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Effects of chemopreventive agents on the incidence of recurrent colorectal adenomas: a systematic review with network meta-analysis of randomized controlled trials

Authors Veettil SK, Teerawattanapong N, Ching SM, Lim KG, Saokaew S, Phisalprapa P, Chaiyakunapruk N

Received 10 November 2016

Accepted for publication 15 March 2017

Published 23 May 2017 Volume 2017:10 Pages 2689—2700


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Faris Farassati

Sajesh K Veettil,1 Nattawat Teerawattanapong,2 Siew Mooi Ching,3,4 Kean Ghee Lim,5 Surasak Saokaew,6–9 Pochamana Phisalprapa,10 Nathorn Chaiyakunapruk7,8,11,12

1School of Pharmacy/School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia; 2Division of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, Thailand; 3Department of Family Medicine, Faculty of Medicine and Health Sciences, 4Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, 5Clinical School, Department of Surgery, International Medical University, Seremban, Negeri Sembilan, 6Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Phayao, 7School of Pharmacy, Monash University Malaysia, Selangor, Malaysia; 8Centre of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand; 9Unit of Excellence on Herbal Medicine, School of Pharmaceutical Sciences, University of Phayao, Thailand; 10Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 11School of Pharmacy, University of Wisconsin, Madison, USA; 12Health and Well-being Cluster, Global Asia Platform in the 21st Century (GA21) Platform, Monash University Malaysia, Selangor, Malaysia

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.

Keywords: colorectal adenomas, chemoprevention, systematic review, meta-analysis, network meta-analysis, randomized controlled trials

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