title: Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: the EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial.
abstract: BACKGROUND
  Omega-3 fatty acids in free fatty acid form have enhanced bioavailability, and plasma levels are less influenced by food than for ethyl ester forms.
  
  
  OBJECTIVE
  The aim was to evaluate the safety and lipid-altering efficacy in subjects with severe hypertriglyceridemia of an investigational pharmaceutical omega-3 free fatty acid (OM3-FFA) containing eicosapentaenoic acid and docosahexaenoic acid.
  
  
  METHODS
  This was a multinational, double-blind, randomized, out-patient study. Men and women with triglycerides (TGs) ≥ 500 mg/dL, but <2000 mg/dL, took control (olive oil [OO] 4 g/d; n = 99), OM3-FFA 2 g/d (plus OO 2 g/d; n = 100), OM3-FFA 3 g/d (plus OO 1 g/d; n = 101), or OM3-FFA 4 g/d (n = 99) capsules for 12 weeks in combination with the National Cholesterol Education Program Therapeutic Lifestyle Changes diet.
  
  
  RESULTS
  Fasting serum TGs changed from baseline by -25.9% (P < .01 vs OO), -25.5% (P < .01 vs OO), and -30.9% (P < .001 vs OO) with 2, 3, and 4 g/d OM3-FFA, respectively, compared with -4.3% with OO. Non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol-to-HDL-C ratio, very low-density lipoprotein cholesterol, remnant-like particle cholesterol, apolipoprotein CIII, lipoprotein-associated phospholipase A2, and arachidonic acid were significantly lowered (P < .05 at each OM3-FFA dosage vs OO); and plasma eicosapentaenoic acid and docosahexaenoic acid were significantly elevated (P < .001 at each OM3-FFA dosage vs OO). With OM3-FFA 2 and 4 g/d (but not 3 g/d), low-density lipoprotein cholesterol was significantly increased compared with OO (P < .05 vs OO). High-sensitivity C-reactive protein responses with OM3-FFA did not differ significantly from the OO response at any dosage. Fewer subjects reported any adverse event with OO vs OM3-FFA, but frequencies across dosage groups were similar. Discontinuation due to adverse event, primarily gastrointestinal, ranged from 5% to 7% across OM3-FFA dosage groups vs 0% for OO.
  
  
  CONCLUSIONS
  OM3-FFA achieved the primary end point for TG lowering and secondary end point of non-HDL-C lowering at 2, 3, and 4 g/d in persons with severe hypertriglyceridemia. This trial was registered at www.clinicaltrials.gov as NCT01242527.
authors: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. Electronic address: j.j.kastelein@amc.uva.nl.
authors: John J P
authors: JJ
authors: Kastelein
authors: Biofortis Clinical Research, Addison, IL, USA.
authors: Kevin C
authors: KC
authors: Maki
authors: Russian Cardiology Scientific Production Complex, Federal State University, Moscow, Russian Federation.
authors: Andrey
authors: A
authors: Susekov
authors: Russian Cardiology Scientific Production Complex, Federal State University, Moscow, Russian Federation.
authors: Marat
authors: M
authors: Ezhov
authors: Copenhagen University Hospital, University of Copenhagen, Herlev, Denmark.
authors: Borge G
authors: BG
authors: Nordestgaard
authors: Omthera Pharmaceuticals, Inc, Princeton, NJ, USA.
authors: Ben N
authors: BN
authors: Machielse
authors: Omthera Pharmaceuticals, Inc, Princeton, NJ, USA.
authors: Douglas
authors: D
authors: Kling
authors: Omthera Pharmaceuticals, Inc, Princeton, NJ, USA.
authors: Michael H
authors: MH
authors: Davidson
mesh_terms: D023381:Endpoint Determination; D015525:Fatty Acids, Omega-3 / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood*
chemical_list: D015525:Fatty Acids, Omega-3; D014280:Triglycerides
keywords: Hypertriglyceridemia; Low-density lipoprotein cholesterol; Omega-3 fatty acids; Remnants; Treatment; Triglycerides