"So if this one [Dalcetrapib] bites the dust, Apabetalone is the only one left standing?"

One can't directly compare apabetalone to CETP inhibitors anymore. They have very little in common other than modulating HDL via different mechansims. So it is no longer appropriate to refer to apabetalone as the last one standing in terms of drugs modulating HDL and/or testing the HDL hypothesis. 

CETP inhibitors are a class of compounds that target a single enzyme and raises HDL-cholesterol. When apabetalone/RVX-208 was first developed, it was discovered as a pre-clinical molecule that increased the synthesis and secretion of apoAI and in earlier clinical trials was shown to be an agent that increased circulating apoAI and HDL in humans. It was at that time that CETP inhibitors and apabetalone were put in the same category.

But we've learned so much more since then. We now know that apabetalone is a BET inhibitor with selectivity for the second bromodomain. As an epigenetic "reader" of histone acetylations, BET proteins influence the expression of thousands of genes, and therefore BET inhibitors such as apabetalone affect the expression of several cardioprotective pathways via epigenetic modulation of the expression of a large list of genes. So we're not just talking about HDL and reverse cholesterol transport modulation anymore, we're bringing in inflammation, vascular calcification, complement pathway, coagulation, and effects on glucose metabolism. Those are things that apabetalone does that CETP inhibitors do not. So the commonalities between CETP inhibitors and apabetalone end at HDL-cholesterol. And even that is a weak link since they increase HDL through very different mechanisms.

Furthermore, a successful BETonMACE won't prove or disprove the HDL hypothesis because apabetalone elicits effects on many cardioprotective pathways beyond just HDL modulation. For example, look at the anti-inflammatory CANTOS trial that validated the inflammation hypothesis. BETonMACE won't be able to separate the anti-inflammatory cardioprotective effects from the HDL modulation associated cardioprotective effects.

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