Safety and Effectiveness of Non-Steroidal Anti-Inflammatory Drugs used to Prevent Post-ERCP Pancreatitis in High-Risk Populations: An Observational Cohort Study

Abstract

Endoscopic retrograde cholangiopancreatography (ERCP) is a common procedure for managing disorders of the pancreatic and/or biliary system(s). Though effective, ERCP is complicated by post-ERCP pancreatitis (PEP) in 5-15% of cases. Administration of a single rectal dose of a non-steroidal anti-inflammatory drug (NSAID) at the time of ERCP reduces the risk of PEP by 30-50%. However, NSAIDs are known to have adverse effects on the kidneys after prolonged use and are often not recommended in patients 65 and older and those with chronic kidney disease (CKD). Little is currently known about the potential renal harms associated with single-dose NSAIDs in the setting of medical procedures such as ERCP. We report on relevant post-ERCP renal outcomes including acute kidney injury (AKI) and acute kidney disease (AKD) in at-risk patients who received single-dose peri-procedural NSAIDs compared to those who did not, assessing for effect modification and differences in the association stratified by higher-risk subgroups, namely (1) patients 65 years of age and older versus those less than 65 years of age (n = 5,885 and n = 5,310, respectively) and (2) patients with and without pre-existing CKD (n=757 and n=10,438, respectively). Multivariable logistic regression models were developed to adjust for clinically relevant patient- and procedure-related variables. In the analyzed cohort of 11,195 patients, there was no statistically significant association between NSAIDs and AKI (aOR 0.53 (0.22, 1.26)) or AKD (aOR 0.53 (0.25, 1.10)). There was no evidence of effect modification by age (p=0.83) or by CKD (p=0.72) in the model for AKI; likewise, there was no evidence of effect modification in the model for AKD (for either age, p=0.22, or CKD, p=0.49). In conclusion, single-dose NSAIDs around the time of ERCP were not associated with clinically relevant adverse changes in renal function in the overall population nor was there evidence of effect modification by age or CKD status, and as such there were no differences in these associations within high-risk subgroups. By demonstrating that there is no association between short term exposure to NSAIDs for ERCP and adverse renal events, we hope to inform clinical practice guidelines advising on their use.