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July 15, 2009

Carotid Atherosclerosis Progression and ACAT Inhibition—Reply

JAMA. 2009;302(3):255-257. doi:10.1001/jama.2009.1002

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.