Association of clopidogrel low response and stent thrombosis

目的 探讨氯吡格雷低反应性与冠状动脉支架内血栓的关系,评估氯吡格雷剂量加倍后的疗效.方法 连续入选9例经冠状动脉造影确诊的支架内血栓患者为观察组,连续入选100例接受支架植入治疗的冠心病患者为对照组.用光学血小板聚集仪检测花生四烯酸(AA)和二磷酸腺苷(ADP)诱导的血小板聚集率(PLAA和PLADP).将PLAA＞20％、PLADP＞40％分别定义为阿司匹林和氯吡格雷低反应性,对观察组氯吡格雷低反应者加倍剂量至150 mg/d,随访PLADP及临床事件.结果 观察组氯吡格雷低反应的发生率高于对照组(100％ vs.27％)(P＜0.01);观察组PLADP水平显著高于对照组[(53.6±6.3)％vs.(31.9±14.0)％](P＜0.01);观察组氯吡格雷剂量加倍后,血小板聚集率显著降低[(53.6±6.3)％ vs.(37.0±10.9)％](P＜0.01).观察组与对照组均未检出阿司匹林低反应患者.结论 氯吡格雷低反应性是冠状动脉支架内血栓形成的危险因素.氯吡格雷剂量加倍可显著降低残余血小板聚集率,可能减少支架内血栓形成事件的发生.     

埃索美拉唑对氯吡格雷高维持量作用的影响

目的评价埃索美拉唑对非ST段抬高急性冠脉综合征(NSTE-ACS)患者支架置入术后应用氯吡格雷效果的影响。方法将102例患者随机均分为对照组和埃索美拉唑组,出院时均给予阿司匹林75 mg和氯吡格雷150 mg长期口服,埃索美拉唑组另给予埃索美拉唑20 mg口服,每日2次。以磷酸化血小板血管扩张剂刺激磷蛋白(VASP)磷酸化程度计算的血小板反应指数(PRI)用于评估氯吡格雷效果和对二磷酸腺苷(ADP)诱导的血小板聚集反应性(ADP-Ag)。结果随访1个月,埃索美拉唑组患者血小板氯吡格雷反应性与对照组有同样的效果,PRI VASP为(37.3±5.8)%对(39.4±6.3)%,P>0.05;血小板聚集反应性埃索美拉唑组与对照组有同样的效果,ADP-Ag为(51.3±14.6)%对(52.7±15.3)%,P>0.05。结论对于接受氯吡格雷治疗且同时需要质子泵抑制剂治疗时,建议应尽可能选择对CYP2C19抑制效力小的埃索美拉唑。     

氯吡格雷与替格瑞洛治疗老年急性冠状动脉综合征患者的临床疗效对比分析

目的探讨氯吡格雷与替格瑞洛治疗老年急性冠状动脉综合征患者的临床疗效。方法将我院收治的188例老年急性冠状动脉综合征患者随机分为对照组94例和观察组94例,对照组采取氯吡格雷联合阿司匹林治疗,观察组采取替格瑞洛联合阿司匹林治疗,比较2组患者的再发心肌梗死、主要终点事件、支架内血栓形成等不良反应发生情况。结果观察组及对照组的再发心肌梗死发生率分别为1.06%(1/94)、5.32%(5/94);主要终点事件发生率分别为2.13%(2/94)、5.32%(5/94);支架内血栓形成发生率分别为1.06%(1/94)、4.25%(4/94);经χ~2检验,观察组的再发心肌梗死、主要终点事件、支架内血栓形成发生率均明显低于对照组,均有P<0.05。结论与氯吡格雷联合阿司匹林相比,采用替格瑞洛联合阿司匹林治疗老年急性冠状动脉综合征患者,可有效减少患者再发心肌梗死、主要终点事件、支架内血栓形成发生率。     

