Ultimately, the results of the AIM-HIGH and HPS2- THRIVE trials may be best viewed through an apolipoproteins lens. Both trials may reinforce the following simple lesson: equivalent on-treatment apolipoprotein levels result in equivalent outcomes. In this sense, they may be, inadvertently, the closest things we have to trials testing lipid targets, rather than a test of the HDL hypothesis or a specific test of niacin. Unfortunately, these trials excluded the population most likely to benefit from a target-based trial, those with elevated levels of apoB. Given the equivalent major coronary event rates, both trials may support the idea of treating to target apolipoprotein levels using statins, niacin, and ezetimibe in varying combinations as needed to achieve target lipoprotein levels. Looking at the CETP inhibitors failures further supports the importance to target apolipoprotein levels. Although it is known that the CETP inhibitor torcetrapib failed to improve cardiovascular outcomes because of its off-target toxicity, 14 recent failure of dalcetrapib perhaps could be explained by its lack of effect on apoB and apoA1 levels. 15 The new CETP inhibitor, anacetrapib, likely has the highest probability to succeed because it lacks the toxicity of torcetrapib and has strong apoB-lowering effects besides its apoA1- raising effects.28 Finally, subgroup analyses in both AIM-HIGH and HPS2-THRIVE trials showed potential benefits of niacin in patients with high TGs levels. With calls from experts to downplay the treat to target concept and use of combination therapy in the upcoming Adult Treatment Panel IV guidelines, 29 further analysis focused on the relation of both apolipoproteins and drug exposures to outcomes in both trials may prove very timely.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine