Label could potentially be a sticky issue, especially primary prevention, because R-IT did not meet stat sig for PP - close, but no cigar. Here's what they asked for on ANCHOR label, and I can't see them asking for less for R-IT label:
“as an adjunct to diet and in combination with a statin to reduce TG, non-HDL-C, Apo B, LDL-C, TC, and VLDL-C in adult patients with mixed dyslipidemia and CHD or a CHD risk equivalent.”
Interesting, the ADA did make V SOC for that label:
Section 10 was updated based on the outcome of Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT), which determined the addition of icosapent ethyl to statin therapy for patients with high triglyceride levels reduced cardiovascular events. The Standards of Care now include a recommendation that icosapent ethyl be considered for patients with diabetes and atherosclerotic cardiovascular disease (ASCVD) or other cardiac risk factors on a statin with controlled LDL-C, but with elevated triglycerides (135-499) to reduce cardiovascular risk.
Per will "on a statin" be on label vs. what will happen in the real world, I'm 99% certain label will mention statin therapy but docs won't deny non-statin patients V if they have other risk factors or established CVD. One interesting factoid (but not so hot for those of us on V but not a statin) is that the low statin density V group saw no benefit, although it didn't meet stat sig (p = 0.10) and the 95% CI was wide as a truck:
IMO label asked for was TGs 135-499 despite the data showing no direct correlation between TGs and event rates - not having TGs mentioned at all given no known MOA would be too broad of a label for FDA to accept.
Lastly, I'd like to note that several of your questions are directly related to how doctors (endos) should practice medicine - that's not what the FDA is authorized to do, although they do on occasion try to do that - doesn't make it right.