氯吡格雷对冠状内支架置入术后预后的影响

目的 观察冠脉支架置入术后应用氯吡格雷(抗血小板药)加阿司匹林的抗血小板聚集作用及其安伞性.方法 67例经皮冠状动脉内支架置入术治疗冠心病患者,随机分为试验组(36例)和对照组(3l例):对照组,支架置入术后,继续服用阿司匹林和氯吡格雷9～12个月;试验组,此后继续服用阿司匹林和氯吡格雷18～24个月.观察2组主要心血管事件和出血并发症的发生情况.结果 2组患者主要心血管事件的发生率比较,差异有统计学意义(P<0.05);出血并发症的发生率比较,差异无统计学意义(P>0.05).结论 经皮冠状动脉内支架置入术后应用氯吡格雷加阿司匹林,应用时间越长,其主要心血管事件发生越少且出血并发症的发生率并无增加.     

奥美拉唑和泮托拉唑对氯吡格雷高维持量作用的影响比较

目的评价2种质子泵抑制药奥美拉唑和泮托拉唑对非ST段抬高急性冠脉综合征(NSTE ACS)患者支架置入术后氯吡格雷效果的影响。方法 140例接受冠脉支架置入的NSTE ACS患者,随机分为对照组、奥美拉唑组和泮托拉唑组。出院时给予阿司匹林75 mg和氯吡格雷150 mg长期口服。血小板反应指数(PRI)磷酸化血小板血管扩张剂刺激磷蛋白(VASP)用于评估氯吡格雷反应和对二磷酸腺苷(ADP)诱导的血小板聚集反应(ADP-Ag)。结果随访1个月的结果显示,接受泮托拉唑的患者血小板氯吡格雷反应性明显优于接受奥美拉唑的患者,PRI VASP为(36.3±6.1)%对(48.2±2.7)%(P<0.01)。但2组间ADP-Ag无显著差异(P>0.05)。结论泮托拉唑对氯吡格雷抗血小板活性的抑制作用小于奥美拉唑。     

冠状动脉支架术后氯吡格雷抵抗患者抗血小板治疗的效果

目的探讨冠状动脉支架术后氯吡格雷抵抗患者抗血小板治疗的效果。方法对92例实施冠状动脉支架术患者进行分析,其经血栓弹力图检查确诊为氯吡格雷抵抗;随机抛掷硬币将患者分为对照组(n=46)与观察组(n=46);对照组采用氯吡格雷+阿司匹林治疗、观察组采用替格瑞洛+阿司匹林治疗,分析两组的临床效果。结果术后1、3、6、8个月两组患者的血小板聚集率均在下降且观察组术后各阶段的血小板聚集率均低于对照组(P <0.05);观察组的不良事件发生率为4.3%,对照组的不良事件发生率为21.7%(P <0.05)。结论在冠状动脉支架术后氯吡格雷抵抗患者的治疗中采用替格瑞洛来替代氯吡格雷,具有降低血小板聚集率与将心脏不良事件发生率的作用。     

不同维持剂量氯吡格雷对氯吡格雷抵抗急性冠状动脉综合征患者的有效性及安全性研究

目的探讨对于冠状动脉介入治疗的氯吡格雷低反应的急性冠状动脉综合征(ACS)患者,能否通过增加氯吡格雷维持剂量来降低血小板聚集率,改善临床预后,从而为氯吡格雷低反应的ACS患者围手术期药物选择提供依据。方法选择诊断为ACS并行经皮冠状动脉介入治疗(PCI)的氯吡格雷低反应患者208例。随机分为2组,A组(常规剂量组)PCI术前给予600mg氯吡格雷负荷量,术后给予75mg氯吡格雷维持剂量至少1年;B组(双倍剂量组)PCI术前给予600mg氯吡格雷负荷量,术后给予150mg氯吡格雷维持剂量30d,以后继续给予75mg氯吡格雷维持剂量至少1年。1血小板聚集率测定:测定各组患者入院时的基础血小板聚集率及氯吡格雷600mg负荷量用药4h、维持量氯吡格雷用药后7、14、30、90、180d的血小板聚集率。2临床随访:所有患者均在180d内进行随访,观察不同维持剂量组主要心脏不良事件(MACE)事件和出血事件的发生率。结果 12组患者维持量氯吡格雷用药后7d的血小板聚集率差异无统计学意义;14、30、90、180d的血小板聚集率双倍剂量组较常规剂量组显著降低,差异有统计学意义。2随访180d结果显示双倍剂量组较常规剂量组MACE事件发生率有所减少,但是差异无统计学意义;2组出血事件发生率差异也无统计学意义。结论 PCI术后应用150mg氯吡格雷维持剂量与常规氯吡格雷维持剂量相比,可进一步降低氯吡格雷低反应患者的血小板聚集率,但是MACE事件发生率无明显降低,且不增加出血事件的发生率。     

