"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."

Just to take the anti-inflammatory issue a step further, last week Dr. Steven Nissen gave an AMAZING talk at the Esperion Investor Day. Nissen's portion starts at the 1:45 mark and goes for ~30 minutes. Nissen very elegantly walks us through the history of the LDL-lowering clinical trials with statins and more recently Esperion's bempedoic acid (ETC-1002). Although statins and bempedoic acid lower LDL via inhibition of HMG-CoA reductase and ATP-citrate lyase, respectively, many statins and bempedoic acid also have anti-inflammatory effects as evidenced by their effects on hsCRP. Are the cardioprotective effects of these LDL-lowering drugs due solely to LDL-lowering or does the hsCRP lowering have a cardioprotective effect? Is the hsCRP lowering due to LDL lowering, or is hsCRP modulated independently of LDL? Nissen walks us through the data, including the recent CANTOS trial, that provides strong data to support that these drugs modulate hsCRP independent of their effects on LDL, and that both LDL lowering and anti-inflammatory effects independently and additively affect the overall cardioprotective profile.