Omega-3-acid ethyl esters is used as an adjunct to dietary therapy to reduce triglyceride concentrations in adults with severe hypertriglyceridemia (triglyceride concentration of 500 mg/dL or greater). Efficacy of the drug in reducing the risk of pancreatitis or the risk of cardiovascular morbidity or mortality in patients with very high triglyceride concentrations has not been established.
The Third Report of the National Cholesterol Education Program (NCEP) (Adult Treatment Panel [ATP] III) stated that the initial treatments of choice are nondrug therapies and measures (lifestyle modifications) specific for the type of dyslipidemia specific for the type of dyslipidemia, including dietary management (e.g., restriction of saturated fat and cholesterol intake, addition of plant stanol/sterols and viscous fiber to diet), weight control, an appropriate program of physical activity, and management of potentially contributory disease.
(See Adjunctive Measures under Warnings/Precautions: General Precautions, in Cautions.)Drug therapy is not a substitute for but an adjunct to these nondrug therapies and measures, which should be continued when drug therapy is initiated.
Safety and efficacy of omega-3-acid ethyl esters in the management of hypertriglyceridemia have been established in several randomized controlled studies. In 2 randomized, double-blind, placebo-controlled studies of 6 or 16 weeks' duration, 84 patients with very high triglyceride concentrations (median baseline triglyceride concentration of 792 mg/dL) were randomized to receive either omega-3-acid ethyl esters (4 g daily as Lovaza capsules) or placebo. In these studies, patients who received omega-3-acid ethyl esters had reductions of approximately 45% in triglyceride concentrations, 42% in very low-density lipoprotein (VLDL)-cholesterol concentrations, and 14% in non-high-density lipoprotein (non-HDL)-cholesterol (total cholesterol minus HDL-cholesterol) concentrations; increases of approximately 9% in HDL-cholesterol concentrations also were reported.
In a double-blind, placebo- and active-controlled study, 254 patients with severe hypertriglyceridemia (median baseline triglyceride concentration of 675 mg/dL) were randomized to receive 4.8 g of omega-3-acid ethyl esters (as Omtryg capsules) daily, 4 capsules daily of another omega-3-acid ethyl esters preparation (each capsule contains at least 900 mg of ethyl esters from omega-3 fatty acids from fish oils), or placebo for 12 weeks. In this study, patients treated with omega-3-acid ethyl esters (Omtryg) had reductions of approximately 25% in triglyceride concentrations, 21% in VLDL-cholesterol concentrations, and 9% in non-HDL-cholesterol concentrations; no changes in HDL-cholesterol concentrations were reported. Patients treated with 4 capsules daily of the other omega-3-acid ethyl esters preparation had reductions of approximately 27% in triglyceride concentrations, 18% in VLDL-cholesterol concentrations, and 4% in non-HDL-cholesterol concentrations; no changes in HDL-cholesterol concentrations were reported.
Treatment with omega-3-acid ethyl esters may result in increases in low-density lipoprotein (LDL)-cholesterol and non-HDL-cholesterol concentrations in some individuals. In clinical studies with omega-3-acid ethyl esters, median baseline LDL-cholesterol concentrations (89 mg/dL) were increased by approximately 45% following therapy with omega-3-acid ethyl esters. Therefore, patients receiving omega-3-acid ethyl esters should be monitored periodically to ensure that LDL-cholesterol concentrations do not increase excessively.
Omega-3-acid ethyl esters has been used to reduce high (200-499 mg/dL) triglyceride concentrations in adults. However, because target LDL-cholesterol goal has been determined by ATP III to be the primary treatment objective in this patient population, most patients are expected to receive hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) as initial therapy. Thus, although monotherapy with omega-3-acid ethyl esters has been shown to reduce triglyceride concentrations by approximately 28% in patients with high triglyceride concentrations, some experts state that efficacy of the drug in this patient population should be further evaluated in patients receiving concomitant statin therapy. Studies evaluating effects of omega-3-acid ethyl esters on triglyceride, LDL-cholesterol, and non-HDL-cholesterol concentrations in patients receiving concomitant statin therapy are ongoing. Meanwhile, limited data from several small studies in patients with hypertriglyceridemia indicate that addition of omega-3-acid ethyl esters (4 g daily) to existing atorvastatin (40 mg daily) or simvastatin (10-40 mg daily) therapy for at least 5 weeks further reduced triglyceride or VLDL-cholesterol concentrations by an additional 14-30 or 25-40%, respectively.
Prevention of Cardiovascular Events
Marine- and plant-derived omega-3 fatty acids (i.e., EPA, DHA, α-linolenic acid) have been evaluated for use for primary or secondary prevention of coronary heart disease (CHD). Data from epidemiologic as well as prospective, randomized, controlled studies suggest that higher intakes of dietary or supplemental omega-3 fatty acids reduce the risk of cardiovascular events or CHD mortality; however, conflicting data exist.
The American College of Cardiology (ACC)/American Heart Association (AHA) guideline for management of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults states that nondrug therapies (i.e., lifestyle modifications), which include adherence to a heart-healthy diet, regular exercise, avoidance of tobacco products, and maintenance of a healthy weight, are the foundation of atherosclerotic cardiovascular disease (ASCVD) prevention. The guideline also states that nonstatin therapies (e.g., omega-3-acid ethyl esters) do not provide acceptable ASCVD risk reduction benefits compared to their potential for adverse effects in the routine prevention of ASCVD. However, nonstatin drugs may be useful as adjuncts to statin therapy in high-risk patients (e.g., patients with ASCVD, patients with LDL-cholesterol concentrations of 190 mg/dL or higher, patients with diabetes mellitus) who have a less-than-anticipated response to statins, are unable to tolerate even a less-than-recommended intensity of a statin, or are completely intolerant to statin therapy. When a nonstatin drug is required, selection of the nonstatin drug should be based on a favorable benefit-risk ratio (i.e., demonstrated benefit of ASCVD risk reduction outweighs risks of adverse effects and drug interactions) and patient preferences. For additional details on prevention of ASCVD, and also consult the most recent ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (available at http://www.cardiosource.org or http://my.americanheart.org).
(See Prevention of Cardiovascular Events under Dosage and Administration: Dosage.)