阿司匹林、氯吡格雷、西洛他唑对冠脉支架植入术后患者血小板高反应性的影响

目的探讨阿司匹林、氯吡格雷、西洛他唑对冠脉支架植入术后患者血小板高反应性的影响。方法选取2014年1月~2016年12月在我院接受冠状动脉支架术患者120例为观察对象,将患者按照随机数字表法分为观察组和对照组。对照组患者进行阿司匹林、氯吡格雷联合治疗。观察组患者在对照组的基础上联合西洛他唑进行治疗。比较两组的患者的治疗效果及血小板的活化和聚集指标。于术后6个月对两组患者进行随访,观察并统计两组患者有无临床并发症症状。结果术后第3天,观察组患者MPAR值为(45.32±13.41),对照组患者MPAR值为(51.68±11.62);观察组CD62P值为(10.09±12.32),对照组CD62P值为(13.28±9.37);观察组患者PAC-1值为(57.56±20.23),对照组患者PAC-1值为(63.17±18.60);观察组患者术后1年内发现不良心脑血管事件7例,总体发生率为11.6%,对照组患者术后1年发现不良心脑血管事件19例,总体发生率为31.7%,以上各组数据之间差异均具有统计学意义(P<0.05)。另外观察组患者术后1年内,临床并发症总体发生率于对照组相比,无明显差异。结论阿司匹林、氯吡格雷联合西洛他唑论治疗与传统阿司匹林联合氯吡格雷治疗相比抑制冠脉支架术后血小板活化和聚集效果更为显著,能够明显降低不良心脑血管事件发生率,而临床并发症发生率并未增加。     

氯吡格雷

氯吡格雷(clopidogrel)是一种噻吩并吡啶类化合物,它能不可逆地抑制血小板聚集,其作用机理与阿司匹林和相关药物不同,即不是通过花生四烯酸代谢,而是选择性抑制位于血小板表面的、与腺苷酸环化酶偶联的ADP受体进而抑制纤维蛋白原与血小板的结合,从而阻止了血小板聚集。氯吡格雷的主要作用是抑制血栓形成。家兔试验表明,血管内皮损伤后,该化合物可以减少血小板往血管内皮的粘附,减轻血管内膜的增厚,阿司匹林无此作用。大鼠颈动脉损伤后,氯吡格雷能以剂量依赖方式抑制动脉血栓形成,它还以同样方式减少大鼠静脉内的血栓形成。冠状动脉血栓溶…     

硫酸氢氯吡格雷与替格瑞洛治疗急性冠状动脉综合征患者的临床研究

目的 观察硫酸氢氯吡格雷与替格瑞洛治疗急性冠状动脉综合征的临床疗效及对患者血脂的影响。方法 经皮冠状动脉介入术的急性冠状动脉综合征患者按照抗血小板聚集药物的不同,将其分为氯吡格雷组和替格瑞洛组。氯吡格雷组给予硫酸氢氯吡格雷片75 mg,阿托伐他汀钙片20 mg,阿司匹林肠溶片100 mg,每日1次,口服;替格瑞洛组给予阿托伐他汀钙片20 mg,每日1次,阿司匹林肠溶片100 mg,每日1次,替格瑞洛片90 mg,每日2次,口服。2组均连续治疗1个月。比较2组患者的临床疗效、中性粒细胞/淋巴细胞比(NLR)、低密度脂蛋白胆固醇(LDL-C)、血小板最大聚集率以及药物不良反应发生情况。结果 氯吡格雷组144例和替格瑞洛组145例。替格瑞洛组治疗后总有效率为86.90%,高于氯吡格雷组的75.00%,差异有统计学意义(P<0.05)。治疗后,氯吡格雷组和替格瑞洛组的NLR水平分别为3.26±0.15和3.10±0.11;LDL-C水平分别为(2.24±0.14)和(1.77±0.16)mmol·L^-1,差异有统计学意义(P<0.05)。氯吡格雷组患者在术后2...     

