To reap benefits of fish oil, formulation and dose might matter

If you’ve been hearing a lot about fish oil, it’s not your imagination. Late last year, results from two major trials—REDUCE-IT (Reduction of Cardiovascular Events With EPA – Intervention Trial) and VITAL (Vitamin D and Omega-3 Trial)—were released, clueing patients and health care providers into the benefits fish oil can have, if any. At best, results from these new trials provide some information on how formulation and dose of fish oil could make a difference.

Deepak L. Bhatt and colleagues performed a randomized controlled trial REDUCE-ITwith patients taking icosapent ethyl (Vascepa—Amarin), a substance derived from a component of fish oil approved by FDA in 2012 to treat patients with high triglyceride levels.

The REDUCE-IT results, published November 10, 2018, in the New England Journal of Medicine, showed that icosapent ethyl, a prescription drug containing highly purified eicosapentaenoic acid (EPA), lowered the risk of cardiovascular events by 26% for patients who either had cardiovascular disease (CVD) or were at high risk for developing it and were on a moderate- to high-intensity statin.

The majority of patients in the study had CVD and an LDL-C level of 41 mg to 100 mg per dL while on statin therapy, but also had a fasting triglyceride level of 135 mg to 499 mg per dL.

“For patients who fit these criteria, I’m encouraged that we have another drug in the armamentarium of medications that can potentially slow the progression of cardiovascular disease and lower the risk of recurrent cardiovascular events,” said Zachary Noel, PharmD, BCPS, an assistant professor at the University of Maryland School of Pharmacy.

Noel said he is skeptical about applying the results to patients who do not have established CVD but are at risk of developing it. Only 30% of patients in the trial received the medication for primary prevention.

“Icosapent ethyl is a reasonable option for secondary prevention of cardiovascular events for select patients already taking a statin who still have elevated triglycerides, but at this point in time it has a limited role in primary prevention and should only be considered in certain high-risk patients,” said Noel.

Results as good as those seen in REDUCE-IT also raise doubts, however. Skepticism has stemmed mainly from the belief that use of mineral oil capsules as the placebo could have potentially harmed patients and skewed results in favor of icosapent ethyl. But a review of the literature doesn’t back up any negative claims about mineral oil.

Mark Cziraky, PharmD, CLS, vice president of research at HealthCore, said that while this was a well-conducted trial, he would like to have more information on the effect of icosapent ethyl in the context of other evidence-based prevention therapies and additional independent risk factor management in the high-risk population studied. In addition, because the minority of patients in this study were on high-intensity statin therapy at the start of the study, the question remains as to whether intensifying statin therapy to gain additional LDL-C lowering would yield similar or even greater results, as seen with the addition of icosapent ethyl in this trial.  

Amarin, the maker of icosapent ethyl, funded the REDUCE-IT research. The drug has the potential to be a blockbuster if trial results hold up.

Results from VITAL, published in two New England Journal of Medicine articles on November 10, 2018 (one article focused on vitamin D supplementation and the other on fish oil), showed that neither fish oil nor vitamin D prevented CVD.

Whereas REDUCE-IT used a pure EPA formulation at a daily dose of 4 g, VITAL used a 1-g fish oil product that contained EPA and docosahexaenoic acid (DHA) at doses of 460 mg and 380 mg, respectively.

“These two products vary drastically in both formulation and dose,” said Noel. “We don’t know what the best dose and ratio of EPA to DHA is, so it’s important to stick with products that have a proven benefit.”

In general, OTC fish oil products are made up of a much lower dose than prescription products and contain varying degrees of EPA and DHA.

The other main difference is that VITAL, which involved almost 26,000 healthy adults aged 50 and older, was a primary prevention trial. REDUCE-IT was not.

“It doesn’t appear that these patients benefit as much as those with established cardiovascular disease,” said Noel.

For the full article, please visit www.pharmacytoday.org for the February 2019 issue of Pharmacy Today.