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.
Duivenvoorden R, de Groot E, Kastelein JJP. Carotid Atherosclerosis Progression and ACAT Inhibition—Reply. JAMA. 2009;302(3):255–257. doi:https://doi.org/10.1001/jama.2009.1002
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