Conclusion
Although two members of the CETP inhibitor drug family have clearly been removed from the drugs cabinet, it is still a fact that we do not know if the remaining members will provide a clinical benefit for patients with CVD/CHD. The two members of this family under clinical investigation, currently in Phase III randomised control trials (Anacetrapib: REVEAL; NCT01252953 and Evacetrapib: ACCELERATE; NCT01687998), are due to report in 2016/17. Results from these highly powered, multi-centre studies, will determine the success or failure of the original hypothesis that CETP inhibition is of benefit to CVD/CHD. Any chance of addressing whether success is through raising HDL-C per se is lost following the failure of Dalcetrapib, the only member of the family that had little effect of plasma LDL-C. Efficacy of either CETP inhibitor remaining in the arena, may be due to the ability of one or other of these drugs to further reduce plasma LDL-C, rather than a benefit of raising HDL-C concentration. Should the drugs fail to give a beneficial effect, the reasons will be largely unknown, but may relate to the altered kinetic of the dynamic effects that increase the circulating half-life and hence complexity of the HDL particles. The results of these studies are anticipated with gathering interest, and an additional benefit will be that they will provide an important opportunity to gain a further understanding of HDL metabolism/catabolism in disease, which will be invaluable in progressing with clinical development of these compounds.