Risk of Acute Pancreatitis Associated With ARBs and ACE Inhibitors: A Meta-Analysis of Observational Studies

OBJECTIVES: Several observational studies evaluated the risk of acute pancreatitis associated with drugs acting in the Renin–Angiotensin–Aldosterone System, but the results are conflicting.^[1-4] This meta-analysis is aimed at investigating the risk of acute pancreatitis associated with two classes of Renin-Angiotensin-Aldosterone System inhibitors, the Angiotensin-converting enzyme (ACE) inhibitors and the Angiotensin II receptor blockers (ARBs).

METHODS: PUBMED and EMBASE were searched from their inception to May 4th, 2043, to identify cohort and case-control studies evaluating the risk of acute pancreatitis associated with either ACE inhibitors or ARB. A meta-analysis using a random-effects model was performed to pool odds ratios (ORs) with their 95% confidence intervals (CIs). Between-studies heterogeneity was assessed using the I² statistics. A sensitivity analysis was conducted to explore the robustness of the initial findings, using two additional methods: a) the Knapp-Hartung method in combination with the Paule-Mandel estimator for the between-study variance; b) a bayesian random-effects meta-analysis.

RESULTS: Nine observational studies were retrieved from the literature search, 8 reporting results for ACE inhibitors and 5 reporting results for ARB. According to the initial analysis, ACE inhibitors increase the risk of acute pancreatitis (OR 1.41; 95% CI 1.14 – 1.76; I² = 87%), but not ARBs (OR 0.78; 95% CI 0.71 – 0.87; I² = 87%). Reanalysis of the data according to the Knapp-Hartung method did not significantly change the initial findings. The results reported by the bayesian meta-analyses identified an increased risk of acute pancreatitis associated with ACE inhibitors [OR 1.40; 95% credible interval (CrI) 1.04 – 1.87), but not with ARBs (OR 0.80; 95% CrI 0.52 – 1.23).

CONCLUSIONS: The results from this meta-analysis suggest ACE inhibitors increase the risk of acute pancreatitis, confirming the results reported by some observational studies published over the years. No increased risk was found for ARBs.