在高敏C反应蛋白和可溶性CD40配体水平升高的急性冠脉综合征患者中，阿司匹林联合氯吡格雷与单用阿司匹林对早期血小板活化影响的随机对照研究

Randomized comparison of the effects of ASA plus clopidogrel versus ASA alone on early platelet activation in acute coronary syndromes with elevated high-sensitivity C-reactive protein and soluble CD40 ligand levels.

作者信息

Vavuranakis Manolis, Latsios George, Aggelis Dimitris, Bosinakou Irini, Karambelas Ioannis, Tousoulis Dimitrios, Toutouzas Kostas, Stefanadis Christodoulos

机构信息

First Department of Cardiology, University of Athens, and Department of Hematology, Hippokration Hospital, Athens, Greece.

出版信息

Clin Ther. 2006 Jun;28(6):860-71. doi: 10.1016/j.clinthera.2006.06.010.

DOI:10.1016/j.clinthera.2006.06.010

PMID:16860169

Abstract

BACKGROUND

High-sensitivity C-reactive protein (hsCRP) and soluble cluster of differentiation 40 ligand (sCD40L) have been established as effective markers of inflammation in predicting the risk for adverse outcomes in patients with acute coronary syndromes (ACSs). Activated platelets secrete certain inflammatory mediators such as P-selectin and sCD40L, which play a role in the pathogenesis of ACSs. Although acetylsalicylic acid (ASA) has been found to be an effective treatment of ACSs, the addition of clopidogrel bisulfate has been found tofurther improve clinical outcomes as a result of additional antiplatelet and anti-inflammatory action. Few data exist concerning the effects of dual antiplatelet therapy on these markers in patients with ACSs.

OBJECTIVE

The aim of this study was to assess the effectiveness and clinical significance of clopidogrel administration in patients with ACSs without ST segment elevation treated with ASA.

METHODS

This randomized, single-blind, controlled trial was conducted at the First Department of Cardiology, Hippokration Hospital, Athens, Greece. Inpatients aged>or=21 years with ACSs without ST segment elevation were randomly assigned to 1 of 2 groups: ASA 325 mg/d for 1 week, followed by ASA (100 mg/d) plus clopidogrel (300-mg loading dose followed by 100 mg/d) for 36 weeks (ASA+Clop group) or ASA alone (325 mg/d for 1 week, followed by 75 mg/d for 36 weeks) (ASA group). Levels of serum sCD40L, hsCRP, and P-selectin were determined on admission and at 8 hours, 48 hours, and 6 days of treatment. By means of clinical follow-up, Kaplan-Meier free-of-major adverse cardiovascular events (MACES) plots were used to assess the prevalence of MACES, including cardiovascular-related death, in patients with and without high levels of hsCRP (>or=3 mg/L) and sCD40L (>or=5 microg/L) for 52 weeks.

RESULTS

A total of 86 patients were enrolled (71 men, 15 women; mean [SD] age, 68 [3] years; mean [SD] weight, 86 [18] kg; white race, 86 [100%]; 43 patients per group). Both groups had similar initial clinical characteristics and P-selectin levels. Baseline hsCRP and sCD40L levels were correlated with baseline P-selectin levels (hsCRP, r2=0.099

CONCLUSIONS

The results of this small study suggest that early activation of platelets, as measured using P-selectin levels, was effectively inhibited by the addition of clopidogrel to a regimen of ASA in the subgroup of patients with ACSs and intense activation of platelets (defined as high hsCRP and sCD40L levels). In patients without high hsCRP and sCD40L levels, the addition of clopidogrel did not have a significant effect on P-selectin levels.

摘要

背景

高敏C反应蛋白（hsCRP）和可溶性分化簇40配体（sCD40L）已被确立为炎症的有效标志物，可用于预测急性冠状动脉综合征（ACS）患者发生不良结局的风险。活化的血小板会分泌某些炎症介质，如P选择素和sCD40L，它们在ACS的发病机制中起作用。虽然已发现阿司匹林（ASA）是治疗ACS的有效药物，但由于其额外的抗血小板和抗炎作用，加用硫酸氢氯吡格雷已被发现可进一步改善临床结局。关于双联抗血小板治疗对ACS患者这些标志物的影响，现有数据较少。

目的

本研究旨在评估在接受ASA治疗的非ST段抬高型ACS患者中给予氯吡格雷的有效性及临床意义。

方法

本随机、单盲、对照试验在希腊雅典希波克拉底医院心内科一部进行。年龄≥21岁的非ST段抬高型ACS住院患者被随机分为2组之一：ASA 325 mg/d，持续1周，随后给予ASA（100 mg/d）加氯吡格雷（300 mg负荷剂量，随后100 mg/d），持续36周（ASA + 氯吡格雷组）或仅给予ASA（325 mg/d，持续1周，随后75 mg/d，持续36周）（ASA组）。在入院时以及治疗的8小时、48小时和6天时测定血清sCD40L、hsCRP和P选择素水平。通过临床随访，采用Kaplan-Meier无重大不良心血管事件（MACE）曲线评估hsCRP（≥3 mg/L）和sCD40L（≥5 μg/L）水平高低不同的患者在52周内发生MACE（包括心血管相关死亡）的发生率。