Rectal indomethacin is protective against post-ERCP pancreatitis in high-risk patients but not average-risk patients: a systematic review and meta-analysis

Background and Aims Rectal indomethacin is a popular chemopreventive agent to help prevent post-ERCP pancreatitis (PEP). Previous meta-analyses have shown an overall protective effect for PEP in average-risk and high-risk patients. However, these meta-analyses are limited by a small number of studies. Recently, more trials have been published addressing this issue. The aim is to determine whether rectal indomethacin prevents PEP in average-risk and high-risk groups, after incorporating these new data. Methods A comprehensive search of multiple literature databases in April 2016 was performed. Human prospective randomized controlled trials with placebo controls that examined the effect of rectally administered indomethacin on the incidence of PEP were included. Results A total of 8 trials between 2007 and 2016 (n = 3778) were included. No significant publication bias existed. All studies used similar criteria to detect pancreatitis. Random effects model meta-analysis showed that the rate of PEP was significantly lower using indomethacin compared with placebo (relative risk, 0.43; 95% confidence interval, 0.28-0.65; P < .001) in high-risk patients. There was no significant statistical or clinical heterogeneity. Among average-risk patients, the rate of PEP was similar (non-significant) between the indomethacin and placebo groups (relative risk, 0.74; 95% confidence interval, 0.52-1.07; P = .115). The result of the main outcome remained robust in multiple sensitivity analyses. Conclusions Rectal indomethacin given before or after ERCP is protective against PEP in high-risk patients versus placebo; however, it is not protective in average-risk patients versus placebo.