Long-term Statin Use and the Risk of Gallstone Disease: A Population-based Case-Control Study

Abstract

Most gallstones originate from cholesterol-supersaturated bile. Statins inhibit hepatic cholesterol biosynthesis and therefore may reduce the risk of gallstone disease. Population-based evidence, however, is sparse. Thus, the authors conducted a population-based case-control study using medical databases from northern Denmark (1.7 million inhabitants) to identify 32,494 cases of gallstones occurring between 1996 and 2008 and to identify age-, sex-, and county-matched population controls for each case. Cases and their matched controls who were exposed to lipid-lowering drugs were categorized as current users if their last prescription was redeemed ≤90 days before the case's diagnosis date; otherwise, they were categorized as former users. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals for gallstone disease in patients treated with lipid-lowering drugs. In current users, the adjusted odds ratios associating statin use with the occurrence of gallstone disease were 1.17 (95% confidence interval (CI): 1.06, 1.30) for those who had 1-4 prescriptions, 0.89 (95% CI: 0.80, 0.97) for those who had 5-19 prescriptions, and 0.76 (95% CI: 0.69, 0.84) for those who had ≥20 total prescriptions. In former users, the corresponding adjusted odds ratios were 1.24 (95% CI: 1.11, 1.39), 0.97 (95% CI: 0.86, 1.10), and 0.79 (95% CI: 0.64, 0.97), respectively. The use of other lipid-lowering drugs showed no similar association.

Declining Cholecystectomy Rate During the Era of Statin Use in Finland: A Population-Based Cohort Study Between 1995 and 2009

“…About 25% of diabetic patients have gallstone disease, and every fifth of the patients come into cholecystectomy (12). Long-term use of statins may be associated with decreased rate of cholelithiasis (13). The cardiac, pulmonary, and metabolic comorbidities commonly observed in morbidly obese patients may affect the outcome of gallbladder surgery.…”

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].…”

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].…”