Simvastatin with or without ezetimibe in familial hypercholesterolemia.
BACKGROUND
Ezetimibe, a cholesterol-absorption inhibitor, reduces levels of low-density lipoprotein (LDL) cholesterol when added to statin treatment. However, the effect of ezetimibe on the progression of atherosclerosis remains unknown.


METHODS
We conducted a double-blind, randomized, 24-month trial comparing the effects of daily therapy with 80 mg of simvastatin either with placebo or with 10 mg of ezetimibe in 720 patients with familial hypercholesterolemia. Patients underwent B-mode ultrasonography to assess the intima-media thickness of the walls of the carotid and femoral arteries. The primary outcome measure was the change in the mean carotid-artery intima-media thickness, which was defined as the average of the means of the far-wall intima-media thickness of the right and left common carotid arteries, carotid bulbs, and internal carotid arteries.


RESULTS
The primary outcome, the mean (+/-SE) change in the carotid-artery intima-media thickness, was 0.0058+/-0.0037 mm in the simvastatin-only group and 0.0111+/-0.0038 mm in the simvastatin-plus-ezetimibe (combined-therapy) group (P=0.29). Secondary outcomes (consisting of other variables regarding the intima-media thickness of the carotid and femoral arteries) did not differ significantly between the two groups. At the end of the study, the mean (+/-SD) LDL cholesterol level was 192.7+/-60.3 mg per deciliter (4.98+/-1.56 mmol per liter) in the simvastatin group and 141.3+/-52.6 mg per deciliter (3.65+/-1.36 mmol per liter) in the combined-therapy group (a between-group difference of 16.5%, P<0.01). The differences between the two groups in reductions in levels of triglycerides and C-reactive protein were 6.6% and 25.7%, respectively, with greater reductions in the combined-therapy group (P<0.01 for both comparisons). Side-effect and safety profiles were similar in the two groups.


CONCLUSIONS
In patients with familial hypercholesterolemia, combined therapy with ezetimibe and simvastatin did not result in a significant difference in changes in intima-media thickness, as compared with simvastatin alone, despite decreases in levels of LDL cholesterol and C-reactive protein. (ClinicalTrials.gov number, NCT00552097 [ClinicalTrials.gov].).
Kastelein
John J P
JJ
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. j.j.kastelein@amc.uva.nl
Akdim
Fatima
F
Stroes
Erik S G
ES
Zwinderman
Aeilko H
AH
Bots
Michiel L
ML
Stalenhoef
Anton F H
AF
Visseren
Frank L J
FL
Sijbrands
Eric J G
EJ
Trip
Mieke D
MD
Stein
Evan A
EA
Gaudet
Daniel
D
Duivenvoorden
Raphael
R
Veltri
Enrico P
EP
Marais
A David
AD
de Groot
Eric
E
D000328:Adult; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001384:Azetidines / Q000009:adverse effects / Q000627:therapeutic use*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000473:pathology; D014463:Ultrasonography
D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol; D019821:Simvastatin; D000069438:Ezetimibe