不同质子泵抑制剂对氯吡格雷抗血小板效应影响研究的进展

质子泵抑制剂（PPIs）常被用来预防氯吡格雷与阿司匹林的双联抗血小板治疗引起的消化道出血不良反应,但近年来陆续有研究表明,PPIs可能会拮抗氯吡格雷的抗血小板作用,同时增加主要不良心血管事件（MACE）的发生率;可是也有相反报道,认为它不会增加MACE及死亡率。本文就此争议做一综述。     

氯吡格雷和阿司匹林合用与单用阿司匹林治疗心力衰竭引起血小板聚集的结果

充血性心力衰竭 (CHF)是西方国家最常见死因之一 ,血栓是CHF常见并发症 ,严重CHF病人每年中风危险率以 4%的速度增长 ,氯吡格雷 (clopidogrel)是一种新的血小板二磷酸腺苷(ADP)受体拮抗剂 ,能减少中风、心肌缺血、心血管死亡发病率 ,对CHF病人 ,ADP受体拮抗剂是否抑制血小板功能不很清楚 ,本文对CHF伴血小板活性增强病人合用氯吡格雷和阿司匹林与单用阿司匹林的抗血小板特性进行了评估。研究对象为美国Baltimore城 88名心血管门诊CHF病人 ,所有病人左室射血分数 <40 %或收缩性CHF ,纽约心脏功能分级Ⅱ Ⅳ级 ,病人血小板活性增…     

抗血小板药抵抗与卒中防治

大量研究证实,抗血小板药能使卒中、心肌梗死或死亡的相对危险度平均降低22％.然而,许多患者在服用抗血小板药期间仍出现血栓形成事件,这被称为“抗血小板药抵抗”.其发生率各家报道差异很大,阿司匹林抵抗的发生率为3％～85％,氯吡格雷抵抗的发生率为28％～44％.抗血小板药抵抗的确切原因尚不清楚,可能与药物生物利用度下降、基因多态性、其他血小板激活通路被激活、循环血小板增加等多种因素有关.目前,已有多种实验室检查方法被用于抗血小板药抵抗的检测,其标准各不相同.此外,抗血小板药抵抗的应对措施亦无定论,给卒中防治带来更大的困难.     

不同剂量氯吡格雷抑制血小板聚集功能时效探讨

目的 探讨氯吡格雷常用剂量下，血小板聚集率的变化规律及其临床意义。方法 40例经体检健康的志愿者，随机分为4组，每组10例，第一组一次服用75mg氯吡格雷；第二组服用氯吡格雷75mg／d，连服3天停药；第三组服用氯吡格雷75mg／d连服7天停药；第四组一次服用300mg氯吡格雷。各组分别在不同时间点进行采样，样本用二磷酸腺苷（ADP）进行血小板聚集实验。结果 第一组在停药后6天血小板聚集率恢复到服药前水平。第二组血小板聚集率在服药的3天、停药后的1天、2天与用药前差异有非常显著性（P〈0．01），第10天后恢复到服药前水平。第三组停药后4天内血小板聚集率受非常明显抑制（P〈0．01），6天内受明显抑制（P＜0．05）。第四组服药后2h即可观察到药物对血小板聚集率的非常明显的抑制作用（P〈0．01），停药4天后血小板聚集率恢复到服药前水平。结论 首服剂量越大，维持服药的时间越长，血小板聚集功能恢复所需时间越长。     

药物支架术后低剂量氯吡格雷抗血小板方案的安全性研究

目的比较冠心病患者在置入药物洗脱支架（DES）后服用50 mg氯吡格雷和75 mg氯吡格雷加阿司匹林的双重抗血小板方案的疗效和安全性。方法连续入选2005年6月到2006年12月间在我院初次行经皮冠状动脉介入治疗确定为冠状动脉简单病变并置入1～2枚药物洗脱支架的冠心病患者294例。将符合入选标准的患者随机分成强化管理条件下75 mg组（75IM）和50 mg组（50IM）和一般管理条件下75 mg组（75NM）三组。对于强化管理组的患者通过出院时发放教育材料,电话预约,邮件提醒等强化措施提高患者依从性。三组患者通过门诊或电话随访1年,比较组间死亡、非致死性心肌梗死、支架内血栓、靶血管重建、脑卒中和任何缺血原因的再入院率,以及出血、胃肠道不良反应等药物安全性的差异。结果两组患者基线水平特征无明显差异。75IM组和50IM组6个月及1年期死亡、非致死性心肌梗死、紧急靶血管重建、脑卒中联合终点的发生率差异均无统计学意义;1年期次要联合终点（MACE、脑卒中、任何原因的再血管化及任何缺血原因的再入院）50IM组和75NM组间差异也无统计学意义（OR=0.47,95%CI0.21～1.09,P=0.069）。结论冠状动脉简单病变患者置入DES术后,使用氯吡格雷50mg维持剂量与75mg标降维持剂量相比较,1年期缺血不良事件发生率差异无统计学意义。     

