Perspectives in the Management of Hypertriglyceridemia

In a session at the Fall Managed Care Forum 2015, held in Las Vegas, Nevada, cardiology expert Harold Bays MD, FTOS, FACC, FACE, FNLA, medical director and president of the Louisville Metabolic and Atherosclerosis Research Center, discussed treatments for hypertriglyceridemia. In his talk, Dr Bays emphasized the importance of greater adherence to evidence-based practice guidelines, and the relevance of treatment with omega-3 fatty acids.

According to Dr Bays, a fundamental of treatment for hypertriglyceridemia is the variation in the percentage reduction in triglyceride levels based on a patient’s baseline triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total cholesterol levels.

In a clinical trial of patients with baseline average triglyceride levels of 191 mg/dL, treatment with fenofibrate reduced triglyceride levels 29%, whereas patients with a baseline triglyceride level of 449 mg/dL experienced a 46% reduction in triglyceride levels following fenofibrate therapy. Continuing this trend, patients with an average baseline triglyceride level of 710 mg/dL experienced a 55% reduction in this metric with fenofibrate treatment.

Epidemiologic studies show an overall positive effect of omega-3 fatty acid supplementation and fish, or fish oil consumption in patients with cardiovascular disease. Although some studies did not identify any effect of omega-3 fatty acid consumption on cardiovascular parameters, such as, the1995 health professionals study, involving a total of 44,895 men, and the 12,763-man, 7-country study published in 1996, other epidemiologic studies show some evidence of a benefit, including the 75,725-participant Copenhagen Heart Study, and a 262,525-patient meta analysis of 29 studies published in 2007. Overall, these studies point to a net benefit of omega-3 fatty acid supplementation.

Potential cardiovascular benefits of omega-3 fatty acid consumption include a lower risk of developing arrhythmias, and thrombosis, as well as decreased platelet aggregation, a reduced risk of sudden death, improved blood rheologic flow, and a possibly lowered risk of developing atrial fibrillation. Omega-3 fatty acids may also reduce heart rate variability, reduce endothelial adhesion, increase expression of antiatherogenic adhesion receptors, reduce HDL-C levels, reduce levels of proinflammatory eicosanoids and leukotrienes, reduce triglyceride and very low density cholesterol (VLDL-C) levels, reduce chylomicron expression, decrease systolic and diastolic blood pressure, and increase HDL-C levels. Other evidence supports a role of omega-3 fatty acids in stabilizing atherogenic plaques.

In a study of more than 18,000 Japanese patients receiving statins, after 5 years of follow-up, patients receiving EPA at a daily dose of 1800 mg or no treatment were evaluated for the risk of cardiovascular events. This study (JELIS) included 18,645 patients, including men aged 40 to 75 years, and postmenopausal women ≤75 years of age. All patients in the trial had a total serum cholesterol level ≥250 mg/dL, and just over one-third (36%) of patients enrolled had hypertension. Diabetes mellitus and coronary artery disease were comorbidities in 15% and 20% of enrolled patients, respectively.

Background therapies in the JELIS trial included the statins pravastatin 10 mg daily and simvastatin 5 mg daily. Patients in the active treatment group received EPA at a daily dose of 1800 mg available in Japan as a highly purified fish oil derivative containing >98% EPA (trade name: Epadel). Baseline levels of triglyceride levels and LDL-C were 275 mg/dL and 180 mg/dL, respectively.

Treatment with statin plus EPA versus a statin alone decreased both metrics by a similar margin in both treatment groups (19% with statin therapy alone, and 26% with combination therapy). However, triglyceride levels were reduced 10% in patients receiving combination therapy versus 5% in the statin-only group. Because these results were obtained only with a highly purified form of omega-3 fatty acid, treatment guidelines for management of hypertriglyceridemia recognize differences in formulations of omega-3 fatty acids.

Omega-3 fatty acids are thought to reduce triglyceride levels by influencing expression of a lipoprotein known as apolipoprotein C-III (ApoC-III), which inhibits lipoprotein lipase and hepatic lipase. This inhibitory activity of ApoC-III impairs hepatic uptake of triglyceride-rich lipoproteins. Normally, hepatic uptake of these lipoproteins contributes to hypertriglyceridemia. By upregulating ApoC-III levels, omega-3 fatty acids reduce triglyceride generation and uptake in the liver. In addition, upregulation of ApoC-III through omega-3 fatty acid supplementation may contribute to both insulin resistance and atherosclerosis.

Although pharmacologic therapy is an important treatment in patients with high triglyceride levels, physical activity and weight loss are also critical components of treatment. In overweight or obese patients, some evidence indicates that weight loss may have the greatest effect on improving triglyceride levels. More profound weight loss, however, is required to lower LDL-C levels.

By recognizing the benefits of omega-3 fatty acid therapy, proved both through results of the JELIS trial and through multiple epidemiologic studies, as well as convincing basic pharmacologic evidence, it is important for managed care professionals to recognize the important role of these treatments in patients with hypertriglyceridemia.