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多不饱和ω-3 脂肪酸对经皮冠状动脉介入治疗患者双联抗血小板治疗反应性的影响:OMEGA-PCI 研究(经皮冠状动脉介入治疗后ω-3 脂肪酸改变双联抗血小板治疗反应性研究)。

Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the OMEGA-PCI (OMEGA-3 fatty acids after pci to modify responsiveness to dual antiplatelet therapy) study.

机构信息

Department of Coronary Disease, John Paul II Hospital, Cracow, Poland.

出版信息

J Am Coll Cardiol. 2010 Apr 20;55(16):1671-8. doi: 10.1016/j.jacc.2009.11.080.

Abstract

OBJECTIVES

The purpose of this study was to investigate whether omega-3 polyunsaturated fatty acids (PUFAs) are able to modify platelet responsiveness to dual antiplatelet therapy in stable coronary artery disease patients undergoing percutaneous coronary intervention (PCI).

BACKGROUND

Although previous studies have suggested antiplatelet properties of omega-3 polyunsaturated fatty acids, it is unknown whether they can enhance platelet inhibition on standard aspirin and clopidogrel treatment.

METHODS

The OMEGA-PCI (OMEGA-3 Fatty Acids After PCI to Modify Responsiveness to Dual Antiplatelet Therapy) study was an investigator-initiated, prospective, single-center, double-blind, placebo-controlled, randomized study. Patients receiving standard dual antiplatelet therapy (aspirin 75 mg/day and clopidogrel 600 mg loading dose followed by 75 mg/day) were randomly assigned to receive the addition of 1 g of omega-3 ethyl esters (n = 33) or placebo (n = 30) for 1 month. Platelet function was measured serially by light transmission aggregometry (adenosine diphosphate and arachidonic acid [AA] were used as agonists) and assessment of the phosphorylation status of the vasodilator-stimulated phosphoprotein at baseline, 12 h, 3 to 5 days, and 30 days after randomization.

RESULTS

The P2Y(12) reactivity index was significantly lower, by 22.2%, after 1 month of treatment with omega-3 polyunsaturated fatty acids compared with placebo when used in addition to dual antiplatelet therapy (p = 0.020). Maximal platelet aggregation induced by 5 and 20 micromol/l adenosine diphosphate was lower by 13.3% (p = 0.026) and 9.8% (p = 0.029), respectively, after 1 month of treatment with omega-3 polyunsaturated fatty acids compared with placebo. Platelet aggregation after AA stimulation was low and did not change significantly throughout the study. There were no cases of aspirin resistance during follow-up that was suggestive of good compliance with the medication.

CONCLUSIONS

The addition of omega-3 ethyl esters to the combination of aspirin and clopidogrel significantly potentiates platelet response to clopidogrel after percutaneous coronary intervention.

摘要

目的

本研究旨在探讨 omega-3 多不饱和脂肪酸(PUFA)是否能够改变经皮冠状动脉介入治疗(PCI)后稳定型冠状动脉疾病患者对双联抗血小板治疗的血小板反应性。

背景

尽管先前的研究表明 omega-3 多不饱和脂肪酸具有抗血小板作用,但尚不清楚它们是否能够增强对标准阿司匹林和氯吡格雷治疗的血小板抑制作用。

方法

OMEGA-PCI(经皮冠状动脉介入治疗后 omega-3 脂肪酸改变双联抗血小板治疗反应性)研究是一项由研究者发起的、前瞻性的、单中心的、双盲的、安慰剂对照的、随机研究。接受标准双联抗血小板治疗(阿司匹林 75mg/天,氯吡格雷 600mg 负荷剂量,随后 75mg/天)的患者被随机分配接受 1g omega-3 乙酯(n=33)或安慰剂(n=30)治疗 1 个月。通过透光比浊法(使用二磷酸腺苷和花生四烯酸[AA]作为激动剂)连续测量血小板功能,并在随机分组后基线、12 小时、3-5 天和 30 天评估磷酸化的血管扩张刺激磷蛋白的状态。

结果

与安慰剂相比,omega-3 多不饱和脂肪酸治疗 1 个月后,P2Y12 反应指数显著降低,降低了 22.2%(p=0.020)。5μmol/l 和 20μmol/l 二磷酸腺苷诱导的最大血小板聚集分别降低了 13.3%(p=0.026)和 9.8%(p=0.029)。AA 刺激后的血小板聚集较低,整个研究过程中无明显变化。在随访期间没有阿司匹林抵抗的病例,表明患者对药物的依从性良好。

结论

在阿司匹林和氯吡格雷联合治疗的基础上添加 omega-3 乙酯可显著增强经皮冠状动脉介入治疗后氯吡格雷对血小板的反应性。

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