“I think for now, we have to accept the REDUCE-IT results as a positive finding. However, the STRENGTH trial did amplify these questions a bit since there was no signal at all for benefit, and this heightens the call for additional trials of high-dose EPA formulations, including icosapent ethyl, versus corn oil or another neutral comparator,” he said.
Discussant of the STRENGTH trial at the AHA late-breaker session, Alberico Catapano, MD, PhD, University of Milan, noted that DHA may have less biological activity than EPA.
“We don’t know for certain, but there are studies suggesting that EPA may have more effect on stabilizing plaque membranes,” Dr. Catapano said. “Certainly, the dose of EPA was different in the two studies, and in my view this could be part of the explanation. But we are still in place where we need more evidence.”
In an editorial accompanying the JAMA publication of STRENGTH, Garima Sharma, MD, Seth S. Martin, MD, and Roger S. Blumenthal, MD, Johns Hopkins University, Baltimore, said the trial’s findings “may invigorate further investigation regarding IPE [icosapent ethyl], generate additional constructive debate around the optimal placebo control, and should prompt reconsideration of over-the-counter mixed omega-3 fatty acid products for ASCVD [atherosclerotic cardiovascular disease] prevention.
“This latter point is especially important given the lack of evidence for benefit, and the potential for harm due to increased AF [atrial fibrillation],” they noted.
“The reasons the findings from the REDUCE-IT trial were positive and the STRENGTH trial were not, and that EPA levels correlated with outcomes in REDUCE-IT but did not in STRENGTH, remain uncertain,” they concluded. “The importance of the specific omega-3 formulation in achieving ASCVD risk reduction and the degree to which the placebo (i.e., mineral oil vs corn oil) may have affected outcomes remain unresolved.”
The STRENGTH trial was sponsored by AstraZeneca. Dr. Lincoff reported receiving grants from AstraZeneca during the conduct of the study. Dr. Catapano has received honoraria, lecture fees, or research grants from Sigma-Tau, Manarini, Kowa Pharmaceuticals, Recordati, Eli Lilly, AstraZeneca, Mediolanum, Pfizer, Merck, Sanofi, Aegerion, Amgen, Genzyme, Bayer, Sanofi, Regeneron Daiichi Sankyo, and Amarin. Dr. Martin reports receiving consulting fees from AstraZeneca, Amgen, Esperion, and REGENXBIO, and has a patent pending for a system of LDL-C estimation filed by Johns Hopkins University. Dr. Bhatt reports serving as principal investigator for REDUCE-IT and that Brigham and Women’s Hospital has received research funding from Amarin.
A version of this article originally appeared on Medscape.com.