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)

Clin Ther. 2013 Sep;35(9):1400-11.e1-3. doi: 10.1016/j.clinthera.2013.07.420. Epub 2013 Aug 30.

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.

Trial registration: ClinicalTrials.gov NCT01408303.

Keywords: LDL-C; hypertriglyceridemia; omega-3 fatty acids; statins; triglycerides.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

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

Substances

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

Associated data

  • ClinicalTrials.gov/NCT01408303