Serebruany Victor L, Miller Michael, Pokov Alex N, Lynch Donald, Jensen Jesper K, Hallén Jonas, Atar Dan
HeartDrug™ Research LLC, Johns Hopkins University, Towson, Md., USA. Heartdrug @ aol.com
Cardiology. 2011;118(3):187-94. doi: 10.1159/000329300. Epub 2011 Jun 22.
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.
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.
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.
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.
已对处方用ω-3酸乙酯（PO-3A）在冠状动脉疾病（CAD）、心律失常和心力衰竭患者中的疗效益处进行了测试。一些证据表明，PO-3A可能通过抑制血小板发挥其益处。我们检验了这一假设，即PO-3A在已确诊的稳定CAD患者中可能抑制血小板活性，其作用超出了阿司匹林和他汀类药物的抗血小板特性。
30例已确诊CAD且甘油三酯超过250mg/dl、接受阿司匹林（70 - 160mg/日）和他汀类药物（辛伐他汀等效剂量：5 - 40mg/日）治疗的患者，按1:1:1随机分为三组，分别给予每日1g奥米加-3脂肪酸乙酯（DHA/EPA比例1.25:1.0）、每日2g奥米加-3脂肪酸乙酯或安慰剂，疗程为2周。在基线以及PO-3A治疗后1周和2周进行血小板检测，包括血小板聚集测定、流式细胞术以及盒式分析仪读数。
PO-3A治疗后，二磷酸腺苷（ADP）诱导的血小板聚集（p = 0.037）、糖蛋白IIb/IIIa抗原（p = 0.031）和活性（p = 0.024）以及P-选择素（p = 0.041）均显著降低，而血小板/内皮细胞黏附分子（p = 0.09）、玻连蛋白受体（p = 0.16）、血小板-单核细胞微粒形成（p = 0.19）以及VerifyNow IIb/IIIa检测（p = 0.27）仅呈现出提示血小板活性降低的非显著趋势。最后，胶原和花生四烯酸诱导的聚集、PFA-100装置的闭合时间以及血小板反应蛋白（CD36）、糖蛋白Ib（CD42b）、溶酶体相关膜蛋白3（CD63）、溶酶体相关膜蛋白1（CD107a）、CD40配体（CD154）、糖蛋白37（CD165）以及蛋白酶激活受体-1完整（SPAN 12）和裂解（WEDE-15）表位的表达不受PO-3A 2周治疗的影响。
与安慰剂相比，尽管同时使用了阿司匹林和他汀类药物，但PO-3A短期治疗独立于剂量且在1周时就能适度降低血小板活性生物标志物。PO-3A的作用是独特的，不同于其他已知的抗血小板药物，提示可能存在多效性。这些初步的随机数据需要在前瞻性研究中得到证实。