The role of the cytochrome P450 polymorphisms in clopidogrel efficacy and clinical utility

Clopidogrel, an antiplatelet agent, prevents platelet aggregation by inhibiting the adenosine disphosphate (ADP) P2Y12 receptor, which is located on the platelet surface. Although dual antiplatelet therapy appears to be efficient, a considerable number of patients continue to experience adverse cardiovascular events, such as stent thrombosis. The percentage of low response to antiplatelet therapy varies from 4% to 30% of patients depending on the cut-off values. In addition, several factors such as poor absorption, drug-to-drug interactions, inadequate dosing, elevated body mass index, insulin resistance and the nature of acute coronary syndromes have been implicated in low clopidogrel response. Recently, studies have focused on the role of genetic polymorphisms encoding enzymes that participate in clopidogrel hepatic metabolism or receptors involved in intestinal absorption and ADP induced platelet aggregation, which may affect the percentage of platelet inhibition after clopidogrel administration. The management of clopidogrel resistance remains a controversial issue and additional studies are required to evaluate the safety and efficacy of increased loading of clopidogrel or replacement with other new antiplatelet agents such as prasugrel.     

氯吡格雷对阿司匹林抵抗的影响

目的研究氯吡格雷对冠心病患者阿司匹林抵抗的影响。方法筛选出冠心病患者中发生阿司匹林抵抗的患者58例入选本研究,随机分为对照组和氯吡格雷组,分别给予阿司匹林100mg＋安慰剂每天和阿司匹林100mg＋氯吡格雷75mg每天,14天后采用全血电阻法检测血小板聚集功能。结果与对照组相比,氯吡格雷组使ADP（二磷酸腺苷）诱导的血小板聚集功能显著抑制[（1．3±0．48）Ω比（12．8±2．5）Ω],P〈0．01,但对从（花生四烯酸）诱导的血小板聚集没有影响[（12．3±4．3）Ω比（11．9±4．9）Ω],P〉0．05。结论合用氯吡格雷不能完全改善冠心病患者的阿斯匹林抵抗,对这部分患者应加强综合治疗。     

急性冠脉综合征患者氯吡格雷抵抗与近期疗效的临床观察

目的：检测急性冠脉综合征（acute coronary syndrome,ACS）患者服用氯吡格雷治疗前后腺苷二磷酸（adenosine diphosphate,ADP）诱导的血小板聚集率变化,同时观察临床主要心血管事件发生率。方法：测定88名冠心病稳定型心绞痛患者和102名ACS患者服用氯吡格雷前与服用后第5天ADP诱导的血小板聚集率,按照血小板聚集率的抑制程度分为无反应、低反应和正常反应组。同时观察单纯药物治疗和联合支架置入术治疗患者1月内主要心血管事件发生率。结果：服用氯吡格雷前,ACS患者ADP诱导的血小板聚集率明显高于稳定型心绞痛患者[（80．4±7．8）％US（56．2±12．1）％,P〈0．05]。ACS患者服用氯吡格雷的过程中,无反应患者、低反应患者的发生率分别是21．6％、27．4％。结论：ACS患者呈现出血小板高聚集状态。服用氯吡格雷后血小板聚集率的抑制程度呈现明显个体差异。氯吡格雷无反应和低反应患者在治疗过程中,心绞痛发生率明显高于氯吡格雷正常反应患者（P〈0．05）。联合支架置入术患者心绞痛发生率低于单纯药物治疗患者（P〈0．05）。     

