WHY IS RAISING HDL-C WITH DRUGS NOT CARDIOPROTECTIVE?

Yet another study ( HPS2-Thrive ) using niacin to raise HDL-C  turns out negative. From physiology, one would have thought that HDL-C is the good cholesterol and that high levels of HDL-C will be cardio-protective. The big pharmas have tried very hard to produce drugs to raise HDL-C as a strategy to protect the heart against atheorsclerosis. This theory seems simple, but the practical working out has proven very difficult. The clinical landscape of raising HDL-C to protect against atherosclerosis is strewn with failed studies, starting with Torcetoprib. Last year, we had a failed AIM- HIGH ( use of naicin versus statin alone ).
Yesterday, MERCK ( MSD ), announced that their study, the HPS2-Thrive ( Heart Protection Study 2 - Treatment of HDL to reduce incidence of vascular thrombosis) study also showed no benefit in the use of Naicin / laropiprant + statin versus statin alone. The primary endpoint after 4 years of follow-up were all the major MACE. Another failed study with trying to raise HDL-C.
What puzzles me is the why?
The principle is simple. LDL-C is bad for the heart, causes blockages and events. So the lower LDL-C the better. HDL-C with its reverse cholesterol transfer ability is suppose to be cardio-protective, to regress plaques and reduce atherosclerosis. So raising HDL-C should protect all of us, especially with the Apo-Milano study. However, all attempts to do this have so far failed. I believe there are still a few studies in the pipeline, using more sophisticated HDL-C raisers.
With this HPS2-Thrive study, we wonder whether it was the choice of laropiprant which negated the study. Paropiprant was added to reduce the flushing that we often see with the use of high dose Naicin. Now we realise that laropiprant does have some effects on the platelets. Could this be why? Or is it that the HDL-C protective graph of benefit, is actually curvilinear, meaning that there is a threshold and unless we raise it high enough ( above 60mg% ) we may not see the benefit, and may infact cause harm? Or is it that the HDL-C produced by pharmacological means are the fat HDL-Cs which are laden with LDL-C and not the lean, thin ones which are hungry to absorb LDL-C? There are so many questions.
I must also congratulate MSD for announcing a negative results. It has helped us to understand this HDL-C cardio-protective mechanism better. It is certainly not a simple phenomena. MSD was prepared to be ethically correct by telling us that naicin / paropiprant ( or Cordaptive ) should not be used to raise HDL-C although they have CE mark approval in Europe, but no FDA approval in the US. Thanks MSD.
So the search for a HDL-C raiser as a therapy for cardio protection goes on.