CVD Benefits in Fish Oil: Is EPA the Pearl?

Carol Peckham; Howard S. Weintraub, MD


June 05, 2013

In This Article

Looking at EPA

Medscape: So, is fish oil then also out of the question for cardiovascular protection?

Dr. Weintraub: If you were to put 50 cardiologists and endocrinologists in the same room and ask them to name 1 study in which another medicine was added to a statin and there were meaningful significant reductions in cardiovascular events, they would probably look around and not be sure. I would say that one such study is JELIS,[11,12,13] which was conducted in Japan and added fish oil to a statin for patients with high cholesterol (6.5 mmol/L or greater). It's important to note that the study used only EPA, with a purity of something like 94% or 96%. At a mean follow-up of 4.6 years, they observed a 19% relative reduction in major coronary events in those on EPA, although the effect on triglycerides in that trial was not dramatic. Unstable angina and nonfatal coronary events were significantly reduced. Sudden cardiac death and coronary death did not differ between groups. Granted, nobody on our side of the pond thinks that trials populated exclusively with Asian participants would necessarily indicate the same results in people in Europe or the United States, but I think it's an interesting phenomenon.

A small US company has made its own version of EPA, icosapent ethyl (Vascepa®; Amarin Pharma), which has been approved. They conducted 2 studies: ANCHOR[14] and MARINE,[15] which allowed the FDA to approve icosapent ethyl for the same indication as the other approved fish oil (Lovaza®; GlaxoSmithKline), a combination of EPA and DHA, with a ratio of about 4:3.

The MARINE study looked at people with triglyceride levels over 500 mg/dL, which represents about 1% to 2% of the US population, and the ANCHOR study looked at those with triglyceride levels between 200 and 500 mg/dL, which reflects a larger proportion -- about 20% -- of the US population. One interesting observation was that using a statin along with EPA achieved much greater triglyceride reductions than using EPA without a statin, and the stronger the statin, the better the effect. So, the interaction between EPA and statins is intriguing. Fish oils may not be dead in the water for this reason alone.

The good news is that we're going to have to wait only 2 to 4 years for answers to the question of whether EPA is beneficial in high-risk patients. An event trial with at least 50% currently recruited is looking at the concomitant addition of icosapent ethyl to therapy in individuals with documented cardiovascular disease and/or diabetes.

I certainly haven't seen any studies in major journals on any comparative difference between the DHA/EPA combinations and the EPA-only agents. However, if you look at the FDA's Pharmaceutical Inspectorate (PI) for Lovaza, and in most of the data that the company has compiled, there is an average net increase in LDL cholesterol. Obviously this can turn some people off. We almost get the same kind of information that was out there with rosiglitazone, when, if you remember, LDL was increased in many of its studies. So, whether this mattered or not, certainly LDL is one of the few things in the lipid world that we have relative agreement on, that it is bad for you. There are some very interesting theories floating around, but I think that being LDL neutral and reducing inflammatory markers and triglycerides, as is indicated in the MARINE and ANCHOR studies on EPA, may be the difference in how these fish oil drugs behave.


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