Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials.
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 >or=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.


CONCLUSIONS
Aspirin is effective for the prevention of colorectal adenomas in individuals with a history of these lesions.
Cole
Bernard F
BF
Department of Mathematics and Statistics, University of Vermont, Burlington, VT 05401, USA. ccole@cems.uvm.edu
Logan
Richard F
RF
Halabi
Susan
S
Benamouzig
Robert
R
Sandler
Robert S
RS
Grainge
Matthew J
MJ
Chaussade
Stanislas
S
Baron
John A
JA
D000236:Adenoma / Q000517:prevention & control*; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D001241:Aspirin