(A-133) Decreased Risk of Clinical Gallstone Disease in New-Users of Statins

Background: Statins lower hepatic cholesterol synthesis and serum LDL levels, which could be associated with less biliary cholesterol supersaturation and decreased gallstone formation. Prior research has yielded conflicting results about statin exposure in humans and the risk of clinical gallstone disease (cGD).

Objectives: This study aims to evaluate the impact of new statin exposure on cGD. We hypothesize that statin initiation decreases cGD risk.

Methods: This study utilized US MarketScan data (2015-2019) in an active-comparator new-user cohort design, including adults ≥18 years. In an intention-to-treat analysis, new-users of statins were compared to new-users of non-statin lipid-lowering agents (e.g., PCSK9 inhibitors). New-users of statins were also compared to new-users of ACE inhibitors (ACEIs) or Angiotensin II receptor blockers (ARBs), which lack lipid-lowering effects and are prescribed for another chronic condition. Those with prior cGD diagnoses or cholecystectomy were excluded. cGD occurrence, identified by an inpatient or outpatient claim for cholecystectomy, was assessed 1, 2, 3, 6, and 12 months after the index date, calculating relative risks (RR, 95% CI) and adjusting for age and sex.

Results: There were 1,678,378 statin (87.75%) new-users compared to 234,393 (12.25%) non-statin lipid-lowering agent new-users, and 1,678,378 (58.59%) statin new-users compared to 1,186,285 (41.41%) ACEI/ARB new-users. New-users of statins had a lower cGD risk than those initiating non-statin lipid-lowering agents in the 1-, 2-, 3-, 6-, and 12-month periods [RRs ranging from 0.29 (95% CI: 0.17–0.48) to 0.45 (0.36–0.56], with RR estimates increasing with increased time after initiation. Similarly, new-users of statins had a lower cGD risk than new-users of ACEI/ARBs at all time points [RRs ranging from 0.54 (0.36–0.82) to 0.74 (0.63–0.88)], with a similar trend of increasing RR with time after initiation.

Conclusions: New statin use was linked to a lower cGD risk, possibly due to decreased biliary cholesterol supersaturation mechanism. If validated and supported by dose, duration, and discontinuation analyses, and results are confirmed, therapeutic strategies that reduce bile cholesterol supersaturation, hepatic cholesterol synthesis, serum LDL, or inflammation could help prevent cGD and reduce the need for invasive biliary surgery.