Long-term statin use decreases the risk of gallstone disease

Clinical question Does long-term statin therapy reduce the risk of gallstone disease?

Bottom line Long-term use of statins is significantly associated with a reduced risk of gallstones followed by cholecystectomy. Long-term use of fibrates is significantly associated with an increased risk. (Level of evidence = 3b)

Synopsis By decreasing cholesterol biosynthesis, statins may reduce the risk of cholesterol gallstones. These investigators analyzed data obtained from the United Kingdom General Practice Research Database, a previously validated registry encompassing information from approximately 5 million patients cared for by general practitioners. Cases included patients 20 years or older with a first-time diagnosis of gallstone disease or cholecystectomy between 1994 and 2008. Control patients with no history of gallstone disease were matched for age, sex, general practice, and number of years of active history in the database. Lipid-lowering drug exposures were assessed using the computer record. Multivariate regressions were performed to control exposure for potential confounders including sex, age, smoking, body mass index, ischemic heart disease, estrogen use, and liver and renal disease, among others. A total of 27,035 cases (76% women; mean age = 53.4 years) were identified including 9,602 patients with cholecystectomy only and 17,433 patients with cholecystectomy after a gallstone diagnosis. Current statin use was significantly associated with a reduced risk of developing gallstones with cholecystectomy (odds ratio [OR] = 0.78; 95% CI, 0.73-0.83). There appeared to be a dose-response relationship, with adjusted ORs of 1.1 (0.95-1.27) for 1 to 4 prescriptions, 0.85 (0.77-0.93) for 5 to 19 prescriptions, and 0.64 (0.59- 0.70) for 20 or more prescriptions. Findings were similar for men and women and were not related to age. Long-term use of fibrates was significantly associated with an increased risk of gallstone disease (OR = 1.39; 1.12-1.72).

Bodmer M, Brauchli YB, Krähenbühl S, et al. Statin use and risk of gallstone disease followed by cholecystectomy. JAMA. 2009;302(18):2001-2007.