The first question is whether icosapent ethyl has anti-inflammatory effects. To my knowledge, the ANCHOR and MARINE studies were the first to suggest anti-inflammatory effects of icosapent ethyl, both of which used mineral oil as a placebo. If mineral oil has proinflammatory effects, then the biomaker results in the ANCHOR and MARINE studies may have been enhanced by the action of mineral oil, raising the question of the anti-inflammatory effects of icosapent ethyl. However, considering the results of the CardioLink-9 trial, some anti-inflammatory effect may be possible. If mineral oil has no proinflammatory effect, it is possible that the REDUCE-IT sample group had elevated inflammatory markers as a natural consequence of their age and comorbidities. The possibility that icosapent ethyl prevented that natural rise cannot be ruled out. In fact, the answer may lie somewhere in between. In other words, icosapent ethyl may have an anti-inflammatory effect, but mineral oil may have a more or less proinflammatory effect.
My personal opinion is that CVOT is what the medical industry cares most about, not anti-inflammatory or cardiovascular risk markers. If these markers were sufficient, the REDUCE-IT trial would not have been necessary and the ANCHOR trial would have been sufficient. We know how much LDL levels increase the risk of cardiovascular disease (about 3% according to the FDA?) but we may not know to what extent elevated levels of other markers are involved in the increased risk of cardiovascular disease.
The results of this study may make people more hesitant to prescribe icosapent ethyl, but I suspect that the impact will not be as strong.
The results of RESPECT-EPA are eagerly awaited, but it is a double-edged sword.
