Negative Findings for ACAT Inhibition

Inhibition of acyl–coenzyme A:cholesterol acyltransferase (ACAT), an enzyme that esterifies cholesterol, may prevent the transformation of macrophages into foam cells and interfere with the development of atherosclerosis. Although animal studies have produced mixed results, investigators conducted a manufacturer-sponsored phase 3 study of the effect of pactimibe, a nonselective ACAT inhibitor, on atherosclerosis progression.

Eligible subjects, 534 people with indications for coronary angiography and at least one vessel with stenosis ≥20%, were randomized to receive pactimibe (100 mg) or placebo daily for 18 months, in addition to usual care (including statins in 78%). Plaque progression was assessed at baseline and at 18 months by intravascu…