A new analysis of the REDUCE-IT study has reignited concerns that the benefit shown by the high-dose fish oil product in the study, icosapent ethyl, may have been related to harms caused by the placebo mineral oil.
The authors, led by Paul Ridker, MD, Brigham & Women's Hospital, Boston, do not voice much opinion on what the results mean, concluding that"the effect of these findings on the interpretation of theThey also say that a second icosapent ethyl trial using a nonmineral oil comparator"would help resolve ongoing controversy."
Lead investigator of the REDUCE-IT trial, Deepak Bhatt, MD, also from Brigham & Women's Hospital, who is the senior author of the current study, played down the new findings, saying they did not offer much new incremental information on mechanistic insight. "The result of this new analysis shows that mineral oil increases virtually every inflammatory and lipid marker that they measured," he commented to."There are a lot of theories, but the bottom line is that something really bad happened in the mineral-oil group which makes icosapent ethyl look efficacious. In my view, this needs to be reviewed by the FDA for consideration of removing the label claim for cardiovascular benefit.
"My point is...once you know you have non-neutral comparator and the effect on risk biomarkers is far from trivial…then you have introduced substantial uncertainty about the trial result, as conveyed by the authors…and no one can say what would happen with a neutral comparator," Krumholz writes.