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July 15, 2009

Carotid Atherosclerosis Progression and ACAT Inhibition

JAMA. 2009;302(3):255-257. doi:10.1001/jama.2009.1001

To the Editor: The CAPTIVATE study, by Dr Meuwese and colleagues,1 followed the Investigation of Lipid Level Management to Understand its Impact in Atherosclerosis study (ILLUMINATE, evaluating torcetrapib to increase high-density lipoprotein) and the Ezetimibe and Simvastatin in Hypercholesterolemia Regression study (ENHANCE, evaluating the cholesterol-absorption inhibitor ezetimibe, to augment statin). All 3 studies demonstrated apparent worsening of atheroma with drug therapy. CAPTIVATE is further evidence that failure to address the principal source of atherosclerosis cholesterol is not only ineffective but may worsen disease. Compared with placebo, plasma lipoproteins and carotid intima-media thickness were worsened in patients receiving an ACAT inhibitor. ACAT inhibition increases unesterified cholesterol, which in cynomolgus monkeys can deposit in intimal atheroma.2