Early impact of prescription Omega-3 fatty acids on platelet biomarkers in patients with coronary artery disease and hypertriglyceridemia

Victor L Serebruany, Michael Miller, Alex N Pokov, Donald Lynch, Jesper K Jensen, Jonas Hallén, Dan Atar

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Background: Prescription omega-3-acid ethyl esters (PO-3A) have been tested for outcome benefits in patients with coronary artery disease (CAD), arrhythmias and heart failure. Some evidence suggests that PO-3A may exert their benefit via inhibiting platelets. We tested the hypothesis that PO-3A may inhibit platelet activity in patients with documented stable CAD, beyond the antiplatelet properties of aspirin and statins. Methods: Thirty patients with documented CAD and triglycerides over 250 mg/dl treated with aspirin (70-160 mg/daily) and statins (simvastatin equivalence dose: 5-40 mg/daily) were randomized 1:1:1 to Omacor™ 1 g/day (DHA/EPA ratio 1.25:1.0), Omacor 2 g/day, or a placebo for 2 weeks. Platelet tests including aggregometry and flow cytometry and cartridge analyzer readings were performed at baseline and at 1 and 2 weeks following PO-3A therapy. Results: ADP-induced platelet aggregation (p = 0.037), GP IIb/IIIa antigen (p = 0.031) and activity (p = 0.024), and P-selectin (p = 0.041) were significantly reduced after PO-3A, while platelet/endothelial cell adhesion molecule (p = 0.09), vitronectin receptor (p = 0.16), formation of platelet-monocyte microparticles (p = 0.19) and the VerifyNow IIb/IIIa test (p = 0.27) only exhibited nonsignificant trends suggestive of reduced platelet activity. Finally, collagen- and arachidonic acid-induced aggregation, closure time with the PFA-100 device and expression of thrombospondin (CD36), GP Ib (CD42b), LAMP-3 (CD63), LAMP-1 (CD107a), CD40-ligand (CD154), GP37 (CD165), and PAR-1 receptor intact (SPAN 12) and cleaved (WEDE-15) epitopes were not affected by 2 weeks of PO-3A. Conclusion: Independently of the dose and already at 1 week, short-term therapy with PO-3A provided a modest reduction of platelet activity biomarkers, despite concomitant aspirin and statin therapy, when compared to a placebo. The effect of PO-3A is unique, differs from other known antiplatelet agents and suggests potential pleiotropism. These preliminary randomized data call for confirmation in prospective studies.
OriginalsprogEngelsk
TidsskriftCardiology
Vol/bind118
Udgave nummer3
Sider (fra-til)187-194
ISSN0008-6312
DOI
StatusUdgivet - 2011

Fingeraftryk

Hypertriglyceridemia
Omega-3 Fatty Acids
Prescriptions
Coronary Artery Disease
Esters
Acids
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Integrin alphaVbeta3
Placebos
Platelet Membrane Glycoprotein IIb
CD40 Ligand
P-Selectin
Simvastatin
Platelet Aggregation Inhibitors
Platelet Aggregation
Arachidonic Acid
Reading
Flow Cytometry
Prospective Studies
Equipment and Supplies

