Effect of ezetimibe coadministration with simvastatin in a Middle Eastern population: a prospective, multicentre, randomized, double-blind, placebo-controlled trial.
OBJECTIVE
To assess the efficacy and safety of ezetimibe coadministered with simvastatin in patients with primary hypercholesterolaemia and coronary artery disease (CAD).


METHODS
Prospective, multicentre, randomized, double-blind, placebo-controlled trial conducted in three Middle Eastern countries.


METHODS
Patients with known CAD, who were being treated with simvastatin 20 mg and had low-density lipoprotein cholesterol (LDL-C) concentrations of 2.6 to 4.1 mmol/l, were randomized to receive daily coadministration of ezetimibe 10 mg or placebo.


METHODS
The primary outcome was percentage reduction of LDL-C after 6 weeks of randomization. Secondary endpoints included number of patients who achieved National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C level and safety and tolerability.


RESULTS
We enrolled 144 patients of whom 120 had blood available for final analysis. The coadministration of ezetimibe with ongoing simvastatin therapy resulted in a statistically significant additional reduction in LDL-C concentration as compared with simvastatin monotherapy (-26.7 versus -9.1%, respectively; total additional reduction of 17.6%, P < 0.0001). More patients in the ezetimibe and simvastatin group achieved NCEP ATP III LDL-C target levels than in the simvastatin monotherapy group (70 versus 33%, respectively; P = 0.0001). The coadministration of ezetimibe with simvastatin was well tolerated with a safety profile similar to that of simvastatin monotherapy.


CONCLUSIONS
When coadministered with simvastatin therapy, ezetimibe resulted in significant additional reduction in LDL-C and enabled more patients to achieve NCEP ATP III LDL-C target levels. This was achieved safely and with excellent tolerability.
Department of Medicine, Faculty of Medicine, Kuwait University, Division of Cardiology, Mubarak Al-Kabeer Hospital, Jabriya, Kuwait.
Mohammad
M
Zubaid
Douraid K
DK
Shakir
Nooshin
N
Bazargani
Azan
A
Binbrek
Raj
R
Gopal
Omar
O
Al-Tamimi
Sherif
S
Bakir
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008877:Middle East; D011446:Prospective Studies; D019821:Simvastatin / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D001384:Azetidines; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D000069438:Ezetimibe