A highly bioavailable omega-3 free fatty acid formulation improves the cardiovascular risk profile in high-risk, statin-treated patients with residual hypertriglyceridemia (the ESPRIT trial).

Abstract

BACKGROUND:

A novel omega-3 formulation in free fatty acid form (OM3-FFA) has as much as 4-fold greater bioavailability than ethyl ester forms and reduces triglyceride (TG) levels in patients with severe hypertriglyceridemia.

OBJECTIVE:

This study was designed to evaluate the efficacy of adding OM3-FFA (2 or 4 g/d) to statin therapy for lowering non-HDL-C and TG levels in subjects with persistent hypertriglyceridemia and at high risk for cardiovascular disease.

METHODS:

In this double-blind, parallel-group study, 647 diet-stable patients with fasting TG levels ≥ 200 mg/dL and <500 mg/dL (treated with a maximally tolerated dose of statin or statin with ezetimibe) and at high risk for cardiovascular disease were randomized to 6 weeks of treatment with capsules of control (olive oil [OO]) 4 g/d, OM3-FFA 2 g/d (plus 2 g/d OO), or OM3-FFA 4 g/d. Assessments included fasting serum levels of lipids and apolipoproteins (apo); plasma concentrations of eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, and arachidonic acid; and laboratory safety values and adverse events.

RESULTS:

In the 627 subjects in the intention to treat sample, non-HDL-C levels were reduced with OM3-FFA 2 g/d and OM3-FFA 4 g/d (-3.9% and -6.9%, respectively) compared with OO (-0.9%) (both, P < 0.05), as were TG levels (-14.6% and -20.6%, respectively, vs -5.9%; both, P < 0.001). LDL-C levels increased with OM3-FFA 2 g/d (4.6%) compared with OO (1.1%) (P = 0.025) but not with OM3-FFA 4 g/d (1.3%). Total cholesterol and VLDL-C concentrations were reduced compared with OO with both OM3-FFA dosages, and the total cholesterol/HDL-C ratio and apo AI and apo B levels were significantly lowered with OM3-FFA 4 g/d only (all at least P < 0.05). Percent changes from baseline in HDL-C did not differ between OO and either OM3-FFA group. Plasma concentrations of docosahexaenoic acid, eicosapentaenoic acid, and docosapentaenoic acid were significantly increased and arachidonic acid was significantly reduced in both OM3-FFA treatment groups compared with the OO responses (all, P < 0.001). Withdrawals related to treatment-emergent adverse events ranged from 0.9% with OO to 3.2% with OM3-FFA 4 g/d.

CONCLUSIONS:

OM3-FFA was well tolerated and lowered non-HDL-C and TG levels at both 2- and 4-g/d dosages in patients with persistent hypertriglyceridemia taking a statin, with the 4-g/d dosage providing incremental improvements compared with 2 g/d.

• Authors: Kevin C Maki, David G Orloff, Stephen J Nicholls, Richard L Dunbar, Eli M Roth, Danielle Curcio, Judith Johnson, Douglas Kling, Michael H Davidson
• Journal: Clinical therapeutics (Clin Ther) Vol. 35 Issue 9 Pg. 1400-11.e1-3 (Sep 2013) ISSN: 1879-114X [Electronic] United States
• PMID: 23998969 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: © 2013 Elsevier HS Journals, Inc. All rights reserved.

Chemical References

• Cholesterol, HDL
• Fatty Acids, Nonesterified
• Fatty Acids, Omega-3
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Olive Oil
• Plant Oils
• Triglycerides

Topics

• Aged
• Biological Availability
• Cardiovascular Diseases (blood, prevention & control)
• Cholesterol, HDL (blood)
• Combined Modality Therapy
• Dietary Supplements
• Double-Blind Method
• Drug Administration Schedule
• Drug Therapy, Combination
• Fatty Acids, Nonesterified (administration & dosage, adverse effects, therapeutic use)
• Fatty Acids, Omega-3 (administration & dosage, adverse effects, blood, therapeutic use)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Hypertriglyceridemia (blood, complications, drug therapy)
• Medication Adherence
• Middle Aged
• Olive Oil
• Plant Oils (administration & dosage, adverse effects, therapeutic use)
• Risk Factors
• Triglycerides (blood)