This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Contact me when this article is cited  Related Content  • Related article  • Related letters  • Similar articles in JAMA  Topic Collections  • Nutritional and Metabolic Disorders  • Lipids and Lipid Disorders  • Cardiovascular System  • Cardiovascular Disease/ Myocardial Infarction  • Drug Therapy  • Drug Therapy, Other  • Alert me on articles by topic  Social Bookmarking   What's this?

	Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.

In Reply: Dr Parini and colleagues are critical that our article did not provide evidence that pactimibe inhibits ACAT-1 and ACAT-2. However, we could not specifically address this issue because the CAPTIVATE study was not designed for this purpose. Studies to assess enzyme specificity and pharmacodynamics are typically performed in earlier drug-development phases.

Parini et al suggest that we should have discussed the potential harmful effects of ACAT-1 inhibition. We did discuss that ACAT-1 inhibition might lead to accumulation of free cholesterol in macrophages, an effect that could lead to cell death. These properties suggest that ACAT-1 inhibitors are not beneficial as an antiatherosclerotic drug.

Parini et al also express their doubt that ACAT-2 might be up-regulated in human lesions, while they claim that evidence that ACAT-2 is functional in human lesions is lacking. We disagree; ACAT-2, in addition to ACAT-1, has been found to be expressed in fully differentiated . . . [Full Text of this Article]

Raphaël Duivenvoorden, MD
r.duivenvoorden@amc.uva.nl

Eric de Groot, MD, PhD; John J. P. Kastelein, MD, PhD
Academic Medical Center
Amsterdam, the Netherlands

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

ACAT Inhibition and Progression of Carotid Atherosclerosis in Patients With Familial Hypercholesterolemia: The CAPTIVATE Randomized Trial
Marijn C. Meuwese, Eric de Groot, Raphaël Duivenvoorden, Mieke D. Trip, Leiv Ose, Frans J. Maritz, Dick C. G. Basart, John J. P. Kastelein, Rafik Habib, Michael H. Davidson, Aeilko H. Zwinderman, Lee R. Schwocho, Evan A. Stein, and for the CAPTIVATE Investigators
JAMA. 2009;301(11):1131-1139.
ABSTRACT | FULL TEXT  

RELATED LETTERS

Carotid Atherosclerosis Progression and ACAT Inhibition
Paolo Parini, Mats Eriksson, and Lawrence L. Rudel
JAMA. 2009;302(3):255.
EXTRACT | FULL TEXT  

Carotid Atherosclerosis Progression and ACAT Inhibition
Simon Dimmitt and Gerald Watts
JAMA. 2009;302(3):255-256.
EXTRACT | FULL TEXT