Journal of the National Cancer Institute Advance Access originally published online on February 10, 2009
JNCI Journal of the National Cancer Institute 2009 101(4):267-276; doi:10.1093/jnci/djn484
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© The Author 2009. Published by Oxford University Press.
ARTICLES |
Nonsteroidal Anti-inflammatory Drug Use After 3 Years of Aspirin Use and Colorectal Adenoma Risk: Observational Follow-up of a Randomized Study
Affiliations of authors: Departments of Community and Family Medicine, Dartmouth Medical School, Hanover, NH (MVG, ELB, JG, JAB); Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC (RSS); Department of Public Health Sciences and Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada (GM-E); Department of Gastrointestinal Medicine and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX (RSB); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (RWH); Department of Medicine, University of Colorado Health Science Center, Denver, CO (DJA); Division of Gastroenterology/Hepatology, University of Iowa Carver College of Medicine, Iowa City, IA (RWS); Department of Medicine, Dartmouth Medical School, Hanover, NH (JAB)
Correspondence to: Maria V. Grau, MD, MPH, 420 Bayberry Dr, Chapel Hill, NC 27517 (e-mail: maria.grau{at}dartmouth.edu).
Background: Frequent use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce the risk of colorectal adenomas in randomized trials. We examined the persistence of the protective effect after the cessation of randomized aspirin treatment and whether it is affected by the duration and frequency of subsequent NSAID use.
Methods: We used data from the Aspirin/Folate Polyp Prevention Study (AFPPS), in which 1121 subjects were randomly assigned to receive placebo or aspirin (81 or 325 mg/d) for 3 years. After the end of treatment and a follow-up colonoscopy, AFPPS participants were invited to remain under follow-up until their next surveillance colonoscopies, scheduled 3–5 years later. Information regarding use of NSAIDs during posttreatment follow-up was gathered periodically via questionnaires. Average weekly NSAID use was classified as sporadic (<2 days per week), moderate (2 to <4 days per week), or frequent (
4 days per week). The analysis was stratified according to randomized aspirin groups and posttreatment NSAID use; placebo subjects who later were sporadic NSAID users formed the reference group. The primary outcomes were all adenomas and advanced lesions. Adjusted relative risks and 95% confidence intervals were computed with generalized linear models. All statistical tests were two-sided.
Results: A total of 850 subjects underwent a posttreatment colonoscopy, on average 4 years after the end of study treatment. The protective effect of 81 mg of aspirin for colorectal adenomas persisted with continued posttreatment NSAID use. The risk of any adenoma among frequent NSAID users was 26.8% vs 39.9% among placebo subjects who later used NSAIDs sporadically (adjusted relative risk = 0.62, 95% confidence interval [CI] = 0.39 to 0.98; Ptrend with NSAID use frequency = .03). The unadjusted absolute risk reduction was 13.1 percentage points (95% CI = –0.3 to 26.5 percentage points) (P = .07). Results for 325 mg of aspirin were similar, although not statistically significant. For advanced lesions, small numbers of endpoints limited the analysis, but findings among subjects randomly assigned to 81 mg of aspirin suggested a protective association regardless of posttreatment NSAID use.
Conclusion: Long-term and frequent use of NSAIDs may enhance the chemopreventive effect of aspirin against colorectal neoplasia.
| CONTEXT AND CAVEATS Prior knowledge Randomized trials have demonstrated that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of colorectal adenomas. However, it is unclear whether this protective effect persists after the cessation of randomized NSAID treatment and/or is affected by the duration and frequency of subsequent NSAID use. Study design An observational follow-up of the Aspirin/Folate Polyp Prevention Study, in which 1121 subjects who were randomly assigned to receive placebo or aspirin for 3 years were, after the end of treatment and a follow-up colonoscopy, invited to remain under follow-up until their next surveillance colonoscopies. Information regarding the subject’s use of NSAIDs and other medications during follow-up was obtained periodically via questionnaires. Contribution The risk of all adenomas was substantially reduced among subjects who continued to use NSAIDs after 3 years of aspirin treatment in the randomized trial. There was an apparent strengthening of the chemopreventive effect of aspirin associated with use of NSAID for at least 4 days per week. Implications Long-term and frequent use of NSAIDs may enhance the chemopreventive effect of aspirin against colorectal neoplasia. Limitations Due to the observational nature of the study, the findings are susceptible to bias and confounding. The study subjects are not representative of the general population. Small numbers of advanced lesions limited the statistical power of some analyses. The questionnaires did not capture dose information. From the Editors
|
Manuscript received May 6, 2008; revised October 31, 2008; accepted November 26, 2008.
Related Article in JNCI
CiteULike 
Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2009 101: 215.
This article has been cited by other articles:
|
|
 |
|
  Aspirin to Prevent Colorectal Adenomas Journal Watch (General), March 19, 2009; 2009(319): 2 - 2. [Full Text]
|
|