UPDATED // The use of fish oil supplements to protect the cardiovascular system (CV) has been a controversial topic for years. Vascepa (Amarin), a prescription fish oil with high-dose ikosapent ethyl, recently received an expanded indication from the US Food and Drug Administration (FDA) to reduce the risk of CV in some patients with elevated triglyceride (TG) levels. Because not all fish oil products – prescription or dietary supplements – are created equal, there are five key pieces of information you should keep in mind about using them.

1. Icosapent Ethyl is the only prescription omega-3 fatty acid approved for CV reduction.

With its expanded indication, icosapent Ethyl can now be used as a supplement to statin therapy to reduce CV events in patients with elevated TG levels (≥ 150 mg / dl) and established atherosclerotic cardiovascular disease (ASCVD) or diabetes and at least two others CV reduce risk factors. This recommendation is based on results from REDUCE-IT, which showed a 25% reduced risk of serious CV events in patients with icosapent ethyl and a 35% reduced risk reduction in participants with a history of ASCVD.

This concentrated eicosapentaenoic acid (EPA) -prescription-only omega-3 polyunsaturated fatty acid (PUFA) was linked to a higher rate of atrial fibrillation and bleeding on REDUCE-IT, and while this is noted in the prescribing information under Warnings and Precautions by the FDA I thought not that these effects warrant a contraindication.

Previous studies with lower doses (1 g) of combined EPA / docosahexaenoic acid (DHA) pills showed no reduction in results in patients at risk without prior CVD, even in those with diabetes. The STRENGTH study with high-dose (4 g) omega-3 carboxylic acid / EPA in patients with a high risk of CV and elevated TG levels was recently terminated prematurely for reasons of futility.

Regardless of whether the TG lowering alone or additional pleiotropic anti-inflammatory, antithrombotic effects explain the extent of the CV risk reduction observed with REDUCE-IT is controversial.

2. While the prescription fish oils currently available are effective at lowering TG levels, there are differences between the products in terms of formulation and effectiveness.

The prescription fish oils available are not real fish oil products, but rather various formulations of omega-3 fatty acids derived from fish oil. There are currently five prescription omega-3 PUFAs available in the US, four of which are FDA approved for lowering serum TG levels (table) and one (Vascazen, Pivotal Therapeutics), an FDA-regulated medicinal food for omega is -3 deficiency in patients with CVD.

Table. Currently available, FDA-cleared omega-3 PUFA formulations

Brand name

formulation

EPA (g) per 1 g capsule

DHA (g) per 1 g capsule

Omega-3 dose (g) per 4 g

Epanova

Omega-3 carboxylic acids / DHA

0.55

0.2

3.0 EPA + DHA

Lovaza

Omega-3 acid ethyl ester / DHA

0.43

0.345

3.1 EPA / DHA

Back up again

Omega-3 acid ethyl ester / DHA

0.43 *

0.345 *

3.1 EPA / DHA

Vascepa

Icosapent ethyl

0.88

0

3.5 EPA

* Amount per 1.2 g capsule. Adapted from the AHA Science Advisory on omega-3 fatty acids.

While all prescription omega-3 PUFAs have similar TG-lowering effects, differences exist in their effects on high-density lipoprotein cholesterol (LDL-C) and lipoprotein cholesterol (HDL-C) levels. Studies have shown that the DHA-containing omega-3 PUFA increases LDL-C and can moderately increase HDL-C, while studies have shown that the EPA-pure omega-3 PUFA significantly increases serum TG levels lowers without increasing LDL-C in both patients and from statin therapy and decreases HDL-C slightly.

3. Prescription fish oils are not indicated for all patients with elevated TG levels.

With the exception of the medical food EPA / DHA formulation and the use of high-dose ikosapent ethyl to reduce CV events, the currently available prescription fish oils are approved by the FDA as a supplement to dietary intervention in adult patients with very high TG levels (≥ 500 mg / dl). The American Heart Association (AHA) Science Advisory on Omega-3 Fatty Acids for the Treatment of Hypertriglyceridemia states that “For all degrees of elevated triglyceride levels, treatment or elimination of secondary causes and extensive diet and lifestyle changes is recommended prior to direct pharmacotherapy “.

