LOVAZA: Limited Use Drug for Lowering Trigylcerides

Since 2003, drug manufacturer GlaxoSmithKline has been promoting omega-3-acid ethyl esters (LOVAZA), a specific formulation of purified fish oil that contains two types of omega-3 acids in each 1g capsule, as an adjunct to diet to reduce very high (greater than 500 mg/dL) triglyceride levels in adult patients. In its analysis of the available evidence, Worst Pills, Best Pills News has classified this drug as Limited Use, meaning this drug offers limited benefit and patients should first try altering their diet to consume the amount of omega-3 acids found to reduce heart disease.

Several clinical trials have supported the fact that people who consume lower amounts (1 to 2 g/day) of omega-3 acids (a type of unsaturated fatty acid found in high concentration in fish oil shown to reduce levels of triglycerides, a type of fat) are less likely to die from ischemic heart disease.

High levels of triglycerides have been associated with increased cardiovascular disease and death. People with very high levels of triglycerides (greater than 500 mg/dL) are also at risk for pancreatitis, an inflammation of the pancreas that is usually associated with abdominal pain and can be life-threatening in some cases.

Side effects and clinical trials

LOVAZA has not been associated with any serious side effects. The most common adverse events are belching and a fishy taste, both present in less than 5 percent of people who took the drug at a dose of 4g/day in clinical trials.

LOVAZA was approved by the Food and Drug Administration (FDA) at a dose of 4g/day to reduce very high triglyceride levels, but not moderate elevations (elevated but less than 500 mg/dL), because of the possible cardiovascular risks associated with the increase in LDL cholesterol. Also, the FDA has not allowed the marketing claim that LOVAZA prevents cardiovascular disease or pancreatitis because, although LOVAZA lowers triglycerides, these clinical outcomes have not been studied in clinical trials with this drug.

Because of the evidence that omega-3-acids, either from dietary intake or lower-dose dietary supplements (1-2g/day), can help reduce the risk of cardiovascular disease, the FDA has issued a Qualified Health Claim for these lower-dose supplements, stating that "supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease."

The FDA was also careful to state that "dietary supplements should not recommend or suggest in their labeling a daily intake exceeding 2 grams of EPA and DHA," which is less than the amount of omega-3 acids in the FDA approved dose of LOVAZA. A Qualified Health Claim characterizes a relationship between a non-drug substance and a disease or health-related condition that is supported by scientific evidence, which is reviewed by the FDA through a petition process.

In a small randomized placebo-controlled trial of patients with very high triglyceride levels, LOVAZA at a dose of 4g/day reduced triglyceride levels by half. However, LDL ("bad" cholesterol) levels were increased by a similar amount and clinical outcomes were not measured. Elevated levels of LDL cholesterol are associated with a greater risk of heart disease, but it is unclear if the elevation in LDL levels seen with high-dose LOVAZA therapy is harmful.

Other small randomized placebo-controlled trials have been conducted in patients with triglyceride levels that are high but less than 500 mg/dL, showing a similar reduction in triglycerides and increase in LDL cholesterol.

Further studies are required to determine if the high dose of omega-3 acids in the FDA-approved dose of LOVAZA (4g/day) alters the risk of heart disease and cardiovascular mortality.

What You Can Do

If you are at risk for or already have cardiovascular disease, your physician may recommend that you increase your dietary intake of oily fish or take a low-dose supplement (less than 2 g/day) of omega-3-acids. The amount of omega-3 acids contained in oily fish varies by type.

If you have very high levels of triglycerides (greater than 500mg/dL), your physician may recommend LOVAZA to lower your triglyceride, level, because of the association between very high levels of triglycerides and pancreatitis.

Patients taking LOVAZA should have periodic liver function and cholesterol tests, including triglyceride and LDL levels.