Statin Use and Risk of Gallstone Disease Followed by Cholecystectomy

Abstract

Context Gallstone disease is a leading cause of morbidity in western countries and carries a high economic burden. Statins decrease hepatic cholesterol biosynthesis and may therefore lower the risk of cholesterol gallstones by reducing the cholesterol concentration in the bile. Data on this association in humans are scarce. Objective To study the association between the use of statins, fibrates, or other lipidlowering agents and the risk of incident gallstone disease followed by cholecystectomy. Design, Setting, and Participants Case-control analysis using the UK-based General Practice Research Database. Incident patients between 1994 and 2008 and 4 controls per each patient were identified and matched on age, sex, general practice, calendar time, and years of history in the database. The study population was 76% women and the mean (SD) age was 53.4 (15.0) years at the index date. Conditional logistic regression was used to estimate the odds ratio (OR) of developing gallstones followed by cholecystectomy in relation to exposure to lipid-lowering agents, stratified by exposure timing and duration. The ORs and 95% confidence intervals (CIs) were adjusted for smoking, body mass index, ischemic heart disease, stroke, and estrogen use. Main Outcome Measure The adjusted OR (AOR) for developing gallstone disease followed by cholecystectomy in relation to exposure to lipid-lowering agents. Results A total of 27 035 patients with cholecystectomy and 106 531 matched controls were identified, including 2396 patients and 8868 controls who had statin use. Compared with nonuse, current statin use (last prescription recorded within 90 days before the first-time diagnosis of the disease) was 1.0% for patients and 0.8% for controls (AOR, 1.10; 95% CI, 0.95-1.27) for 1 to 4 prescriptions; 2.6% vs 2.4% (AOR, 0.85; 95% CI, 0.77-0.93) for 5 to 19 prescriptions, and 3.2% vs 3.7% (AOR, 0.64; 95% CI, 0.59-0.70) for 20 or more prescriptions. The AORs for current use of statins defined as 20 or more prescriptions were similar (around 0.6) across age, sex, and body mass index categories, and across the statin class. Conclusion Long-term use of statins was associated with a decreased risk of gallstones followed by cholecystectomy.

Limits and perspective of oral therapy with statins and aspirin for the prevention of symptomatic cholesterol gallstone disease

“…Epidemiological studies have demonstrated that longterm oral therapy with statins reduces the risk of symptomatic gallstones disease [7,8]. Recent articles have proposed the therapeutic use of statins for the medical treatment of cholesterol gallstones [14].…”

“…Recent epidemiological studies have reported that patients with long-term statin use have a reduced risk of gallstones disease followed by cholecystectomy [8]. This effect was statistically evident among current statin users with five or more prescriptions (1 --2 years of statin use) or among former statin users with 20 or more prescriptions [7,8].…”

“…Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme of liver cholesterol biosynthesis [7,8]. The effect of various statins on gallstone disease is still under debate: some authors have reported diminished gallstones formation and decreased concentration of cholesterol in bile or gallstone dissolution; others have not found these results [3,8].…”

“…The effect of various statins on gallstone disease is still under debate: some authors have reported diminished gallstones formation and decreased concentration of cholesterol in bile or gallstone dissolution; others have not found these results [3,8]. Recent epidemiological studies have reported that patients with long-term statin use have a reduced risk of gallstones disease followed by cholecystectomy [8]. This effect was statistically evident among current statin users with five or more prescriptions (1 --2 years of statin use) or among former statin users with 20 or more prescriptions [7,8].…”

Author's reply: statins and cholesterol gallstones: what we know, thought we knew and hope to gain

“…Human studies have shown potential benefit of statins in treating cholesterol gallstones [2,3]. A summary of the mechanisms involved have been reviewed by Ahmed et al [4].…”