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Description of the Evidence

Cardiovascular Risks Associated With Celecoxib and Rofecoxib Dose/Drugs continued...

The NSAID piroxicam, at a dose of 20 mg/day, reduced mean rectal prostaglandin concentration by 50% in individuals with a history of adenomas.[50] Several studies assessing the effect of ASA or other nonsteroidals on polyp recurrence following polypectomy are in progress.[51] In several of these studies, mucosal prostaglandin concentration is being measured.

The potential for the use of NSAIDs as a primary prevention measure is being studied. There are, however, several unresolved issues that mitigate against making general recommendations for their use. These include a paucity of knowledge about the proper dose and duration for these agents, and concern about whether the potential preventive benefits such as a reduction in the frequency or intensity of screening or surveillance could counterbalance long-term risks such as gastrointestinal ulceration and hemorrhagic stroke for the average-risk individual.[52]

Aspirin

The preponderance of evidence from both observational studies and long-term follow-up of RCTs indicates that daily ASA for at least 5 years reduces the incidence of CRC. Among a group of more than 600,000 adults enrolled in an American Cancer Society study, mortality in regular users of ASA was about 40% lower for cancers of the colon and rectum.[53,54] In a report from the Health Professionals Follow-up Study of 47,000 males, regular use of ASA (at least 2 times per week) was associated with a 30% overall reduction in CRC, including a 50% reduction in advanced cases.[55] In a Women's Health Study of a randomized 2 x 2 factorial trial of 100 mg of ASA every other day for an average of 10 years, similar rates of breast, colorectal, or other site-specific cancers were observed in both the ASA and placebo arms.[56] In a report from the Nurses' Health Study involving 82,911 women followed for 20 years, the multivariate RR for colon cancer was 0.77 (95% CI, 0.67–0.88) among women who regularly used ASA (≥2 standard 325-mg tablets per week) compared with nonregular use. Significant RR was not observed, however, until more than 10 years of use. The benefit appeared to be dose-related (e.g., women who used more than 14 ASA per week for longer than 10 years had a multivariate RR for cancer of 0.47 [95% CI, 0.31–0.71]).

A systematic review of 46 observational studies of ASA and CRC in 2007 found a reduction in CRC (OR for any use 0.80 [0.73–0.87]).[57] A large cohort study (301,240 people with 3,894 colorectal cancer cases) published after this systematic review found an association between weekly or daily ASA use and reduced 10-year incidence of distal and rectal (but not proximal) colorectal cancer, with an HR of 0.76 (95% CI, 0.64–0.90) for rectal cancer for daily use. However, use was assessed at only one time, and there is no information about dose or duration of use.[37]

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