Vascepa™, an Omega-3 Fatty Acid, for Patients with Severe Hypertriglyceridemia

Cincinnati—Approximately 4 million people in the United States have severe hypertriglyceridemia, which has been associated with heart disease, stroke, and other conditions. The effects are intensified in people with low high-density lipoprotein cholesterol (HDL-C) and elevated levels of low-density lipoprotein cholesterol (LDL-C).

In July, the FDA approved Vascepa^™ (icosapent ethyl) as an adjunct to diet to reduce triglyceride levels in patients with severe hypertriglyceridemia, which is defined as trigylcerides ≥500 mg/dL.

Icosapent ethyl was discussed at the AMCP meeting in a product theater sponsored by Amarin Corporation, the manufacturer of the drug. As of October 2012, the FDA had not determined the status of Amarin’s request for 5-year, new chemical entity exclusivity for icosapent ethyl.

The speakers noted that no event studies determined if icosapent ethyl decreased cardiovascular mortality and morbidity. In addition, the drug was approved before a large group trial had been conducted to assess clinical efficacy in reducing disease.

Causes of severe hypertriglyceridemia include diabetes, obesity, genetic disorders, and lifestyle factors. Treatment guidelines recommend targeting trigylcerides for the prevention of acute pancreatitis.

Omega-3 and omega-6 are 2 types of essential fatty acids. In the United States, most diets are low in omega-3 fatty acids.

Icosapent ethyl contains ethyl esters of eicosapentaenoic acid, an omega-3 fatty acid. The recommended dose is 4 grams per day taken as 2 capsules twice daily with food.

The drug’s safety and efficacy was determined in a randomized, placebo-controlled, double-blind, parallel group study that enrolled patients with baseline triglyceride levels between 500 and 2000 mg/dL. They took icosapent ethyl (n=76) or placebo (n=75) for 12 weeks. At baseline, the median triglyceride level was 684 mg/dL, the median LDL-C was 86 mg/dL, and the median HDL-C was 27 mg/dL. The mean age was 53 years, while 88% of patients were Caucasian and 76% were male.

The study found that patients who took 4 grams per day of icosapent ethyl had a reduction in median triglyceride level, very-low-density lipoprotein cholesterol, and apolipoprotein B compared with the placebo group. The authors noted that the reduction in triglyceride level in the icosapent ethyl group was not associated with elevated LDL-C.

In a pooled analysis of 2 trials, arthralgia was the only adverse reaction, occurring in >2% of patients taking icosapent ethyl and at a higher rate than for placebo patients.

Before taking icosapent ethyl, patients should be placed on a lipid-lowering diet and exercise regimen. When they begin treatment, they should continue with the same diet and exercise regimen to control medical problems that could lead to lipid abnormalities, including diabetes, hypothyroidism, and alcohol intake. They are also advised to stop taking beta blockers, thiazides, estrogens, and other medications that exacerbate hypertriglyceridemia.

Patients who have hepatic impairment should have their alanine aminotransferase and aspartate aminotransferase levels monitored when taking icosapent ethyl. Patients should also be cautious if they are hypersensitive to fish and/or shellfish, although it is unknown if they are at an increased risk of allergic reactions to icosapent ethyl.

In addition, patients treated with icosapent ethyl and other drugs affecting coagulation should be monitored periodically because studies have shown omega-3 fatty acids prolong bleeding time. However, in this study, the prolonged bleeding time did not exceed normal limits and did not lead to clinically significant bleeding episodes.