Gallbladder disease as a side effect of drugs influencing lipid metabolism. Experience in the Coronary Drug Project.

We analyzed data obtained during the Coronary Drug Project to discover the influence of the drugs used on the frequency of gallbladder disease. Of 2680 placebo-treated men who had had myocardial infarction, gallbladder disease developed in 69. Corresponding figures for those given 2.5 mg of estrogen, 5.0 mg of estrogen and 1.8 g of clofibrate per day were 46 of 1061, 47 of 1081 and 42 of 1051, respectively. Each treatment group differed from placebo by over twice the standard error of the difference, life-table analysis yielding P less than 0.05 for each drug-placebo comparison. Forty-five variables, including age, body weight, blood pressure, serum lipids and blood sugar, were evaluated as risk factors. Age significantly correlated with prevalence of known gallbladder disease at entry (r = 0.066, P less than 0.001). No variable yielded a strong and consistent correlation with the incidence of subsequent new gallbladder disease. Gallstone formation is a risk whenever clofibrate or estrogen is prescribed.