Cholesterol synthesis inhibitors in cholesterol gallstone disease

Cholesterol synthesis inhibitors (HMG-CoA Reductase Inhibitors) are reported to decrease cholesterol saturation index of duodenal bile in hypercholesterolaemic subjects. The dissolution of gallstones in animals on treatment with these drugs created expectations of a therapeutical role for these drugs in cholesterol gallstone disease. However, in prospective studies with these drugs in humans, no effect on number and size of cholesterol gallstones was observed. This is likely the result of the fact that not just biliary secretion of cholesterol is decreased during treatment with these drugs in cholesterol gallstone disease, but phospholipids and bile salts as well. As a consequence, nucleation time of cholesterol crystals in gallbladder bile is not influenced by these drugs. Another important determinant in cholesterol gallstone disease, e.g. gallbladder motility, is not influenced by HMG-CoA reductase inhibitors. Although these drugs and their metabolites are secreted into the bile, they do not influence biliary lithogenicity. In conclusion, there seems to be no therapeutic role for HMG-CoA reductase inhibitors in the treatment of cholesterol gallstone disease, although no negative effects on determinants of cholesterol gallstone formation during treatment with these drugs are observed either.