with a reduced risk of colorectal neoplasia, results from randomized trials using aspirin have been inconsistent. Dietary folate intake also has been found to be associated with a reduced risk of colorectal neoplasms in observational studies. Methods: A multicenter, randomized, double-blind trial of aspirin (300 mg/day) and folate supplements (0.5 mg/day) to prevent colorectal adenoma recurrence was performed using a 2 × 2 factorial design. All patients had an adenoma (≥0.5 cm) removed in the 6 months before recruitment and were followed-up at 4-month intervals with a second colonoscopy after approximately 3 years. The primary outcome measure was a colorectal adenoma diagnosed after baseline. Results: A total of 945 patients were recruited into the study, of whom 853 (90.3%) underwent a second colonoscopy. In total, 99 (22.8%) of 434 patients receiving aspirin had a recurrent adenoma compared with 121 (28.9%) of 419 patients receiving placebo (relative risk, 0.79; 95% confidence interval [CI], 0.63–0.99). A total of 104 patients developed an advanced colorectal adenoma; 41 (9.4%) of these were in the aspirin group and 63 (15.0%) were in the placebo group (relative risk, 0.63; 95% CI, 0.43–0.91). Folate supplementation was found to have no effect on adenoma recurrence (relative risk, 1.07; 95% CI, 0.85–1.34). Conclusions: Aspirin (300 mg/day) but not folate (0.5 mg/day) use was found to reduce the risk of colorectal adenoma recurrence, with evidence that aspirin could have a significant role in preventing the development of advanced lesions.

Section snippets

Study Design

The ukCAP study was a double-blind, randomized, placebo-controlled trial performed in 10 study centers (9 in the UK and 1 in Denmark, see list in Appendix). A 2 × 2 factorial design was used to allow separate assessments of both aspirin and folic acid in preventing the recurrence of colorectal adenomas. Recruitment for this study occurred between December 1997 and November 2001; the last patient completed the study in July 2005. Ethical approval for the study was gained independently for each

Results

A summary of recruitment is provided in Figure 1. A total of 945 patients were recruited into the trial (307 recruited from East Midlands, 82 from Birmingham, 103 from Bristol, 77 from Liverpool, 43 from Manchester, 33 from Blackpool, 79 from Belfast, 59 from South Yorkshire, 112 from South Wales, and 50 from Denmark). Six patients were classified as having been recruited in error. This included 1 patient for whom consent was withdrawn after 2 months of medication. In the remaining cases,

Discussion

In this randomized, double-blind trial the ukCAP investigators set out to determine whether aspirin (300 mg/day) or folate (0.5 mg/day) were effective in reducing the recurrence of colorectal adenomas in patients who had previous adenomas removed at colonoscopy. We found this dose of aspirin to have an effect, reducing the recurrence rate of adenomas of any size by 21%, and of advanced adenomas by 37%. Folate supplementation had no significant effect on adenoma recurrence.

In interpreting the

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    Supported by a grant from Cancer Research UK (formerly the Cancer Research Campaign).

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