Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and the Risk of Acute Pancreatitis: A Systematic Review and Meta-Analysis

Observational studies have evaluated the risk of acute pancreatitis associated with drugs acting on the Renin-Angiotensin-Aldosterone System (RAAS) but reported conflicting results. This meta-analysis aims to investigate the risk of acute pancreatitis associated with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). PubMed and Embase were searched for observational studies. A random-effects model was used to pool odds ratios (ORs). A sensitivity analysis explored the robustness of the initial findings according to study design, treatment duration, dose, age, active substance, and Risk of Bias scores. Main results were re-analyzed using the Knapp-Hartung method and Bayesian random-effects. Eleven observational studies were included. ACE inhibitors increased the risk of acute pancreatitis (OR 1.33; 95% CI 1.12-1.58; I² = 93%), whereas ARBs did not (OR 0.82; 95% CI 0.80-0.83; I² = 0%). Few studies presented disaggregated results for the sensitivity analyses, but most estimates were consistent with the initial findings. The Knapp-Hartung method and Bayesian random-effects meta-analyses yielded similar results. The incidence rate of acute pancreatitis among patients treated with ACE inhibitors was 0.98 cases per 1,000 person-years, while for ARBs it was 0.71 cases per 1,000 person-years. These results suggest that ACE inhibitors increase the risk of acute pancreatitis, in contrast to the effect of ARBs. Healthcare professionals should be aware of the potential risk of pancreatitis when managing patients receiving these medications.