Key result
In E3L.CETP mice, combination therapy with torcetrapib and atorvastatin did not reduce atherosclerosis compared with atorvastatin alone and resulted in lesions of a more inflammatory phenotype.
Why the study?
Does torcetrapib alone or in combination with atorvastatin reduce atherosclerosis and alter plaque phenotype in E3L.CETP mice?
Population
Humanized APOE*3-Leiden.CETP (E3L.CETP) mice fed a cholesterol-rich diet
Comparison
Torcetrapib, atorvastatin, or combination of… vs Cholesterol-rich diet without drugs
Design
Preclinical
Follow-up
14 weeks
Authors
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Provides potential mechanism for torcetrapib failure; hypothesis-generating for CETP inhibition effects on human plaque stability.
Does torcetrapib alone or in combination with atorvastatin reduce atherosclerosis and alter plaque phenotype in E3L.CETP mice?
p-value: p=<0.05
Torcetrapib does not provide additional antiatherogenic benefits over atorvastatin and induces a more inflammatory, less stable plaque phenotype in mice, providing a potential mechanism for its clinical failure.
Haan et al. (2008) studied Atherosclerosis. Torcetrapib and atorvastatin vs. No drugs or atorvastatin alone was evaluated on Atherosclerotic lesion size (p=<0.05). In E3L.CETP mice, combination therapy with torcetrapib and atorvastatin did not reduce atherosclerosis compared with atorvastatin alone and resulted in lesions of a more inflammatory phenotype.
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