Rectal indomethacin alone versus combined with prophylactic pancreatic duct stenting for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients: a systematic review and meta-analysis

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BACKGROUND: Postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most frequent complication of ERCP, particularly in high-risk patients. Although rectal indomethacin and prophylactic pancreatic duct stenting (PDS) independently reduce PEP risk, the incremental benefit of combining both strategies remains uncertain. This meta-analysis evaluates the effectiveness of rectal indomethacin alone versus indomethacin plus prophylactic PDS for PEP prevention in high-risk patients. METHODS: PubMed, Embase, Ovid/MEDLINE, and the Cochrane Library were searched from inception through 28 January 2026. Randomized controlled trials (RCTs) and cohort studies comparing rectal indomethacin alone with indomethacin plus prophylactic PDS in high-risk ERCP patients were included. Risk ratios with 95% confidence intervals (CI) were pooled using a random-effects model. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation framework. RESULTS: Six studies (three RCTs and three cohort studies) including 3753 patients were analyzed. Overall, PEP occurred less frequently with combination prophylaxis than with indomethacin alone (risk ratio = 0·73, 95% CI: 0·60-0·89, I2 = 9%). Reductions were also observed for mild PEP (risk ratio = 0·73, 95% CI: 0·58-0·93, I2 = 0%) and moderate-to-severe PEP (risk ratio = 0·73, 95% CI: 0·55-0·98, I2 = 0%). The protective effect on overall PEP was confirmed in analyses restricted to RCTs. Based on randomized evidence, the certainty of the evidence was moderate. CONCLUSION: In high-risk ERCP patients, adding prophylactic PDS to rectal indomethacin was associated with a reduced incidence of PEP compared with indomethacin alone.