Review questions whether CETP inhibitors remain a viable therapeutic approach after a major trial failure (Cardiovasc Ther 2008)

The recent failure of a major inhibitor of the cholesterol ester transfer protein (CETP), in trials on high-risk coronary patients, indicated that potentially this therapeutic target might not be a viable one. This conclusion is, however, not surprising since evaluating prior knowledge, the rationale of this therapeutic approach appears to be extremely weak. Although raising high-density lipoprotein (HDL) by a variety of pharmaceutical approaches may still provide a desirable target, CETP inhibitory treatment has very little to offer. Analysis of the literature pertaining to the CETP approach, epidemiological data on individuals with CETP mutations, and finally and in-depth analyses of pharmacological interventions, all appear to indicate that CETP inhibitory treatment should not be pursued as a viable approach. In addition, some of the findings from the clinical studies, for example, in particular a dramatic rise of infectious complications, cast significant perplexity on the possibility of convincing health authorities on the clinical safety of CETP inhibitors. Potentially CETP stimulation, for example by probucol or derivatives may provide instead a more satisfactory approach to cardiovascular prevention.