Targeting Very High Triglycerides in At-Risk Patients
San Diego—Hypertriglyceridemia is defined as elevated triglyceride concentration in the blood (>150 mg/dL). Common causes of hypertriglyceridemia include genetics, obesity, associated diseases and conditions, medications, and acute alcohol consumption with fatty liver disease. Clinical consequences of elevated triglycerides may include pancreatitis, fatty liver disorder, and cardiovascular disease [CMAJ. 2007;176(8):1113-1120].
Matthew J. Budoff, MD, professor of medicine, David Geffen School of Medicine at the University of California, Los Angeles, discussed the management of hypertriglyceridemia at the AMCP meeting during a science and innovation theater sponsored by Amarin Pharma Inc.
For the treatment of very high triglyerides (≥500 mg/dL), organizations and agencies recommend targeting triglyceride levels to reduce the risk of acute pancreatitis. Approaches to lower triglyceride levels include very low-fat diet, weight reduction, modified alcohol intake, omega-3 poly- unsaturated fatty acids (PUFAs), fibrate, or niacin. If individuals do not reach their target LDL cholesterol goal, clinicians can initiate statin therapy.
“LDL [low-density lipoprotein] control is critical,” he said. “[There is] no doubt that statins work for LDL, but for high triglycerides, statins have only [a] moderate effect. If you lower triglycerides, but increase LDL, you negate a lot of the benefits.”
Any increase in LDL cholesterol is counterproductive to statin therapy. Omega-3 PUFAs containing docosahexaenic acid and fenofibrates may increase LDL cholesterol while lowering very high triglycerides.
Icosapent ethyl—the first FDA-approved eicosapentaenoic acid (EPA)-only omega-3 fatty acid—is an option for the manage- ment of patients with severe hypertriglyceridemia. It is indicated as an adjunct to diet to reduce triglyceride levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. The recommended daily dose is 4 g/day, taken as 2 capsules twice a day with food. Clinicians should assess lipid levels before initiating therapy. They should identify other causes (eg, diabetes mellitus, hypothyroidism, or medications) of high triglyceride levels and manage as appropriate. Clinicians should engage patients in appropriate nutritional intake and physical activity before receiving icosapent ethyl, which should continue during treatment with the medicine. Patients should be advised to swallow icosapent ethyl capsules whole.
MARINE Study
Dr. Budoff highlighted the results from the randomized, placebo-controlled, double-blind, parallel-group MARINE study that evaluated adults patients (n=76 on icosapent ethyl and n=75 on placebo) with fasting triglyceride levels ≥500 mg/dL and ≤2000 mg/dL, with or without statin therapy. The primary end point was the placebo-adjusted median percent change in triglyceride levels from baseline to Week 12. The results found that icosapent ethyl significantly reduced triglyceride levels without increasing LDL cholesterol. A 33% median reduction in triglycerides as compared with placebo in the overall study population was observed. Icosapent ethyl showed a 65% median reduction in triglycerides in patients on stable statin therapy compared with placebo.
Icosapent ethyl also significantly reduced other atherogenic lipid biomarkers: very low-density lipoprotein cholesterol (−29%), non–high-density lipoprotein cholesterol (−18%), and apolipoprotein B (−9%) compared with placebo.
Adverse Reactions
Icosapent ethyl demonstrated a tolerability and side effect profile similar to placebo. The most common adverse reaction (incidence >2% and greater than placebo) was arthralgia. No drug–drug interactions were observed in patients with the following medications: warfarin, omeprazole, atorvastatin, or rosiglitazone. In the MARINE study, the safety and tolerability profile of icosapent ethyl was similar to placebo. No patients taking icosapent ethyl 4 g/day reported eructation, 1% experienced nausea, and 1% experienced diarrhea compared with 4%, 5%, and 7%, respectively, for placebo.
Icosapent ethyl is covered on >95% of all managed care plans, with minimal restrictions on most plans. It is also covered on a majority of Medicare Part D plans, according to Dr. Budoff.
For icosapent ethyl Important Safety Information, please visit www.vascepa.com.—Eileen Koutnik-Fotopoulos
