Key result
Celecoxib 800 mg/day significantly reduced the recurrence of colorectal adenomas (RR 0.61; 95% CI 0.45-0.83), followed by celecoxib 400 mg/day, low-dose aspirin, and calcium.
Why the study?
Do chemopreventive agents reduce the recurrence of colorectal adenomas in patients with a history of colorectal cancer or adenomas?
Meta-Analysis (n=12,625)
Do chemopreventive agents reduce the recurrence of colorectal adenomas in patients with a history of colorectal cancer or adenomas?
Relative Risk: 0.61 (95% CI 0.45–0.83)
Celecoxib, low-dose aspirin, and calcium significantly reduce the risk of colorectal adenoma recurrence, though the cardiovascular and gastrointestinal risks of COX-2 inhibitors warrant consideration of agents with better benefit-to-risk ratios like aspirin and calcium.
Celecoxib most effectively reduces adenoma recurrence; extends NMA evidence but favors aspirin or calcium given COX-2 risks.
BACKGROUND: Protective effects of several chemopreventive agents (CPAs) against colorectal adenomas have been well documented in randomized controlled trials (RCTs); however, there is uncertainty regarding which agents are the most effective. METHODS: We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. We performed both pairwise analysis and network meta-analysis (NMA) of RCTs to compare the effects of CPAs on the recurrence of colorectal adenomas (primary outcome). Using NMA, we ranked CPAs based on efficacy. RESULTS: We identified 20 eligible RCTs enrolling 12,625 participants with a history of colorectal cancer or adenomas who were randomly assigned to receive either a placebo or one of 12 interventions. NMA using all trials demonstrated that celecoxib 800 mg/day (relative risk [RR] 0.61, 95% confidence interval [CI] 0.45-0.83), celecoxib 400 mg/day (RR 0.70, 95% CI 0.55-0.87), low-dose aspirin (RR 0.75, 95% CI 0.59-0.96) and calcium (RR 0.81, 95% CI 0.69-0.96) were significantly associated with a reduction in the recurrence of any adenomas. NMA results were consistent with those from pairwise meta-analysis. The evidence indicated a high (celecoxib), moderate (low-dose aspirin) and low (calcium) Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality. NMA ranking showed that celecoxib 800 mg/day and celecoxib 400 mg/day were the best CPAs, followed by low-dose aspirin and calcium. Considering advanced adenoma recurrence, only celecoxib 800 mg/day and celecoxib 400 mg/day were demonstrated to have a protective effect (RR 0.37, 95% CI 0.27-0.52 vs RR 0.48, 95% CI 0.38-0.60, respectively). CONCLUSION: The available evidence from NMA suggests that celecoxib is more effective in reducing the risk of recurrence of colorectal adenomas, followed by low-dose aspirin and calcium. Since cyclooxygenase-2 (COX-2) inhibitors (eg, celecoxib) are associated with important cardiovascular events and gastrointestinal harms, more attention is warranted toward CPAs with a favorable benefit-to-risk ratio, such as low-dose aspirin and calcium.
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Veettil et al. (2017) conducted a meta-analysis in History of colorectal cancer or adenomas (n=12,625). Chemopreventive agents (e.g., celecoxib) vs. Placebo was evaluated on Recurrence of colorectal adenomas (RR 0.61, 95% CI 0.45-0.83). Celecoxib 800 mg/day significantly reduced the recurrence of colorectal adenomas (RR 0.61; 95% CI 0.45-0.83), followed by celecoxib 400 mg/day, low-dose aspirin, and calcium.
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