Citer dette

Serebruany, Victor L ; Miller, Michael ; Pokov, Alex N ; Lynch, Donald ; Jensen, Jesper K ; Hallén, Jonas ; Atar, Dan. / Early impact of prescription Omega-3 fatty acids on platelet biomarkers in patients with coronary artery disease and hypertriglyceridemia. I: Cardiology. 2011 ; Bind 118, Nr. 3. s. 187-194.
@article{cafb65b1bc82460d8181944690cfe30d,
title = "Early impact of prescription Omega-3 fatty acids on platelet biomarkers in patients with coronary artery disease and hypertriglyceridemia",
abstract = "Background: Prescription omega-3-acid ethyl esters (PO-3A) have been tested for outcome benefits in patients with coronary artery disease (CAD), arrhythmias and heart failure. Some evidence suggests that PO-3A may exert their benefit via inhibiting platelets. We tested the hypothesis that PO-3A may inhibit platelet activity in patients with documented stable CAD, beyond the antiplatelet properties of aspirin and statins. Methods: Thirty patients with documented CAD and triglycerides over 250 mg/dl treated with aspirin (70-160 mg/daily) and statins (simvastatin equivalence dose: 5-40 mg/daily) were randomized 1:1:1 to Omacor™ 1 g/day (DHA/EPA ratio 1.25:1.0), Omacor 2 g/day, or a placebo for 2 weeks. Platelet tests including aggregometry and flow cytometry and cartridge analyzer readings were performed at baseline and at 1 and 2 weeks following PO-3A therapy. Results: ADP-induced platelet aggregation (p = 0.037), GP IIb/IIIa antigen (p = 0.031) and activity (p = 0.024), and P-selectin (p = 0.041) were significantly reduced after PO-3A, while platelet/endothelial cell adhesion molecule (p = 0.09), vitronectin receptor (p = 0.16), formation of platelet-monocyte microparticles (p = 0.19) and the VerifyNow IIb/IIIa test (p = 0.27) only exhibited nonsignificant trends suggestive of reduced platelet activity. Finally, collagen- and arachidonic acid-induced aggregation, closure time with the PFA-100 device and expression of thrombospondin (CD36), GP Ib (CD42b), LAMP-3 (CD63), LAMP-1 (CD107a), CD40-ligand (CD154), GP37 (CD165), and PAR-1 receptor intact (SPAN 12) and cleaved (WEDE-15) epitopes were not affected by 2 weeks of PO-3A. Conclusion: Independently of the dose and already at 1 week, short-term therapy with PO-3A provided a modest reduction of platelet activity biomarkers, despite concomitant aspirin and statin therapy, when compared to a placebo. The effect of PO-3A is unique, differs from other known antiplatelet agents and suggests potential pleiotropism. These preliminary randomized data call for confirmation in prospective studies.",
keywords = "Aged, Biological Markers, Coronary Artery Disease, Docosahexaenoic Acids, Double-Blind Method, Drug Combinations, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Female, Humans, Hypertriglyceridemia, Male, Middle Aged, Platelet Activation, Platelet Function Tests, Platelet Membrane Glycoproteins",
author = "Serebruany, {Victor L} and Michael Miller and Pokov, {Alex N} and Donald Lynch and Jensen, {Jesper K} and Jonas Hall{\'e}n and Dan Atar",
note = "Copyright {\circledC} 2011 S. Karger AG, Basel.",
year = "2011",
doi = "10.1159/000329300",
language = "English",
volume = "118",
pages = "187--194",
journal = "Cardiology",
issn = "0008-6312",
publisher = "S. Karger AG",
number = "3",

}

Early impact of prescription Omega-3 fatty acids on platelet biomarkers in patients with coronary artery disease and hypertriglyceridemia. / Serebruany, Victor L; Miller, Michael; Pokov, Alex N; Lynch, Donald; Jensen, Jesper K; Hallén, Jonas; Atar, Dan.

I: Cardiology, Bind 118, Nr. 3, 2011, s. 187-194.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Early impact of prescription Omega-3 fatty acids on platelet biomarkers in patients with coronary artery disease and hypertriglyceridemia

AU - Serebruany, Victor L

AU - Miller, Michael

AU - Pokov, Alex N

AU - Lynch, Donald

AU - Jensen, Jesper K

AU - Hallén, Jonas

AU - Atar, Dan

N1 - Copyright © 2011 S. Karger AG, Basel.

