Double-dose pravastatin versus add-on ezetimibe with low-dose pravastatin - effects on LDL cholesterol,cholesterol absorption,and cholesterol synthesis in japanese patients with hypercholesterolemia (PEAS study)

Aim: this study compared the effect of doubling the dose of pravastatin with that of adding ezetimibe to low-dose pravastatin on the ldl cholesterol (ldl-c) level and on cholesterol absorption and synthesis markers. the tolerability of the 2 regimens was also compared. methods: this was a multicenter,open-label,parallel-group trial. subjects were aged from 20 to 74 years and had an ldl-c ≥120 mg/dl despite pravastatin therapy at 5-10 mg/day. they were randomly allocated to receive either add-on ezetimibe (10 mg/day) or double-dose pravastatin,and follow- up was performed for 12 weeks. the primary endpoints were the changes of ldl-c and apolipoprotein (apo) b levels after 12 weeks of treatment. cholesterol absorption and synthesis markers were also determined. results: ldl-c and apo b decreased by 16% and 14% in the ezetimibe add-on group versus 5.9% and 4.4%,respectively,in the pravastatin double-dose group. the between-group differences of these decreases were highly significant. cholesterol absorption markers (sitosterol,campesterol,and cholestanol) were reduced by 48%,36%,and 10%,respectively,in the ezetimibe add-on group,and were increased by 17%,14%,and 6%,respectively,in the pravastatin double-dose group. lathosterol (a cholesterol synthesis marker) increased by 76% in the ezetimibe add-on group and by 24% in the pravastatin double-dose group. the difference was statistically significant. no serious adverse effect was observed in either group. conclusions: adding ezetimibe to low-dose pravastatin achieves greater decreases in ldl-c,apo b,and cholesterol absorption markers than doubling the dose of pravastatin.