pactimibe and Coronary-Artery-Disease

The enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT) esterifies cholesterol in a variety of tissues. In some animal models, ACAT inhibitors have antiatherosclerotic effects.. We performed intravascular ultrasonography in 408 patients with angiographically documented coronary disease. All patients received usual care for secondary prevention, including statins, if indicated. Patients were randomly assigned to receive the ACAT inhibitor pactimibe (100 mg per day) or matching placebo. Ultrasonography was repeated after 18 months to measure the progression of atherosclerosis.. The primary efficacy variable analyzing the progression of atherosclerosis--the change in percent atheroma volume--was similar in the pactimibe and placebo groups (0.69 percent and 0.59 percent, respectively; P=0.77). However, both secondary efficacy variables assessed by means of intravascular ultrasonography showed unfavorable effects of pactimibe treatment. As compared with baseline values, the normalized total atheroma volume showed significant regression in the placebo group (-5.6 mm3, P=0.001) but not in the pactimibe group (-1.3 mm3, P=0.39; P=0.03 for the comparison between groups). The atheroma volume in the most diseased 10-mm subsegment regressed by 3.2 mm3 in the placebo group, as compared with a decrease of 1.3 mm3 in the pactimibe group (P=0.01). The combined incidence of adverse cardiovascular outcomes was similar in the two groups (P=0.53).. For patients with coronary disease, treatment with an ACAT inhibitor did not improve the primary efficacy variable (percent atheroma volume) and adversely affected two major secondary efficacy measures assessed by intravascular ultrasonography. ACAT inhibition is not an effective strategy for limiting atherosclerosis and may promote atherogenesis. (ClinicalTrials.gov number, NCT00268515.).

Topics: Cardiovascular Diseases; Cholesterol; Coronary Artery Disease; Coronary Vessels; Disease Progression; Female; Humans; Indoleacetic Acids; Male; Middle Aged; Sterol O-Acyltransferase; Treatment Failure; Ultrasonography, Interventional

Topics: Cholesterol; Coronary Artery Disease; Coronary Vessels; Disease Progression; Humans; Indoleacetic Acids; Sterol O-Acyltransferase; Treatment Failure; Ultrasonography, Interventional

Topics: Animals; Coronary Artery Disease; Humans; Indoleacetic Acids; Sterol O-Acyltransferase

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.. 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.. 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.

Topics: Adolescent; Adult; Cholesterol; Coronary Artery Disease; Coronary Disease; Coronary Vessels; Disease Progression; Double-Blind Method; Esterification; Female; Foam Cells; Humans; Indoleacetic Acids; Male; Randomized Controlled Trials as Topic; Research Design; Sterol O-Acyltransferase; Ultrasonography, Interventional