TY - JOUR
T1 - Effects of omega-3 carboxylic acids on lipoprotein particles and other cardiovascular risk markers in high-risk statin-treated patients with residual hypertriglyceridemia
T2 - A randomized, controlled, double-blind trial
AU - Dunbar, Richard L.
AU - Nicholls, Stephen J.
AU - Maki, Kevin C.
AU - Roth, Eli M.
AU - Orloff, David G.
AU - Curcio, Danielle
AU - Johnson, Judith
AU - Kling, Douglas
AU - Davidson, Michael H.
N1 - Funding Information:
This trial was funded by AstraZeneca (Wilmington, DE). RD is supported by NIH NHLBI K23HL091130, but has no competing interests to declare. SN has been a consultant for or received honoraria from AbbVie, Anthera, AstraZeneca, Atheronova, Boehringer Ingelheim, CSL Behring, Esperion, Kinemed, Merck, Novo Nordisk, Pfizer, Resverlogix, Roche, Sanofi-Aventis, and Takeda and has received research support from Anthera, AstraZeneca, Eli Lilly, Roche, Novartis, Resverlogix, Karo Bio, LipoScience, and Cerenis. KM declares that he has received consulting fees and research grants from AbbVie, AstraZeneca, Trygg Pharma AS, GlaxoSmithKline, Amarin, and Pharmavite LLC. ER declares that he is a speaker for Amarin and AstraZeneca. DO, representing Medpace, a clinical research organization, has been engaged as a scientific and regulatory advisor to and involved in clinical research collaborations with multiple sponsors working in the lipid metabolism area. DC, JJ, DK, and MD are former employees of Omthera Pharmaceuticals and MD is now employed by AstraZeneca.
Funding Information:
We thank Mary R. Dicklin, PhD, with Midwest Center for Metabolic & Cardiovascular Research, who provided medical writing services. Omthera Pharmaceuticals funded the medical writing support. Dr. Dunbar is supported by NIH NHLBI K23HL091130.
PY - 2015/9/2
Y1 - 2015/9/2
N2 - 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. Conclusion: 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. Trial registration: ClinicalTrials.gov Identifier NCT01408303.
AB - 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. Conclusion: 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. Trial registration: ClinicalTrials.gov Identifier NCT01408303.
KW - Apolipoprotein CIII
KW - Docosahexaenoic acid
KW - Eicosapentaenoic acid
KW - Hypertriglyceridemia
KW - Lipoprotein subclasses
KW - Lipoprotein-associated phospholipase A<inf>2</inf>
KW - Low-density lipoprotein cholesterol
KW - Omega-3 fatty acids
KW - Statin
KW - Triglycerides
UR - http://www.scopus.com/inward/record.url?scp=84940469020&partnerID=8YFLogxK
U2 - 10.1186/s12944-015-0100-8
DO - 10.1186/s12944-015-0100-8
M3 - Article
C2 - 26328624
AN - SCOPUS:84940469020
VL - 14
JO - Lipids in Health and Disease
JF - Lipids in Health and Disease
SN - 1476-511X
IS - 1
M1 - 98
ER -