Barter - Figure 14 - Why adverse outcome? Text

The failure of the first CETP inhibitor, torcetrapib, to produce benefit – indeed, it increased mortality – leads to obvious questions about mechanisms. As shown in the Figure, 3 possible explanations have been advanced (remembering always, of course, that clinical trials provide clues; they do not provide mechanisms) without much evidence.

The first possible explanation is that inhibiting CETP is pro-atherogenic; ie, unlike in rabbits, where lack of CETP is anti-atherogenic, people are different and so inhibition of CETP may be pro-atherogenic. This is possible, and at this time, we cannot exclude it on the basis of evidence.

The second possibility is that while CETP increased the concentration of HDL, that HDL was “dysfunctional.” A number of investigators have proposed this explanation, but without much evidence.

Barter P. J Clin Lipidol. 2011; 5(6).