The effect of St John's Wort on the pharmacodynamic response of clopidogrel in hyporesponsive volunteers and patients: increased platelet inhibition by enhancement of CYP3A4 metabolic activity

Clopidogrel is metabolically activated by cytochrome P450 (CYP) isoenzymes. We evaluated whether St. John's wort (SJW), a CYP2C19 and CYP3A4 inducer, enhances the pharmacodynamic response of clopidogrel. Volunteers (n = 45) were screened for clopidogrel hyporesponsiveness after a 300-mg load. After a 7-day washout, hyporesponders (n = 10) received 14 days of SJW (300 mg 3 times a day) followed by a second 300-mg clopidogrel. Platelet aggregation was measured at 0, 2, 4, and 6 hours postloading; hepatic CYP3A4 activity was simultaneously determined at 0 and 4 hours by the erythromycin breath test. A prospective, randomized, double-blind pilot study was conducted in postcoronary stent patients (n = 85) on clopidogrel 75 mg/d screened for clopidogrel hyporesponsiveness. Hyporesponders (n = 20) were randomized to SJW (n = 10) or placebo (n = 10); platelet aggregation was measured before and after 14 days of therapy. In volunteers, SJW decreased platelet aggregation (59% ± 14% vs. 40% ± 15% at 2 hours, P = 0.02; 56% ± 10% vs. 44% ± 13% at 4 hours, P < 0.03; and 55% ± 14% vs. 37% ± 14% at 6 hours, P = 0.01) and increased CYP3A4 activity (2.1% ± 0.4% CO2 exhaled per hour before vs. 2.9% ± 0.6% CO2 exhaled per hour after SJW, P = 0.002). In patients, SJW decreased platelet reactivity (226 ± 39 vs. 185 ± 49 P2Y12 reactivity units, P = 0.0002) and increased platelet inhibition (23% ± 11% vs. 41% ± 16%, P = 0.002). SJW may be a future therapeutic option to increase CYP metabolic activity and antiplatelet effect of clopidogrel in hyporesponders.     

氯吡格雷抵抗与直接经皮冠状动脉介入术中无复流的关系研究

目的观察氯吡格雷抵抗与急性心肌梗死（AMI）患者直接经皮冠状动脉介入（PPCI）术中无复流的关系。方法人选2009年1月至2010年12月因AMI住院行PPCI术患者共765例,所有患者术后5d晨起空腹采血,根据对二磷酸腺苷诱导的血小板聚集抑制率判定是否出现氯吡格雷抵抗。根据术中是否出现无复流分为无复流组（81例）和对照组（684例）,比较2组临床特点,分析氯吡格雷抵抗与术中出现无复流的关系。结果2组男性比、高血压患病率、吸烟情况、发病至就诊时间、白细胞计数、血小板计数、梗死相关动脉、支架直径、门-球时间差异无统计学意义（P〉0．05）。与对照组比较,无复流组糖尿病患病率[（29．6％（24／81）比19．9％（136／684）,P=0．044]、年龄[（62±10）岁比（60±11）岁,P=0．032]、氯吡格雷抵抗发生率[38．3％（31／81）比24．9％（170／684）,P=0．011]、术前心肌梗死溶栓试验血流0级[82．7％（67／81）比70．5％（482／684）,P=0．026]、应用替罗非班者占比[42．0％（34／81）比30．8％（211／684）,P=0．045]、肌钙蛋白I（cTnI）峰值[（58±14）μg/L比（54±13）μg/L,P=0．015]、肌酸激酶同工酶（CK—MB）峰值[（156±42）U／L比（145±40）U／L,P=0．027]、肌酸激酶（CK）峰值（1437±202）U／L比（1388±216）u／L,P=0．041]、病死率[4．9％（4／81）比1．0％（7／684）,P=0．022]明显升高,ST段回落率[66．7％（54／81）比82．5％（564／684）,P=0．001]及左心室射血分数（LVEF）[（48±11）％比（51±11）％,P=0．028]则明显下降。Logistic回归分析结果显示,在校正了其他危险因素之后,氯吡格雷抵抗是PPCI术中出现无复流的独立影响因素（比值比=3．466,95％置信区间：1．447—10．876,P=0．019）。结论氯吡格雷抵抗是PPCI术中出现无复流的可能机制之一,严重影响预后。     

