Comparison of ezetimibe plus simvastatin versus simvastatin monotherapy on atherosclerosis progression in familial hypercholesterolemia. Design and rationale of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial.
BACKGROUND
Lipid lowering through statin therapy significantly reduces the risk of cardiovascular events. The ENHANCE study is an international 2-year, randomized, double-blind, controlled trial designed to test the hypothesis that treatment of hypercholesterolemia by use of 2 complementary agents, ezetimibe (a specific cholesterol absorption inhibitor) and simvastatin (a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor), will result in larger beneficial effects on carotid artery intima-media thickness (CA IMT) than simvastatin monotherapy.


METHODS
The study will recruit 725 men and women with heterozygous familial hypercholesterolemia. After a placebo washout period, participants are randomized to receive daily administration of either simvastatin 80 mg and ezetimibe 10 mg or simvastatin 80 mg and placebo. The ENHANCE trial uses novel state-of-the-art single-frame digital image acquisition and rigorous quality assurance and control.


RESULTS
The primary end point is mean change from baseline to 2 years in CA IMT, using composite measures from the right and left far wall common carotid artery, carotid bulb, and internal carotid artery. Secondary end points include (1) the proportion of participants who exhibit reductions in CA IMT, (2) the change in maximum far wall IMT, (3) the proportion of participants who develop new carotid artery plaques, and (4) the changes in carotid plus common femoral artery IMT.


CONCLUSIONS
This study addresses the question of whether a regimen that uses drugs with different mechanisms of action will be of further benefit in terms of atherosclerosis reduction compared to statin monotherapy.
Kastelein
John J P
JJ
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. e.vandongen@amc.uva.nl
Sager
Philip T
PT
de Groot
Eric
E
Veltri
Enrico
E
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D019821:Simvastatin / Q000627:therapeutic use*; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D014463:Ultrasonography
D000924:Anticholesteremic Agents; D001384:Azetidines; D019821:Simvastatin; D000069438:Ezetimibe