不同氯吡格雷代谢型急性心肌梗死患者的血小板聚集率变化

目的观察不同氯吡格雷代谢型急性心肌梗死患者使用氯吡格雷后血小板聚集功能的被抑制情况。方法入选2013年3—8月急性心肌梗死患者48例,经过基因检测分为氯吡格雷慢代谢型6例、快代谢型17例和中间代谢型25例。患者均于入病房前服用负荷剂量阿司匹林300 mg和氯吡格雷300 mg,之后阿司匹林100 mg/d和氯吡格雷75 mg/d连续服用,于服药后第6天检测血小板聚集率、血细胞计数、纤维蛋白原含量和肝肾功能。结果所有患者服用氯吡格雷后第6天的血小板聚集率明显下降,二磷酸腺苷、肾上腺素诱导的抑制率分别为74%和84%。氯吡格雷快代谢型、中间代谢型和慢代谢型3组急性心肌梗死患者的二磷酸腺苷诱导的血小板聚集率分别为22.2%±13.4%、32.1%±20.1%和18.6%±13.9%(P>0.05),3组血小板抑制率分别为87%、78%和82%。结论本研究中不同氯吡格雷代谢型急性心肌梗死患者的血小板聚集功能的抑制情况无明显差异。     

不同种类质子泵抑制剂对氯吡格雷抗血小板疗效的影响

氯吡格雷作为一种新型的抗血小板药,已与阿司匹林联合广泛应用于临床,成为冠心病抗血小板药物治疗的基石。双联抗血小板治疗使胃肠道并发症的出现增多,故临床上常规加用质子泵抑制剂,以预防双联抗血小板治疗引发的胃肠道并发症。但国外最新研究发现质子泵抑制剂会影响氯吡格雷的疗效,降低其抗血小板的活性,使临床心血管不良事件发生率增加。     

质子泵抑制剂对PCI术后氯吡格雷抗血小板作用的影响

目的 探讨经皮冠状动脉介入术(PCI)后抗血小板治疗中应用质子泵抑制剂(PPI)对氯吡格雷抗血小板作用的影响.方法 选择PCI术后患者336例,术后立即服用氯吡格雷600 mg及阿司匹林500 mg,随后应用氯吡格雷75 mg/d、阿司匹林100 mg/d.术后同时服用PPI类药物以预防消化道出血的患者148例(观察组),其中122例给予口服泮托拉唑,14例给予口服奥美拉唑,12例给予口服埃索美拉唑.没有服用PPI类药物的188例患者作为对照组.在服用氯吡格雷48 h后检测两组血小板聚集率,以氯吡格雷抵抗(CLR)评价抗血小板聚集效果.比较不同PPI药物与CLR的相关性.结果 两组血小板阻抗变化差异无统计学意义(P均＞0.05).两组CLR发生率差异无统计学意义(P＞0.05).奥美拉唑、埃索美拉唑对CLR影响较大.结论 接受氯吡格雷+阿斯匹林双重抗血小板治疗的患者服用PPI标准剂量时,短期内不影响氯吡格雷的抗血小板作用.     

