(P-617) Use of Renin-angiotensin-aldosterone System Inhibitors and the Risk of Acute Pancreatitis

Background: There are conflicting reports on the effects of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) on the incidence of acute pancreatitis. To date, the few observational studies that have been conducted on the topic had significant methodological limitations.

Objectives: To determine whether use of ACE inhibitors and ARBs is associated with incident acute pancreatitis, compared with use of dihydropyridine calcium channel blockers (dCCBs). dCCBs were selected as comparator as these drugs are used at the same disease stage than ACE inhibitors and ARBs, and have not previously been associated with acute pancreatitis.

Methods: Using the United Kingdom Clinical Research Datalink linked to the Hospital Episodes Statistics repository and Office for National Statistics, two population-based, new-user, active comparator cohorts were assembled from April 1, 1998 to December 31, 2018. The first cohort included 308,969 initiators of ACE inhibitors and 206,872 initiators of dCCBs. The second cohort included 91,729 initiators of ARBs and 313,387 initiators of dCCBs. Cox proportional hazards models were fit to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of acute pancreatitis (defined as a hospitalization with a primary diagnosis of acute pancreatitis), comparing use of ACE inhibitors and ARBs, separately, with use of dCCBs. The models were weighted using standardized mortality ratio weights that were generated from calendar time-specific propensity scores.

Results: ACE inhibitors were associated with an increased risk of acute pancreatitis, compared with dCCBs (65.1 vs. 45.7 per 100,000 person-years, respectively; HR: 1.45, 95% CI: 1.16-1.83). The HRs gradually increased with duration of use, reaching a peak after 12-24 months of use (HR: 2.12, 95% CI: 1.13-3.99). The number needed to harm after two and five years of use was 2398 and 1007, respectively. In contrast, ARBs were not associated with an increased risk of acute pancreatitis, compared with dCCBs (54.5 vs. 55.7 per 100,000 person-years, respectively; HR: 0.94, 95% CI: 0.76-1.16), with no evidence of a duration-response relationship.

Conclusions: In this large population-based study, ACE inhibitors were associated with an increased risk of acute pancreatitis compared with dCCBs. In contrast, no association was observed with ARBs.