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与氯吡格雷相比,替格瑞洛可提高急性冠脉综合征患者的内皮祖细胞水平:一项前瞻性随机研究。

Ticagrelor increases endothelial progenitor cell level compared to clopidogrel in acute coronary syndromes: A prospective randomized study.

作者信息

Bonello Laurent, Frere Corinne, Cointe Sylvie, Laine Marc, Mancini Julien, Thuny Franck, Kerbaul François, Lemesle Gilles, Paganelli Franck, Guieu Regis, Arnaud Laurent, Dignat-George Françoise, Sabatier Florence

机构信息

Service de Cardiologie, Centre Hospitalier Universitaire de Marseille, Hôpital NORD, Aix-Marseille Université, France; Vascular Research Center of Marseille, INSERM UMR-S 1076, Aix-Marseille Université, Marseille, France.

Vascular Research Center of Marseille, INSERM UMR-S 1076, Aix-Marseille Université, Marseille, France.

出版信息

Int J Cardiol. 2015;187:502-7. doi: 10.1016/j.ijcard.2015.03.414. Epub 2015 Mar 31.

Abstract

BACKGROUND

The clinical benefit of ticagrelor compared to clopidogrel in ACS patients suggested off-target property. Such pleiotropic effect could be mediated by circulating endothelial progenitor cells (EPC) which are critical for vascular healing. We aimed to investigate the impact of ticagrelor on EPC in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).

METHODS

We prospectively randomized 106 ACS patients to ticagrelor or clopidogrel. Sub-populations of CD34+ circulating progenitor cells (PC) were analyzed by flow cytometry allowing one to determine the levels of CD34+ PC, CD34+CD45+ Hematopoietic PC, CD34+133+ immature PC and CD34+KDR+ EPC on admission and at 1 month. Changes in PC level were calculated as the difference between 1 month and baseline value.

RESULTS

The 2 groups were similar regarding baseline characteristics including PC numbers on admission. The 2 groups had similar change in overall CD34+ PC and hematopoietic CD34+45+ PC level (p=0.2). On the contrary, when considering CD34+133+ PC and CD34+KDR+ EPC, we observed that patients treated by ticagrelor had a significantly higher increase in levels of these PC subtypes compared to those treated by clopidogrel (0.23 (-0.33; 0.79) vs 0.00 (-0.5; 0.34); p=0.04 and 0.01 (-0.04; 0.05) vs -0.01 (-0.06; 0.03); p=0.02). Changes in the level of CD34+CD133+ PC correlated with platelet activity measured by the VASP index (r=-0.30; p=0.008). By contrast the increase in the level of CD34+KDR+ EPC in the ticagrelor group was independent of platelet activity.

CONCLUSIONS

Ticagrelor increases the number of EPC in ACS patients suggesting a benefit on endothelial regeneration that may participate in the pleiotropic property of the drug.

摘要

背景

与氯吡格雷相比,替格瑞洛在急性冠状动脉综合征(ACS)患者中的临床获益提示其存在脱靶效应。这种多效性作用可能由循环内皮祖细胞(EPC)介导,而EPC对血管愈合至关重要。我们旨在研究替格瑞洛对接受经皮冠状动脉介入治疗(PCI)的急性冠状动脉综合征(ACS)患者EPC的影响。

方法

我们将106例ACS患者前瞻性随机分为替格瑞洛组或氯吡格雷组。通过流式细胞术分析CD34 +循环祖细胞(PC)的亚群,以确定入院时和1个月时CD34 + PC、CD34 + CD45 +造血PC、CD34 + 133 +未成熟PC和CD34 + KDR + EPC的水平。PC水平的变化计算为1个月时的值与基线值之间的差值。

结果

两组在基线特征(包括入院时的PC数量)方面相似。两组在总体CD34 + PC和造血CD34 + 45 + PC水平上的变化相似(p = 0.2)。相反,在考虑CD34 + 133 + PC和CD34 + KDR + EPC时,我们观察到与氯吡格雷治疗的患者相比,替格瑞洛治疗的患者这些PC亚型的水平升高显著更高(0.23(-0.33;0.79)对0.00(-0.5;0.34);p = 0.04和0.01(-0.04;0.05)对-0.01(-0.06;0.03);p = 0.02)。CD34 + CD133 + PC水平的变化与通过VASP指数测量的血小板活性相关(r = -0.30;p = 0.008)。相比之下,替格瑞洛组中CD34 + KDR + EPC水平的升高与血小板活性无关。

结论

替格瑞洛增加了ACS患者的EPC数量,提示其对内皮再生有益,这可能参与了该药物的多效性作用。

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