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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

Hypercholesterolemia is a robust predictor of atherosclerosis, and hydroxyl-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are effective in reducing clinical arterial disease and mortality.³ The efficacy of drugs other than statins appears limited, particularly with respect . . . [Full Text of this Article]

Simon Dimmitt, BMedSc(Hons), FRACP
sdimmitt@bigpond.com

Gerald Watts, DSc, FRCP(Lond)
School of Medicine and Pharmacology
University of Western Australia
Perth, Australia

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RELATED ARTICLE

ACAT Inhibition and Progression of Carotid Atherosclerosis in Patients With Familial Hypercholesterolemia: The CAPTIVATE Randomized Trial
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