血栓弹力图评价抗血小板治疗的疗效及相关因素分析

目的用血栓弹力图(TEG)的方法评价抗血小板治疗的疗效和相关因素分析。方法选择自愿完成TEG测定的年龄≥60岁军队老年男性955例,按服用抗血小板药物分4组,阿司匹林组368例,氯吡格雷组115例,双联抗血小板药物组(双抗组)43例,无抗血小板药物组429例。用TEG指标评价抗血小板药物的有效性,并用多因素logistics回归分析影响疗效的相关因素。结果阿司匹林组花生四烯酸(AA)途径血小板抑制率(AA抑制率)为(48.0±19.3)%,氯吡格雷组二磷酸腺苷(ADP)途径血小板抑制率(ADP抑制率)为(63.0±18.2)%,双抗组AA抑制率为(51.0±16.5)%,ADP抑制率为(46.0±15.3)%,均在起效范围内。AA途径中,阿司匹林组与双抗组有效率无差异(45.80%vs 51.16%,P0.05),ADP途径中,氯吡格雷组与双抗组有效率无差异(76.52%vs67.44%,P0.05)。多因素logistics分析示,白细胞计数(OR=0.891,P=0.001),肾小球滤过率(OR=1.016,P=0.013)是增加出血的危险因素;血小板计数(OR=1.026,P=0.000),糖化血红蛋白(OR=1.358,P=0.011)是血栓风险增加的危险因素。结论严格质量控制的TEG测定可以作为临床抗血小板治疗疗效的评估手段之一。     

经皮冠状动脉介入术后双联抗血小板治疗2a临床评价

目的评价经皮冠状动脉介入治疗（P-PCI）术后应用阿司匹林和氯吡格雷双联抗血小板治疗2 a的临床疗效及安全性。方法将128例行P-PCI的急性ST段抬高心肌梗死患者分为两组。A组术后应用阿司匹林和氯吡格雷2 a;B组应用阿司匹林和氯吡格雷1 a,以后均长期应用阿司匹林。评估两组间主要心脏不良事件及安全性指标。结果 A组2例（3.1%）发生主要心脏不良事件与B组6例（9.5%）比较差异有统计学意义（P〈0.05）;两组安全性指标比较差异无统计学意义。结论急性ST段抬高心肌梗死患者P-PCI术后应用双联抗血小板治疗2 a可获得更好的临床效果。     

血栓弹力图法和光密度比浊法对双联抗血小板治疗患者的血小板聚集率检测的比较

目的分析血栓弹力图法（TEG法）和光密度比浊法（LTA法）对经双联抗血小板治疗的急性冠脉综合征（ACS）患者的血小板聚集率检测的相关性。方法募集2010年9月至2012年9月,在解放军总医院住院期间行氯吡格雷和阿司匹林双联抗血小板治疗的ACS患者共93名。在患者经口服双联抗血小板药物稳定剂量后取血,分别采用LTA法和TEG法,检测腺苷二磷酸（ADP）和花生四烯酸（AA）诱导的血小板聚集率,并对不同方法的检测指标进行相关回归分析。结果在93名ACS受试者中,应用LTA法和TEG法检测的ADP诱导的血小板聚集率分别为（59.3±21．34）％和（63．67±28．15）％,两者之间的相关系数为0．814（P〈0．0001）,回归方程为^Y（燃）=0．2＋0．617血栓弹力图法oLTA法和TGA法检测的AA诱导的血小板聚集率分别为（40．87±35．16）％和（46．02±39．26）％,两者的相关系数为0．965（P〈0．0001）,回归方程为“Y（＆{虫{击）=1．077Xm＆#女目＊＋O．02。结论在双联抗血小板治疗的ACS患者中,采用TEG法和u．A法检测的血小板功能具有较好的一致性。     

脑微出血部位和负荷与脑梗死抗血小板治疗的相关分析

目的探讨脑微出血(CMB)发生部位和负荷对脑梗死抗血小板治疗风险及获益的影响。方法选择伴CMB的急性脑梗死患者214例,根据CMB发生部位分为单纯脑叶组39例,深部/幕下组62例,混合部位组113例,随访各组新发脑梗死、脑出血情况,并比较各组治疗前及治疗1年后CMB的变化。结果深部/幕下组既往脑梗死、高血压和糖尿病比例明显高于单纯脑叶组和混合部位组(P<0.05)。混合部位组基线CMB数高于单纯脑叶组和深部/幕下组[(8.69±2.75)个vs(6.65±2.47)个、(6.58±3.17)个,P<0.05]。单纯脑叶组脑出血比例明显高于深部/幕下组和混合部位组(12.8%vs 3.2%、2.7%,P<0.05),且发生脑出血患者中4例基线CMB数>5个。深部/幕下组再发脑梗死比例明显高于单纯脑叶组和混合部位组(24.2%vs 7.7%、9.7%,P<0.05)。3组治疗1年后仅部分患者复查头颅MRI,其中单纯脑叶组28例,深部/幕下组40例,混合部位组56例。单纯脑叶组CMB进展比例明显高于深部/幕下组和混合部位组,差异有统计学意义(35.7%vs 12.5%、10.7%,P<0.05),且病灶以脑叶为主。结论抗血小板治疗风险与CMB部位和负荷相关,单纯脑叶CMB抗血小板治疗的脑出血风险增加,治疗后CMB更易进展。深部/幕下CMB患者脑梗死复发风险更高。     

