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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: HeartDrug™ Research LLC, Johns Hopkins University, Towson, Md., USA. Heartdrug @ aol.com
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
authors.forename: Michael
authors.initials: M
authors.lastname: Miller
authors.forename: Alex N
authors.initials: AN
authors.lastname: Pokov
authors.forename: Donald
authors.initials: D
authors.lastname: Lynch
authors.forename: Jesper K
authors.initials: JK
authors.lastname: Jensen
authors.forename: Jonas
authors.initials: J
authors.lastname: Hallén
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000502:physiology; D010979:Platelet Function Tests; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D004338:Drug Combinations; D015525:Fatty Acids, Omega-3; D010980:Platelet Membrane Glycoproteins; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C405603:Omacor