An observational study found that people who were long-term users of statins had a significantly lower risk of developing gallstone disease followed by cholecystectomy than non-users.

Gallstone disease is common in Western countries and is a major cause of gastrointestinal morbidity and hospital admission. Most gallstones (80-90%) are cholesterol based, thus it is feasible that drugs affecting cholesterol biosynthesis might reduce the rate of gallstone formation. This study was intended to explore the potential association further. The authors used the UK GPRD database to carry out a case-control analysis. They identified all patients aged 20 and over with a first-time diagnosis of gallstone disease followed by cholecystectomy or cholecystectomy alone between 1994 and 2008: main exclusion criteria were less than 3 years history on the database, alcohol or drug abuse, HIV disease, and cancer except non-melanoma skin cancer. Up to four controls with no history of gallstone disease were identified, based on index date, age, sex, practice, and time on the database. Exposure to statins and other lipid-lowering drugs was obtained from the same database. Primary outcome was the adjusted odds ratio (AOR) for developing gallstone disease followed by cholecystectomy in relation to exposure to lipid-lowering agents.

There were 27,035 eligible cases, matched with 106,531 matched controls (average 3.94 per patient). The majority (76%) were women, and mean age was 53.4 at the index date. Of the full study population, 11,264 (2,396 patients and 8,868 controls) were taking statins, 1,514 were taking fibrates, and 1,038 were taking other lipid-lowering agents; most of those on statins were taking these drugs only. Current statin use was associated with a significantly reduced risk of gallstone disease compared to non-users, with an AOR of 0.78 (95% CI, 0.73 to 0.83); past use was associated with an increased risk (AOR 1.19; 95% CI, 1.07 to 1.32). The reduction in risk increased with longer periods of use, from an AOR of 1.10 (95% CI, 0.95 to 1.27) for 1 to 4 current prescriptions to an AOR of 0.64 (95% CI, 0.59 to 0.70) for 20 or more current prescriptions.

Subgroup analysis by age, sex, and statin taken revealed no significant differences. In order to compare only those with hypercholesterolaemia, short-term use was compared with long-term use: in this analysis, the AOR for long-term compared to short-term use was 0.58 (95% CI, 0.50 to 0.68).

The authors conclude that in their analysis, long-term use of statins was associated with a reduced risk of gallstone disease leading to cholecystectomy, with the benefit starting to appear after about 1 to 1.5 years of use. Adjustment for major risk factors and co-morbidities did not significantly affect the results, and the association continued for those with obesity (who would be regarded as being at increased risk of gallstone disease). They discuss the strengths and limitations of the study, noting that a causal effect cannot be assumed because of its observational nature.