This is an interesting definition of marginal significance, with P=0.12 (more than double the standard 0.05) and 10%+ OR overlap. You seem to be focusing on OR

This is an interesting definition of marginal significance, with P=0.12 (more than double the standard 0.05) and 10%+ OR overlap. You seem to be focusing on OR means too much. Absolute risk adjustments are surprisingly low considering certain predictions. I agree with the conclusion that 106 mg/dL mean could've reduced the power of the experiment. I also agree that a good followup is relevant and important. It could change results a lot, including the initial positive results. However, in the meantime, we have no way to actually evaluate the risks and are essentially making educated guesses. Note that the patients treated were on average 60 years old. This reduces followup time considerably but also reduces potential effect size. The results are mostly based on ODYSSEY LONG TERM and FOURIER trials. The former verified PCSK9i alongside high dose statin therapy. The latter used a monotherapy in some cases but not defined the subgroup. FOURIER alone is quite damning. ODYSSEY LONG TERM does not consider mortality endpoints. Such interesting tidbits like "In terms of individual outcomes, evolocumab had no observed effect on cardiovascular mortality, and hence P values for other outcomes should be considered exploratory." The inhibitors in question were allegedly not mainly tested here as an adjunct to statin therapy or replacement for resistant cases, but it so happened anyway. You're supposed to be comparing it to current best known treatment which is statins, which is a very valid comparison. Any other comparison would only be of educational value but should be done regardless. It is even more suspect that it was not done but instead it was used as an adjunct. Not even canadian cross design was used...