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.