According to the FDA cleared indication, omega-3 PUFA products are intended for adult patients. Although prescription strength omega-3 PUFAs appear to be well tolerated in pediatric patients, studies to date have not shown significant effectiveness in lowering TG levels in this patient population.

Since the prescription omega-3 PUFAs come from fish sources, they should be used with caution in patients with known hypersensitivity to fish or shellfish.

Caution should also be exercised when prescribing omega-3 PUFA to patients with hepatic impairment. Monitoring alanine aminotransferase and aspartate aminotransferase levels is recommended as some formulations of EPA / DHA can increase serum levels of these enzymes.

4. Sea-based dietary supplements are not a substitute for prescription omega-3 PUFA to lower TG levels.

While they can play a complementary role in diet, marine oil-based omega-3 fatty acid supplements such as fish oil, calanus oil, and krill oil are neither recommended nor indicated as a substitute for prescription omega-3 PUFA for lowering serum TG levels or treating disease .

The FDA-cleared prescription omega-3 PUFA contains pharmaceutical doses of highly purified, regulated concentrations of DHA / EPA in combination or EPA alone. Marine oil supplements contain sub-therapeutic amounts of omega fatty acids (including products that are said to be double or triple strength). Because these products are not tested, approved, or monitored by the FDA, there is no guarantee of their quality. Potency and Security.

In addition, marine oil supplements contain a variety of other non-therapeutic ingredients – in some cases cholesterol, oxidized fatty acids, or contaminants. Patients taking these products also risk exposure to higher amounts of oxidative products, and some of these supplements have been found to contain high amounts of saturated fats that interfere with the supposed beneficial effects of these products. Omega-3 PUFA supplements that have been voluntarily tested to independently confirm their contents have the US Pharmacopeial Convention symbol on the label.

With more than 100 marine oil-based dietary supplements available and marketed for consumers, an expert analysis by the American College of Cardiology found the temptation of some patients to switch from more expensive prescription PUFA to a lower-cost dietary supplement. To facilitate compliance with the prescribed marine oil and discourage patients from switching to a supplement, the authors of this analysis recommend that clinicians provide information about the coverage support available.

5. Prescription Omega-3 PUFA can prove cost effective by reducing the clinical and economic burden.

In terms of cost, the average retail price for a 30-day supply of Lovaza (4g EPA / DHA) is $ 202.39 and a 30-day capsule supply of Vascepa is around $ 348-364 (or about $ 245 with Manufacturer coupon)). These costs can be offset by some private insurance plans, Medicare and Medicaid.

The clinical burden of severe hypertriglyceridemia is associated with significant health care costs. In the US, the annual economic burden associated with high TG is estimated at $ 10.7 billion. Previous studies suggest that the cost of prescription omega-3 PUFAs could be offset by the positive effects such as reduced morbidity and mortality of CV, as well as a lower risk of pancreatitis, kidney disease, and diabetes-related events in those with very high triglycerides.

More recently, results from non-profit analysis have confirmed the cost-effectiveness of icosapent ethyl as an adjunct to statin therapy. An analysis of the data from REDUCE-IT found that icosapent Ethyl had “better results with lower healthcare costs” ($ 4.16 / day for eligible patients), making it not only inexpensive but also cost effective when compared to placebo.

Tracey L. Giannouris, MA is a freelance medical / clinical writer based in Flemington, New Jersey. She has worked on various peer-reviewed and ongoing publications related to medical education in human and animal health care for nearly two decades.

Editor’s Note: This article has been updated with information about the STRENGTH Trial and how to fix some bugs. An earlier version incorrectly referred to over-the-counter marine oil supplements, but these products are dietary supplements, not over-the-counter drugs. Shellfish allergy is a caution and not a contraindication to the use of prescription omega-3 PUFA products.

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