Cyclooxygenase-2 inhibitors in colorectal cancer prevention: counterpoint.

Aspirin is the best chemoprevention agent for colorectal cancer risk reduction despite the fact that the evidence for a decrease in mortality is weak. The cyclooxygenase-2 selective agents (COXIBS) have an efficacy similar to that of aspirin for most gastrointestinal (GI) lesions but not esophagus. Specifically, there are beneficial short term effects of COXIBs on the risk of colorectal adenoma as shown in the Approve, PreSAP, and APC studies. However, there is still an increased risk of upper GI complications with COXIBs when compared with placebo, and this risk may increase further in some people when aspirin is also consumed. Whereas aspirin reduces the risk of cardiovascular events, COXIBs and most traditional nonsteroidal anti-inflammatory drugs (but not all) are both associated with an increased risk of thrombotic cardiovascular events compared with placebo. In conclusion, COXIBs have a niche role for patients with familial adenomatous polyposis. The value of aspirin remains with respect for efficacy, mainly in the esophagus, and the side effect profile, especially in the elderly if given with acid suppression therapy. COXIBs should be used in younger populations, but if they are considered in the elderly because of increased GI risks, and the cardiovascular risk is also increased, then combination treatment with aspirin and a proton-pump inhibitor should also be considered instead, such as in the ASPECT trial.