CETP inhibition dead part two
From a second trial looking at arterial thickness, where torcetrapib had a statistically-significant negative effect compared to Lipitor alone.
"Another possibility relates to the fact that inhibition of CETP by torcetrapib actually increases plasma levels of CETP. At a daily dose of 60 mg, torcetrapib continuously increases levels of CETP, a finding that is ascribed to an enhanced affinity of CETP for HDL.34 This complex formation (CETP–torcetrapib–HDL) is in turn associated with extreme elevations of large HDL particles, as exemplified by the substantial increase in levels of HDL2 cholesterol (157%). In this context, it is worrisome that HDL cholesterol levels were found to increase steadily over the duration of the trial (Figure 1). It can be hypothesized that these effects may interfere with one or more of the activities of HDL, which include serving as an acceptor of cellular cholesterol, inhibiting oxidation, thrombosis, and vascular inflammation, promoting endothelial repair, and protecting against apoptosis of endothelial cells.35 The possibility that HDL may have lost its antiinflammatory potential is illustrated by the observation that torcetrapib did not affect levels of C-reactive protein. In contrast, monotherapy with a similar dose of atorvastatin in patients with familial hypercholesterolemia resulted in a 45% decrease in levels of high-sensitivity C-reactive protein in a trial similar to ours in duration and size.36"
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