PY - 2011

Y1 - 2011

N2 - Background: Prescription omega-3-acid ethyl esters (PO-3A) have been tested for outcome benefits in patients with coronary artery disease (CAD), arrhythmias and heart failure. Some evidence suggests that PO-3A may exert their benefit via inhibiting platelets. We tested the hypothesis that PO-3A may inhibit platelet activity in patients with documented stable CAD, beyond the antiplatelet properties of aspirin and statins. Methods: Thirty patients with documented CAD and triglycerides over 250 mg/dl treated with aspirin (70-160 mg/daily) and statins (simvastatin equivalence dose: 5-40 mg/daily) were randomized 1:1:1 to Omacor™ 1 g/day (DHA/EPA ratio 1.25:1.0), Omacor 2 g/day, or a placebo for 2 weeks. Platelet tests including aggregometry and flow cytometry and cartridge analyzer readings were performed at baseline and at 1 and 2 weeks following PO-3A therapy. Results: ADP-induced platelet aggregation (p = 0.037), GP IIb/IIIa antigen (p = 0.031) and activity (p = 0.024), and P-selectin (p = 0.041) were significantly reduced after PO-3A, while platelet/endothelial cell adhesion molecule (p = 0.09), vitronectin receptor (p = 0.16), formation of platelet-monocyte microparticles (p = 0.19) and the VerifyNow IIb/IIIa test (p = 0.27) only exhibited nonsignificant trends suggestive of reduced platelet activity. Finally, collagen- and arachidonic acid-induced aggregation, closure time with the PFA-100 device and expression of thrombospondin (CD36), GP Ib (CD42b), LAMP-3 (CD63), LAMP-1 (CD107a), CD40-ligand (CD154), GP37 (CD165), and PAR-1 receptor intact (SPAN 12) and cleaved (WEDE-15) epitopes were not affected by 2 weeks of PO-3A. Conclusion: Independently of the dose and already at 1 week, short-term therapy with PO-3A provided a modest reduction of platelet activity biomarkers, despite concomitant aspirin and statin therapy, when compared to a placebo. The effect of PO-3A is unique, differs from other known antiplatelet agents and suggests potential pleiotropism. These preliminary randomized data call for confirmation in prospective studies.

AB - Background: Prescription omega-3-acid ethyl esters (PO-3A) have been tested for outcome benefits in patients with coronary artery disease (CAD), arrhythmias and heart failure. Some evidence suggests that PO-3A may exert their benefit via inhibiting platelets. We tested the hypothesis that PO-3A may inhibit platelet activity in patients with documented stable CAD, beyond the antiplatelet properties of aspirin and statins. Methods: Thirty patients with documented CAD and triglycerides over 250 mg/dl treated with aspirin (70-160 mg/daily) and statins (simvastatin equivalence dose: 5-40 mg/daily) were randomized 1:1:1 to Omacor™ 1 g/day (DHA/EPA ratio 1.25:1.0), Omacor 2 g/day, or a placebo for 2 weeks. Platelet tests including aggregometry and flow cytometry and cartridge analyzer readings were performed at baseline and at 1 and 2 weeks following PO-3A therapy. Results: ADP-induced platelet aggregation (p = 0.037), GP IIb/IIIa antigen (p = 0.031) and activity (p = 0.024), and P-selectin (p = 0.041) were significantly reduced after PO-3A, while platelet/endothelial cell adhesion molecule (p = 0.09), vitronectin receptor (p = 0.16), formation of platelet-monocyte microparticles (p = 0.19) and the VerifyNow IIb/IIIa test (p = 0.27) only exhibited nonsignificant trends suggestive of reduced platelet activity. Finally, collagen- and arachidonic acid-induced aggregation, closure time with the PFA-100 device and expression of thrombospondin (CD36), GP Ib (CD42b), LAMP-3 (CD63), LAMP-1 (CD107a), CD40-ligand (CD154), GP37 (CD165), and PAR-1 receptor intact (SPAN 12) and cleaved (WEDE-15) epitopes were not affected by 2 weeks of PO-3A. Conclusion: Independently of the dose and already at 1 week, short-term therapy with PO-3A provided a modest reduction of platelet activity biomarkers, despite concomitant aspirin and statin therapy, when compared to a placebo. The effect of PO-3A is unique, differs from other known antiplatelet agents and suggests potential pleiotropism. These preliminary randomized data call for confirmation in prospective studies.

KW - Aged

KW - Biological Markers

KW - Coronary Artery Disease

KW - Docosahexaenoic Acids

KW - Double-Blind Method

KW - Drug Combinations

KW - Eicosapentaenoic Acid

KW - Fatty Acids, Omega-3

KW - Female

KW - Humans

KW - Hypertriglyceridemia

KW - Male

KW - Middle Aged

KW - Platelet Activation

KW - Platelet Function Tests

KW - Platelet Membrane Glycoproteins

U2 - 10.1159/000329300

DO - 10.1159/000329300

M3 - Journal article

C2 - 21701167

VL - 118

SP - 187

EP - 194

JO - Cardiology

JF - Cardiology

SN - 0008-6312

IS - 3

ER -