STRENGTH Trial Disheartening for Fish Oil Craze

Researchers reported at the virtual scientific sessions of the American Heart Association that omega-3 fatty acids, formulated with carboxylic acid for greater bioavailability, made no difference in cardiovascular event rates in the STRENGTH trial, which was stopped early for futility.

In this exclusive MedPage Today video, the Cleveland Clinic's Steven Nissen, MD, chair of STRENGTH's executive committee, explains the difference between the negative findings in STRENGTH and the positive findings in the REDUCE-IT trial with a different omega-3 product, and the huge clinical implications.

Following is a transcript of his remarks:

Many clinical trials have tested the effect of fish oil on cardiovascular outcomes and virtually all of them have been negative, with one exception, the REDUCE-IT trial, which used a purified form of EPA.

We conducted in parallel the STRENGTH trial, which uses a carboxylic acid derivative of omega 3 that gets very high blood levels of omega 3 fatty acids, including EPA, but a little bit of DHA. The STRENGTH trial showed absolutely no effect of high doses of fish oil on cardiovascular outcomes. There was no benefit for the primary or the secondary endpoints. It was essentially stunningly neutral, with a hazard ratio of 0.99, and the question is, "Why?"

It turns out that when we were designing STRENGTH we knew that we needed to have a placebo that would appear identical, but that would have no effects, and after much discussion we used corn oil. What you'll see is that the corn oil group, there was no effect on any of the lipid or inflammatory biomarkers.

If you then compare STRENGTH and REDUCE-IT, you see an absolutely stunning finding. In REDUCE-IT, C-reactive protein in the control group, which used mineral oil, went up over 30%. LDL went up. apoB went up. We think that STRENGTH demonstrates fairly clearly that REDUCE-IT is a false positive study, that what you really are seeing is the adverse effects of mineral oil and not the favorable effects of purified EPA.

Now, obviously, this has huge clinical implications. The drug used in the REDUCE-IT trial, which is a purified form of EPA being very widely promoted, it's being advertised on television, we think it's a false positive result. We think STRENGTH was done very well. We had almost 1,600 endpoints and it is completely neutral when compared to a neutral control, in this case, corn oil.

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