"..... how an Apabetalone success might affect AMRN and Vascepa. Are they competitive or complementary? My opinion, fwiw, is that right now it's very hard to tell. Vascepa may have benefits far beyond the indications for which it has been tested."

Both! I can see Vascepa and Apabetalone being used together down the road. But I'm sure some physicians will prescribe/advise to use an either/or approach. This is not unique to Vascepa. Recent CVOTs have shown cardiovascular benefit with SGLT2 inhibitors and GLP-1R agonists in diabetics. There are some diabetics on both SGLT2 inhibs and GLP-1R agonists. I'm sure there are some patients on Vascepa in addition to SGLT2 inhibs and/or GLP-1R agonists. Bromodomain-2 selective BET inhibition via apabetalone affects a lot of different biological pathways. Omega-3 fatty acids (i.e. EPA ethyl esters; Vascepa) also affect a lot of different biological pathways. Surely, some of these affected pathways overlap between apabetalone and Vascepa. However, there are likely going to be more differences than similarities. There is no one size fits all approach. Patients have different needs/tolerances and doctors have different prescribing preferences. The more tools in the toolbox, the more potential combinations and/or decision making.

"The EVAPORATE trial - later this year - will be a start on clarifying that, for better or for worse."

Please expand on how the EVAPORATE trial will clarify the above. Are you simply suggesting that showing plaque reduction in EVAPORATE will clarify one of the ways that Vascepa is cardioprotective?

"Also, there is a "school" of thought that Vascepa does not work by lowering triglycerides, but that lowered triglycerides are a biomarker for lower systemic inflammation (SI), i.e. that Vascepa works directly on SI and not indirectly via lowering triglycerides."

Correct. MACE reduction in REDUCE-IT was more or less indepedent of triglyceride reduction, baseline triglyceride level and achieved triglyeride level. So REDUCE-IT wasn't so much a trial that proved plasma triglyerides to be a cardio risk factor, but more a trial to prove the omega-3 fatty acid hypothesis via 4g/day Vascepa (EPA ethyl esters). It was already well known that omega-3 fatty acids have effects on many facets of biology/physiology including inflammation. Plasma triglycerides reside primarily in triglyceride-rich apolipoprotein-B containing lipoproteins. Mainly very-low density lipoproteins, which are the precursors to LDL. Lipoprotein assembly/secretion from the liver and lipoprotein turnover/catabolism in the circulation are very complex processes with many contributors. It is an extreme oversimplification to state the plasma TG are a biomarker for inflammation. Omega-3 fatty acids can reduce plasma TG and reduce inflammation, but that does not mean that the two are related or dependent on one another.

BearDownAZ