高龄老年应用氯吡格雷与阿司匹林抗血小板治疗的临床研究

目的对比研究高龄老年应用氯吡格雷与阿司匹林抗血小板治疗的效果及安全性。方法91例高龄老年冠心病患者随机分为氯吡格雷组(50 mg/d)、阿司匹林组(100 mg/d)及对照组(复方丹参滴丸10粒3次/d),药物治疗8周后,观察实验前后血小板聚集率改变、胃黏膜出血、对中性粒细胞及血小板的影响以及凝血三项的改变。结果与对照组比较,氯吡格雷组与阿司匹林组对血小板聚集率均有确切的抑制作用;在血小板聚集率抑制方面,氯吡格雷组优于阿司匹林组;各组实验前后均未出现中性粒细胞及血小板的显著变化;在胃黏膜损伤方面,虽然阿司匹林组发生例数较多,但各组均无显著差异;阿司匹林组及对照组实验前后凝血指标未发生变化,氯吡格雷组用药后活化部分凝血酶时间延长,与对照组比较有显著差异,而用药前两组无显著差异。结论高龄老年应用氯吡格雷与阿司匹林均能获得确切的抗血小板聚集效果,且较安全,其中氯吡格雷效果优于阿司匹林。     

The use of the VerifyNow system to monitor antiplatelet therapy: A review of the current evidence

Multiple studies have demonstrated the effectiveness of dual or triple antiplatelet therapy with aspirin, clopidogrel and glycoprotein (GP) IIb/IIIa therapy in patients with acute coronary syndromes as well as in patients undergoing coronary stent implantation. In the last few years, it is becoming clear that not all patients receive the full benefits with the current standard dosages of antiplatelet therapy. Specifically, numerous studies have revealed a wide interindividual variability in the response to these antiplatelet agents and, more importantly, both nonresponsiveness as well as a heightened residual platelet reactivity have been linked to the occurrence of adverse cardiovascular events. Therefore, assays that identify those patients with an impaired responsiveness or a heightened platelet reactivity despite dual antiplatelet therapy may contribute to better risk stratification and will probably improve clinical outcome when appropriate action is initiated. Likewise, a considerable number of patients do not achieve the minimal inhibition of aggregation threshold with the current recommended weight-adjusted dosages of GP IIb/IIIa therapy. Identifying and optimizing the absolute degree of platelet inhibition in this subgroup of patients will probably improve clinical outcome. The VerifyNow platform is one of the most user friendly point-of-care platelet function test systems because it produces rapid results at the patient bedside. The purpose of the present paper is to give insight into the principal mechanisms of the VerifyNow system, to discuss its clinical utility for the monitoring of antiplatelet therapy and to discuss the proposed cut-off levels to segregate responders from non-responders for the different types of antiplatelet therapy.     

PCI术后双联抗血小板药物治疗的最佳维持剂量

经皮冠脉介入手术（PCI）已成为解除冠脉血管严重狭窄的主要非外科治疗方法,术后双联抗血小板药物的治疗可有效地预防各种血栓性并发症,减低心血管事件的发生及死亡率。近年来,在PCI后,阿司匹林及氯吡格雷的最佳维持剂量方面存在很多争议,本文就此问题结合大量国内外的研究及指南推荐进行综述,并对新型抗血小板药物的应用前景进行展望。     

Switching antiplatelet regimens: Alternatives to clopidogrel in patients with acute coronary syndrome undergoing PCI: A review of the literature and practical considerations for the interventional cardiologist

