THE EFFECTS OF THE 3-HYDROXY, 3-METHYLGLUTARYL COENZYME-A REDUCTASE INHIBITOR PRAVASTATIN ON BILE COMPOSITION AND NUCLEATION OF CHOLESTEROLCRYSTALS IN CHOLESTEROL GALLSTONE DISEASE

3-hydroxy,3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors r educe biliary cholesterol saturation index (CSI) in duodenal bile in h ypercholesterolemic patients and might be useful for gallstone dissolu tion. However, preliminary data suggest that these drugs are not effec tive in this respect. We therefore studied 33 patients with radiolucen t gallstones in an opacifying gallbladder who were scheduled for elect ive cholecystectomy. Patients were treated with 40 mg pravastatin day( -1) or placebo during the 3 weeks before surgery, Six patients could n ot be evaluated. Baseline characteristics (age, sex, body mass index, serum cholesterol, and the solitary/multiple gallstone ratio) were sim ilar in both groups, Serum cholesterol fell by 39% in the pravastatin group (P < .001) and remained unchanged in the placebo group, Biliary cholesterol (9.5 +/- 1.3 vs. 14.3 +/- 1.5 mmol/L, P = .026), and phosp holipid concentrations (24.8 +/- 3.9 vs. 36.7 +/- 3.9 mmol/L, P = .043 ) were lower in the pravastatin group. Although bile salt concentratio ns were lower in the pravastatin group (114 +/- 21 vs. 152 +/- 15 mmol /L), this difference was not significant, CSI was not different betwee n both groups (142 +/- 27% [pravastatin] vs. 113 +/- 6% [placebo], P = NS). Cholesterol crystals were present in fresh bile in 7 of 13 patie nts in the pravastatin group and in 11 of 14 controls (P = NS). Nuclea tion time was comparable between the 2 groups (13 +/- 3 vs, 9 +/- 3 da ys, P = NS). Bile salt species and molecular species of phospholipids determined with high-performance liquid chromatography did not differ either between both groups, Not only cholesterol but also phospholipid concentrations decrease in gallbladder bile during pravastatin treatm ent in cholesterol gallstone patients, with comparable CSI and nucleat ion time. This study does not support the use of HMG-CoA reductase inh ibitors for dissolution of cholesterol gallstones.