Journal of the National Cancer Institute Advance Access published online on February 10, 2009
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djn485
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© The Author 2009. Published by Oxford University Press.
ARTICLES |
Aspirin for the Chemoprevention of Colorectal Adenomas: Meta-analysis of the Randomized Trials
Affiliations of authors: Department of Mathematics and Statistics, University of Vermont, Burlington, VT (BFC); Department of Epidemiology and Public Health, Queens Medical Centre, University of Nottingham, Nottingham, UK (RFL, MJG); Department of Biostatistics and Bioinformatics and the Cancer and Leukemia Group B Statistical Center, Duke University Medical Center, Durahm, NC (SH); Department of Gastroenterology, Hopital Avicenne, Bobigny, France (RB); Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC (RSS); Department of Gastroenterology, Hopital Cochin–Université René Descartes, Paris, France (SC); Department of Community and Family Medicine (BFC, JAB) and Department of Medicine (JAB), Dartmouth Medical School, Hanover, NH
Correspondence to: Bernard F. Cole, PhD, Department of Mathematics and Statistics, University of Vermont, 16 Colchester Ave, Burlington, VT 05401 (e-mail: ccole{at}cems.uvm.edu).
Background: Multiple lines of evidence indicate that aspirin has an antineoplastic effect in the large bowel. Randomized clinical trials have been conducted to evaluate the effectiveness of aspirin for reducing the risk of colorectal adenomas. A meta-analysis of these trials will provide more precise estimates of the aspirin effect, both overall and in subgroups.
Methods: We combined data from all randomized double-blind placebo-controlled trials that evaluated aspirin for the prevention of colorectal adenomas. We used random-effects meta-analysis to estimate risk ratios and 95% confidence intervals (CIs) for the effect of aspirin on the occurrence of adenomas and of advanced lesions (ie, tubulovillous adenomas, villous adenomas, adenomas 
1 cm in diameter, adenomas with high-grade dysplasia, or invasive cancer). All statistical tests were two-sided.
Results: We identified four clinical trials with 2967 randomly assigned participants. Each trial evaluated aspirin for the secondary prevention of colorectal adenomas. Doses of aspirin tested ranged from 81 to 325 mg/d. The average age of participants at baseline was 58 years, and 60% were male. Median follow-up was 33 months. A total of 2698 participants underwent colonoscopic follow-up and were included in the analysis of adenoma occurrence and advanced-lesion occurrence after randomization. Among these participants, adenomas were found in 424 (37%) of the 1156 participants allocated to placebo and in 507 (33%) of the 1542 participants allocated to any dose of aspirin. Advanced lesions were found in 12% of participants in the placebo group and in 9% of participants allocated to any dose of aspirin. The pooled risk ratio of any adenoma for any dose of aspirin vs placebo was 0.83 (95% CI = 0.72 to 0.96). This corresponded to an absolute risk reduction of 6.7% (95% CI = 3.2% to 10.2%). For any advanced lesion, the pooled risk ratio was 0.72 (95% CI = 0.57 to 0.90). We found no statistically significant effect modification for any of the baseline factors studied.
Conclusion: Aspirin is effective for the prevention of colorectal adenomas in individuals with a history of these lesions.
| CONTEXT AND CAVEATS Prior knowledge Multiple lines of evidence including clinical trial data indicate that aspirin has an antineoplastic effect in the large bowel and reduces the risk of colorectal adenomas. However, a quantitative summary of efficacy is missing. Study design A meta-analysis of the association between aspirin use and the occurrence of adenomas and of advanced lesions using participant data from four randomized double-blind trials that evaluated higher-dose and/or lower-dose aspirin vs placebo for the secondary prevention of colorectal adenomas. Contribution Among 2698 participants who underwent colonoscopic follow-up after randomization, adenomas were found in 37% of those allocated to placebo and in 33% of those allocated to any dose of aspirin (advanced lesions were found in 12% and 9%, respectively). Implications This meta-analysis of clinical trial data indicates that aspirin reduces the risk of recurrence of colorectal adenomas. Limitations Dose–response patterns were not interpretable because only two studies investigated lower-dose aspirin. An analysis of cardiovascular and bleeding events was limited by the small numbers of events observed in any one trial. One trial was excluded from the analysis of adverse events. From the Editors
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Manuscript received May 9, 2008; revised November 17, 2008; accepted December 1, 2008.
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J Natl Cancer Inst 2009 101: 215.
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