Interindividual variability in the laboratory response to the aspirin-clopidogrel combination: are patients with stent occlusion "resistant" to treatment?

Interindividual variability of biological response to antiplatelet agents is an opened question, which constitute the purpose of recent publications. Indeed, a wide interindividual variability in the laboratory response to antiplatelet agents such as aspirin and/or clopidogrel has been shown. However, only few clinical data are available to demonstrate the relationship between a poor laboratory response to antiplatelet treatment and the occurrence of stent thrombosis. The aim of this study is to compare photometric platelet aggregation profiles of two groups of patients who had undergone percutaneous coronary intervention with stent implantation (one group with at least one subacute thrombotic event following stent implantation and one historical control group free of thrombotic events) to determine whether there is a parameter which could be useful in identifying patients with a risk of having a thrombotic event related to poor response to antiplatelet treatment. We found some differences between the two groups regarding the maximal light transmission after stimulation with arachidonic acid (1,39 mM) or collagen at low concentration (Horm, 2 microg/mL) but not after stimulation with ADP irrespective of the concentration studied (10, 5 and 2,5 microM). However, platelet inhibition response to ADP could be assessed with another parameter, the disaggregation percentage, which was significantly lower in patients with than without thrombosis, and may be used as marker to distinguish patients with a higher risk of thrombosis.     

Clopidogrel resistance is associated with long-term thrombotic events in patients implanted with drug-eluting stents

Background: There are limited prospective data on clopidogrel resistance and clinical outcome of patients with selective coronary drug-eluting stent (DES) implantation.Objective: To investigate whether clopidogrel resistance is associated with longterm thrombotic events in patients with selective coronary DES implantation.Methods: A total of 154 patients who underwent selective percutaneous coronary intervention (PCI) with DES were enrolled in this study. Platelet aggregation was measured using light transmittance aggregometry (LTA) before clopidogrel administration (baseline) and 24 hours after loading with clopidogrel 300 mg. Clopidogrel resistance was defined as ≤10% absolute difference between baseline aggregation and post-administration aggregation. All patients who received the same anti-platelet treatment were followed up for 1 year after discharge for the incidence of a composite endpoint consisting of cardiovascular death, myocardial infarction (MI) and revascularization, and secondly for the incidence of stent thrombosis.Results: The incidence of clopidogrel resistance is 20.28% in our study population. Patients who are complicated by diabetes mellitus, smoke, or have a higher body mass index (BMI) tend to have clopidogrel resistance. Patients in the clopidogrel-resistant group have significantly higher incidences of composite endpoints (21.88% vs 4.92%; p = 0.006) and stent thrombosis (12.5% vs 1.64%; p= 0.017) than patients in the clopidogrel-response group during 1-year follow-up.Conclusions: Diabetes, smoking, and high BMI are associated with clopidogrel resistance, and clopidogrel resistance indicates an increased risk of long-term thrombotic events in patients implanted with DES.     

