Authors' objectives:

The purpose of this report was to systematically review the literature on the effectiveness of aspirin (ASA), non-aspirin nonsteroidal anit-inflammatory drugs (non-ASA NSAIDs), and cyclooxygenase-2 inhibitors (COX-2 inhibitors) for the chemoprevention of colorectal cancer (CRC) and CRC-related mortality in average-risk individuals. The review also assessed the harms associated with the use of these agents and their cost effectiveness.

Authors' results and conclusions: Effectiveness for Chemoprevention: Regular use of ASA appears to be effective at reducing the incidence of CRA. Two of the four RCTs demonstrated statistically significant relative risk reductions (RRR) in CRAs (relative risk [RR]=0.44, and 0.58), whereas the remaining two RCTs, including the Physicians Health Study (PHS), showed no benefit. The pooled estimate, however, was statistically significant (RR=0.82; 95% CI: 0.7-0.95). Pooled estimates for the case-control (RR=0.87; 95% CI: 0.77-0.98) and cohort studies (RR=0.72; 95% CI: 0.61-0.85) also showed a statistically significant relative risk reduction in CRAs with ASA. The use of non-ASA NSAIDs appeared to be associated with somewhat higher RRRs (pooled estimate - RR= 0.43; 95% CI: 0.26-0.70), and based on a very limited number of studies, the RRRs are likely higher still for higher-risk individuals than for those at average risk. The regular use of ASA was associated with RRRs of 15% to 40% for CRC incidence. The pooled RR for cohort studies was 0.78 (95% CI: 0.63-0.97). The RCT data of the effect of ASA on CRC incidence was, however, negative, both in the PHS and the newly published Women's Health Study (WHS). The pooled estimates for non-ASA NSAIDs suggest somewhat greater RRRs, on the order of 30% to 40%, and longer duration of use of ASA/NSAIDs and higher doses also appear to offer greater protection. Only two observational studies considered the effect of ASA/NSAIDs on CRC mortality Among the observational studies, one study reported that CRC mortality was reduced by about 40% with ASA use for more than 15 years, whereas, the other found nonsignificant trends towards increased standardized mortality ratios for bowel and rectal cancers with ibuprofen. The recently published WHS found no benefit of ASA on CRC mortality. Harms: The use of ASA is associated with an increased incidence of important ulcer complications with RRs of 1.5 to 3.0. The annualized incidence of these events for non-ASA NSAIDs, as a group, is approximately 1.5% to 2.0% in average-risk individuals with arthritis. As a "class" COX-2 inhibitors are associated with fewer endoscopic ulcers and clinically important ulcer complications, when compared with non-ASA NSAIDs overall, with pooled RRRs of about 50% for important ulcer complications. In individuals with low-to-average cardiovascular (CV) risk (i.e., the primary prevention population), ASA significantly reduced the incidence of total CV events, but had no effect on coronary heart disease mortality, fatal and nonfatal stroke events, or all cause mortality. In highrisk CV patients (i.e., secondary prevention), the use of ASA significantly reduces all-cause mortality, and CV mortality. There is a paucity of RCT data on the CV harm of non-ASA NSAIDs, but non-naproxen NSAIDs appear to offer no cardioprotection in observational studies, and may actually increase the risk of CV events. Knowledge regarding the CV harms associated with non-ASA NSAIDs and COX-2 inhibitors is in a rapid state of flux. COX-2 inhibitors appear to be associated with an increased risk of CV events.

Authors' recommendations: Screening with clinical examination or ultrasound can identify newborns at risk for DDH, but due to the high rate of spontaneous resolution of neonatal hip instability and dysplasia and the lack of evidence of the effectiveness of interventions on functional outcomes, the net benefits of screening are not clear.

Authors' methods: Review

Project Status: Completed

URL for project: http://www.ahrq.gov/clinic/serfiles.htm

Year Published: 2007

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: Agency for Healthcare Research and Quality

Contact Address: Center for Outcomes and Evidence Technology Assessment Program, 540 Gaither Road, Rockville, MD 20850, USA. Tel: +1 301 427 1610; Fax: +1 301 427 1639;

Contact Name: martin.erlichman@ahrq.hhs.gov

Contact Email: martin.erlichman@ahrq.hhs.gov

Copyright: Agency for Healthcare Research and Quality (AHRQ)