Comparative effects of simvastatin and pravastatin on cholesterol synthesis in patients with primary hypercholesterolemia.

The effects of simvastatin and pravastatin on cholesterol biosynthesis were compared in 26 hypercholesterolemic patients who were randomly allocated to either simvastatin or pravastatin treatment (20 mg once daily) for 6 weeks in a crossover trial. Serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) lathosterol (latho) concentrations and lathosterol/cholesterol (latho/chol) ratios (the latter two are considered as reliable indices of whole body cholesterol synthesis) were evaluated at the beginning and end of each therapeutic sequence. Reductions in TC and LDL-C were more pronounced (P < 0.001) with simvastatin (TC = -28.0%, LDL-C = -35.6%) than with pravastatin (TC = -19.6%, LDL-C = -25.2%). These results were associated with concomitant decreases in both latho concentrations (-59.0% with simvastatin and -37.0% with pravastatin) and latho/chol ratios (-43.0% with simvastatin and -20.3% with pravastatin). Simvastatin resulted in more marked diminutions of latho concentrations (P < 0.01) and latho/chol ratios (P < 0.05) than pravastatin. These results suggest that the better efficacy of simvastatin on serum cholesterol and LDL cholesterol might result in part from a greater inhibitory action of simvastatin on cholesterol synthesis compared with that of pravastatin.