Dual antiplatelet therapy with aspirin plus a P2Y₁₂ receptor inhibitor is the cornerstone of treatment for patients with acute coronary syndrome and in those undergoing percutaneous coronary intervention. Clopidogrel is the most widely used P2Y₁₂ receptor inhibitor. Despite the clinical benefits associated with adjunctive clopidogrel therapy, a considerable number of patients continue to experience recurrent cardiovascular events. Importantly, the interindividual response to clopidogrel is variable and is affected by multiple factors, including genetic polymorphisms and drugs that interfere with the conversion of clopidogrel to its active metabolite. The individual variability to clopidogrel‐induced antiplatelet effects has significant clinical implications that can result in an increased risk of atherothrombotic recurrences, including stent thrombosis. The introduction of novel P2Y₁₂ receptor inhibitors, such as prasugrel or ticagrelor, characterized by more potent and consistent platelet inhibitory effects, represents an opportunity for clinicians to consider these alternative therapies to overcome the limitations of clopidogrel. Understanding the strategies and implications of switching antiplatelet treatment regimens is, therefore, key in the clinical setting. This article provides an overview of the literature on switching antiplatelet treatment strategies and practical considerations for the interventional cardiologist. © 2012 Wiley Periodicals, Inc.     

Oral antiplatelet therapy for percutaneous coronary revascularization.

Great strides in interventional pharmacotherapy have been made over the past few decades, virtually all focused on optimizing peri-PCI antithrombotic therapy in order to reduce thrombotic complications. Our understanding of the role of platelets and of antiplatelet therapies in this process continues to evolve. Today, dual or even triple antiplatelet therapy has become standard of care at the time of PCI followed by dual therapy long-term in the majority of patients. However, currently available oral regimens are hampered by limitations including the need to initiate treatment at least a few hours before the procedure to achieve maximum benefit and the safety issues surrounding irreversible platelet inhibition in the uncommon, but not rare situations when a patient requires surgical revascularization. These limitations have led to the suboptimal "real-world" utilization of these proven agents and have fostered the development of a wide variety of alternative platelet inhibitors with theoretical, but still unproven clinical benefits. There are ample clinical data that strongly support the use of aspirin and clopidogrel in virtually all patients undergoing a PCI today. This review will highlight these data as well as emphasize the gaps in our understanding. (c) 2007 Wiley-Liss, Inc.     

Ticagrelor: a novel reversible oral antiplatelet agent

The complex mechanism of platelet activation creates an optimal target for pharmacological treatment in patients with acute coronary syndromes. Current antiplatelet medications that are used in addition to aspirin include the thienopyridines, clopidogrel and prasugrel, but there are several limitations to the use of these medications. Clopidogrel and prasugrel irreversibly bind to the P2Y12 receptor, creating a prolonged antiplatelet effect which can be undesirable when surgery is needed. Clopidogrel requires hepatic activation and produces variable platelet inhibition based on genetic polymorphisms. Prasugrel has more consistent platelet inhibition than clopidogrel but carries with it an increased risk of serious bleeds. Ticagrelor is a drug in a new chemical class that reversibly binds the P2Y12 receptor and noncompetitively blocks adenosine diphosphate-induced platelet activation. It was specifically designed to address the limitations of the available antiplatelet agents while maintaining comparable or better antiplatelet effects. It does not require metabolic activation and demonstrates greater platelet inhibition, a faster offset of action and comparable bleeding risk compared to clopidogrel. The pivotal PLATO (The Study of Platelet Inhibition and Patient Outcomes) trial in patients with an acute coronary syndrome demonstrated improved cardiovascular outcomes, including a reduction in myocardial infarctions and vascular events using ticagrelor as compared to clopidogrel with comparable rates of major bleeds. A puzzling finding from that trial was the lack of benefit with ticagrelor in patients enrolled from the United States, which has led to ticagrelor not being approved at this time in this country. The main adverse events with ticagrelor are bleeding and dyspnea, the latter of which is of unclear etiology and of unknown long-term clinical concern. In summary, ticagrelor is an exciting new oral antiplatelet drug that seems to be more efficacious than clopidogrel, with comparable safety. Whether issues of geographic disparities in response and the unusual side effect of dyspnea ultimately prove problematic has yet to be determined. Nonetheless, ticagrelor is a drug that has the potential to change the standard of care of patients with acute coronary syndromes.