The Role of Aspirin in the Prevention of Polyp Recurrence: What is the Right Dose?

Large cohort studies have demonstrated efficacy of aspirin for cardiovascular disease prevention. Aspirin and other NSAIDs inhibit cyclooxygenase-2 (COX-2), a mediator of prostaglandin production. Nonselective (sulindac) and selective COX-2 inhibitors ( celecoxib, rofecoxib) induced regression of adenomas in familial adenomatous polyposis, with dose-dependent efficacy in one such trial. Randomized, controlled trials of patients with previous adenoma or colorectal cancer have shown significant efficacy at daily aspirin doses of 81 to 325 mg/d, although lowest effective aspirin dose was not clearly established. Cohort studies have underscored the need for very long-term (> 10 years) use of aspirin to reduce rates of colorectal cancer. Confounders included intermittent and variable dosing and the use of other NSAIDs and risk modifying drugs, so no clear aspirin dosing message has come from cohort studies. The randomized, controlled trials and cohort studies have taken place during a time when NSAID drug safety has come under challenge. Adverse cardiovascular events in the selective COX-2 inhibitor trials in nonfamilial adenomas have forced reexamination of the safety of NSAIDs in general. New studies will have to balance efficacy and safety more than ever.