Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies

Abstract

Background: Ezetimibe (SCH 58235) is a novel cholesterol absorption inhibitor that selectively and potently blocks intestinal absorption of dietary and biliary cholesterol. Objective: Data from 2 multicenter, placebo-controlled, double-blind, randomized, parallel-group, 12-week studies of ezetimibe were pooled to evaluate the drug's effect on lipid parameters in patients with primary hypercholesterolemia. Methods: After dietary stabilization (National Cholesterol Education Program Step I diet or a stricter diet), washout of lipid-altering drugs, and a 6-week placebo lead-in period, patients with baseline plasma low-density lipoprotein cholesterol (LDL-C) levels ≥130 and ≤250 mg/dL and plasma triglyceride (TG) levels ≤300 mg/dL were randomized to receive either ezetimibe 0.25, 1, 5, or 10 mg, or placebo administered once daily before the morning meal in study A (dose-response study) or ezetimibe 5 or 10 mg or placebo administered once daily before the morning meal or at bedtime in study B (dose-regimen study). Results: A total of 432 patients were included in this pooled analysis, 243 in study A and 189 in study B. The 5- and 10-mg doses of ezetimibe significantly reduced LDL-C levels by 15.7% and 18.5%, respectively ( P < 0.01 vs placebo) and significantly increased high-density lipoprotein cholesterol (HDL-C) levels by 2.9% and 3.5%, respectively ( P < 0.05 vs placebo). A reduction in plasma TG levels was observed ( P = NS). With the 10-mg dose of ezetimibe, 67.8% of patients achieved ≥15% reduction in plasma LDL-C levels, and 22.0% achieved ≥25% reduction. With the 5-mg dose, 54.0% of patients achieved ≥15% reduction in plasma LDL-C levels, and 15.3% achieved ≥25% reduction. The decrease in plasma LDL-C levels was significantly greater with ezetimibe 10 mg compared with ezetimibe 5 mg ( P < 0.05). Ezetimibe was well tolerated, with an adverse event profile similar to that of placebo. Conclusions: In these two 12-week studies, ezetimibe significantly decreased plasma LDL-C levels and increased plasma HDL-C levels, with a tolerability profile similar to that of placebo.