Effects of omega-3 carboxylic acids on lipoprotein particles and other cardiovascular risk markers in high-risk statin-treated patients with residual hypertriglyceridemia: a randomized, controlled, double-blind trial.
BACKGROUND
This study examined the effects of a mixture of highly bioavailable omega-3 carboxylic acids (OM3-CA) on nuclear magnetic resonance spectroscopy-assessed lipoprotein particle concentrations and sizes and other cardiovascular risk markers in statin-treated patients with fasting triglycerides (TG) ≥ 2.3 mmol/L (200 mg/dL) and <5.6 mmol/L (500 mg/dL) and at high cardiovascular risk.


METHODS
After a diet lead-in and statin-stabilization period, 647 patients were randomly assigned to receive capsules of control (olive oil, OO) 4 g/d, OM3-CA 2 g/d (plus OO 2 g/d), or OM3-CA 4 g/d for 6 weeks.


RESULTS
Compared with OO, low-density lipoprotein (LDL) particle size was increased with OM3-CA 2 g/d (p < 0.01) and 4 g/d (p < 0.001), and very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) particle sizes were decreased with both OM3-CA dosages vs. OO (p < 0.001 and p < 0.05 for VLDL and HDL, respectively). Total VLDL/chylomicron remnant particle concentration was reduced by 8.5 and 16.0 % with OM3-CA 2 and 4 g/d, respectively, vs. a 6.9 % reduction with OO (p < 0.001 for OM3-CA 4 g/d vs. OO). Total HDL particle concentration was also reduced by 1.5 and 3.2 % with OM3-CA 2 and 4 g/d, respectively, vs. a 0.6 % increase with OO (at least p < 0.05 for both comparisons). Changes in total LDL particle concentration were not significantly different for OO vs. OM3-CA at either dosage. Apolipoprotein (Apo) CIII levels decreased by 7.6 and 13.1 % with OM3-CA 2 and 4 g/d, respectively, vs. 3.2 % with OO (p < 0.001 for OM3-CA 4 g/d vs. OO). Lipoprotein-associated phospholipase A2 (Lp-PLA2) mass was reduced by 6.2 and 10.7 % with OM3-CA 2 and 4 g/d, respectively, vs. a 0.1 % increase with OO (p < 0.001 for both vs. OO). There were no significant differences between treatments in high-sensitivity C-reactive protein responses.


CONCLUSIONS
OM3-CA were associated with shifts in lipoprotein particle sizes and concentrations, and reductions in Apo CIII and Lp-PLA2, in patients with hypertriglyceridemia while taking a statin.


BACKGROUND
ClinicalTrials.gov Identifier NCT01408303.
Division of Translational Medicine & Human Genetics, Perelman School of Medicine at the University of Pennsylvania, 3600 Spruce Street, 8046 Maloney Building, Philadelphia, PA, 19104-2699, USA. richard.dunbar@uphs.upenn.edu.
Richard L
RL
Dunbar
South Australian Health & Medical Research Institute, University of Adelaide, Adelaide, Australia. stephen.nicholls@sahmri.com.
Stephen J
SJ
Nicholls
Midwest Center for Metabolic & Cardiovascular Research, Chicago, IL, USA. kmaki@mc-mcr.com.
Kevin C
KC
Maki
Sterling Research Group, Cincinnati, OH, USA. eroth@sterlingresearch.org.
Eli M
EM
Roth
Medpace, Inc., Cincinnati, OH, USA. d.orloff@medpace.com.
David G
DG
Orloff
Omthera Pharmaceuticals, Princeton, NJ, USA. dcurcio319@gmail.com.
Danielle
D
Curcio
Omthera Pharmaceuticals, Princeton, NJ, USA. judithbjohnson@gmail.com.
Judith
J
Johnson
Omthera Pharmaceuticals, Princeton, NJ, USA. douglaskling@gmail.com.
Douglas
D
Kling
Omthera Pharmaceuticals, Princeton, NJ, USA. mdavidson@omthera.com.|AstraZeneca, Wilmington, DE, USA. mdavidson@omthera.com.
Michael H
MH
Davidson
D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D053305:Apolipoprotein C-III / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000473:pathology / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D053298:Chylomicron Remnants / Q000097:blood; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015228:Hypertriglyceridemia / Q000097:blood / Q000178:diet therapy* / Q000188:drug therapy* / Q000473:pathology; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D000069463:Olive Oil / Q000008:administration & dosage; D054467:Phospholipases A2 / Q000097:blood; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D053305:Apolipoprotein C-III; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D053298:Chylomicron Remnants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008075:Lipoproteins, HDL; D000069463:Olive Oil; D014280:Triglycerides; D004281:Docosahexaenoic Acids; D002097:C-Reactive Protein; D015118:Eicosapentaenoic Acid; D054467:Phospholipases A2