Light transmittance aggregometry induced by different concentrations of adenosine diphosphate to monitor clopidogrel therapy: a methodological study

Light transmission aggregation (LTA) is considered the reference method to identify residual platelet reactivity (RPR) in high-risk patients with coronary artery disease on clopidogrel treatment. An international standardization of this technique is still ongoing and different concentrations of adenosine diphosphate (ADP) as the agonist for LTA have been used to evaluate the inhibitory effect of clopidogrel treatment. To evaluate RPR, LTA was performed using different ADP concentrations (2, 5, 10, and 20 μmol/L) in 466 high-risk patients with coronary artery disease on dual antiplatelet therapy who underwent percutaneous coronary intervention and in 46 healthy subjects. A VerifyNow P2Y12 assay was assessed as a point-of care system. Imprecision studies showed higher coefficients of variation for LTA by 2 and 5 μmol/L ADP (healthy subjects: 4.7% and 3.9%; patients: 6.8% and 5.2%, respectively) in comparison with those obtained determining LTA using 10 and 20 μmol/L ADP (healthy subjects: 2.2% and 2.3%; patients: 2.7% and 3.1%, respectively). In patients, a significant difference (P < 0.0001) between mean values of LTA obtained with all ADP concentrations was found, even if LTA data were significantly correlated (at least: rho = 0.88, P < 0.0001). However, data from 10 and 20 μmol/L ADP LTA were very similar and highly concordant (k = 95.9%). All agreements were significant (for all P < 0.0001), in particular the agreement between 10 and 20 μmol/L ADP LTA was very good (k = 0.86, P < 0.0001). A moderate agreement between VerifyNow and both 10 and 20 μmol/L ADP LTA was observed. LTA by 10 and 20 μmol/L ADP gave equivalent percentages of aggregation and highly concordant results in terms of RPR in patients with coronary artery disease on clopidogrel. Significant concordant results were observed between both 10 and 20 μM ADP LTA and VerifyNow. This suggests that a concentration of 10 μmol/L ADP may be considered adequate for the identification of RPR of patients on clopidogrel and should be preferred for standardization LTA.     

氯吡格雷对二磷酸腺苷诱导的血小板聚集的影响

目的 :探讨氯吡格雷对血小板聚集率的影响。方法 :血小板聚集率增高病人 2 4例 ,男性 1 4例 ,女性 1 0例 ,年龄 (5 9±s 1 0 )a。给予氯吡格雷5 0mg ,po,qd×4wk。在服药后 8d,4wk后用光学法测定血小板聚集率 (ADP诱导法 ) ,Duke法测定出、凝血时间 ,凝血因子Ⅰ及血小板计数。结果 :高血小板聚集率的病人使用氯吡格雷后血小板聚集率明显下降 ,治疗后 8d,4wk分别下降 (3 1±2 5 ) % ,(3 2± 2 1 ) % ,(P <0 .0 1 )。但出、凝血时间 ,血小板计数及凝血因子Ⅰ含量在使用氯吡格雷后无明显变化。结论 :氯吡格雷可有效拮抗ADP诱导的血小板聚集作用     

ADP Receptor Antagonism

ADP is one of the most important mediators of both physiologic hemostasis and thrombosis. Development and utilization of agents that block ADP receptors on the platelet membrane, namely thienopyridines, has represented a major advancement for treatment of patients undergoing percutaneous coronary interventions and those with acute coronary syndromes. Currently, clopidogrel, a second-generation thienopyridine that inhibits the ADP P2Y(12) receptor, represents the treatment of choice, in addition to aspirin, for the prevention of stent thrombosis. Further, long-term adjunctive use of this ADP P2Y(12) receptor antagonist is also associated with improved clinical outcomes in high-risk patients, and represents the standard of care for these patients. Despite the unambiguous clinical benefit associated with clopidogrel, accumulating experience with this drug has also led to identification of some of its drawbacks, which are related to inadequate platelet inhibition with standard dosage regimens as well as to its irreversible antiplatelet effects. This has led to the questioning of currently recommended clopidogrel dosage regimens as well as to the development of novel and more potent ADP P2Y(12) receptor antagonists, some of which are also reversible agents. Numerous studies are currently ongoing with the objective of demonstrating how more potent platelet inhibition using higher loading and maintenance dose regimens of clopidogrel or novel ADP P2Y(12) receptor antagonists - such as prasugrel, ticagrelor (AZD 6140) and cangrelor - will affect clinical outcomes. This article reviews the current knowledge of platelet ADP P2Y(12) receptor antagonism and the projected developments in this field.