Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia.
OBJECTIVE
This randomized, double-blind, placebo-controlled, parallel-group study evaluated the safety and efficacy of ezetimibe 10 mg/day in patients with primary hypercholesterolemia.


RESULTS
Following dietary stabilization, a 2-12-week washout period, and a 4-week, single-blind, placebo lead-in period, 827 patients with baseline low-density lipoprotein cholesterol (LDL-C) > or =3.36 mmol/l (130 mg/dl) to < or =6.47 mmol/l (250 mg/dl) and triglycerides < or =3.95 mmol/l (350 mg/dl) were randomized 3:1 to receive ezetimibe 10 mg or placebo orally once daily in the morning for 12 weeks. The primary efficacy endpoint was percentage reduction in direct plasma LDL-C. Ezetimibe reduced direct LDL-C by a mean of 17.7% from baseline to endpoint, compared with an increase of 0.8% with placebo (P<0.01). Response to ezetimibe was generally consistent across all subgroups analyzed. Ezetimibe also significantly improved levels of plasma total cholesterol, apolipoprotein B, high-density lipoprotein(2)-cholesterol and lipoprotein(a), and elicited a trend toward lower triglyceride levels. Ezetimibe did not alter the serum concentrations of lipid-soluble vitamins or significantly affect baseline or stimulated cortisol production. Ezetimibe was well tolerated, with a safety profile similar to that of placebo.


CONCLUSIONS
Ezetimibe, which significantly reduces LDL-C and favorably affects other lipid variables, may provide a well tolerated and effective new option for lipid management in the future.
Knopp
R H
RH
Division of Metabolism, Endocrinology & Nutrition, Northwest Lipid Research Clinic, 325 Ninth Avenue, Room 465, Box 359720, Seattle, WA 98104, USA. rhknopp@u.washington.edu
Gitter
H
H
Truitt
T
T
Bays
H
H
Manion
C V
CV
Lipka
L J
LJ
LeBeaut
A P
AP
Suresh
R
R
Yang
B
B
Veltri
E P
EP
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D003366:Cosyntropin / Q000097:blood; D004311:Double-Blind Method; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D014280:Triglycerides / Q000097:blood; D014815:Vitamins / Q000097:blood
D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D014280:Triglycerides; D014815:Vitamins; D003366:Cosyntropin; D000069438:Ezetimibe