Intravascular ultrasound assessment of novel antiatherosclerotic therapies: rationale and design of the Acyl-CoA:Cholesterol Acyltransferase Intravascular Atherosclerosis Treatment Evaluation (ACTIVATE) Study.
BACKGROUND
Inhibiting the enzyme acyl-CoA:cholesterol acyltransferase (ACAT) has beneficial effects on foam cell formation and therefore has the potential to favorably influence the progression of coronary atherosclerosis. The aim of this study is to determine whether ACAT inhibition, when added to usual medical care, reduces atheroma progression in subjects with coronary artery disease.


METHODS
Five hundred thirty-four subjects with established coronary artery disease on angiography were randomized to receive the experimental ACAT inhibitor, pactimibe, 100 mg daily or matching placebo for 18 months. The primary efficacy parameter will be the nominal change in percent atheroma volume determined by analysis of pullback intravascular ultrasound (IVUS) images of matched coronary artery segments acquired at baseline and 18-month follow-up. In addition, the effect of pactimibe on plasma lipids and inflammatory markers and the incidence of clinical cardiovascular events will also be assessed.


CONCLUSIONS
Serial IVUS has emerged as a sensitive imaging modality to assess the impact that novel antiatherosclerotic strategies have on the arterial wall. In this study, IVUS will be used to assess whether ACAT inhibition modifies progression of atherosclerotic plaque.
Nicholls
Stephen J
SJ
Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Sipahi
Ilke
I
Schoenhagen
Paul
P
Wisniewski
Lisa
L
Churchill
Tammy
T
Crowe
Timothy
T
Goormastic
Marlene
M
Wolski
Kathy
K
Tuzcu
E Murat
EM
Nissen
Steven E
SE
D000293:Adolescent; D000328:Adult; D002784:Cholesterol / Q000378:metabolism; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000517:prevention & control*; D003327:Coronary Disease / Q000188:drug therapy*; D003331:Coronary Vessels / Q000000981:diagnostic imaging*; D018450:Disease Progression; D004311:Double-Blind Method; D004951:Esterification; D005260:Female; D005487:Foam Cells / Q000187:drug effects; D006801:Humans; D007210:Indoleacetic Acids / Q000627:therapeutic use*; D008297:Male; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*; D018084:Ultrasonography, Interventional
D007210:Indoleacetic Acids; D002784:Cholesterol; C509302:pactimibe; D002785:Sterol O-Acyltransferase