抗血小板新药替卡格雷取代氯吡格雷的探讨

近年来,美国食品药品监督管理局（FDA）已经批准口服抗血小板药物替卡格雷配合使用低剂量阿司匹林,以降低急性冠脉综合征（ACS）血栓性心血管事件的发生率,替卡格雷将是氯吡格雷有力的竞争对手。虽然替卡格雷比氯吡格雷药效更好,但其存在用药依从性问题。另外,替卡格雷联合阿司匹林使用的剂量具有一个黑框警告,并且替卡格雷成本比氯吡格雷高得多。本文就两者的药物特征及临床治疗特点做进一步的阐述,分析成因。     

“抗血小板药临床应用新进展研讨会”会议纪要

血栓的形成是由血管组织损伤、血小板聚集、凝血酶活化所共同作用的结果。其中,血小板异常聚集是导致动脉血栓事件和急性冠状动脉综合征（ACS）的始动因素和罪魁祸首,因而抗血小板治疗成为防治ACS的关键。作为对抗血小板靶位之一的二磷酸腺苷P2Y12受体阻断剂经历了三代药物的更替,替格瑞洛以其作用独特且可逆、起效快、活性强、不经肝酶CYP2C19代谢、所致出血等不良反应小,在多中心、大样本的PLATO研究中显示,治疗后获益明显优于氯吡格雷,ACS者不管接受何种治疗策略的替卡格雷均有广泛获益。成为ACS防治的新军,为临床抗血小板治疗提供更为宽阔的抉择。     

氯吡格雷治疗非ST段抬高型急性冠状动脉综合征的疗效观察

急性冠状动脉综合征（ACS）是心内科的急症,包括ST段抬高的ACS[大部分进展为ST段抬高的心肌梗死（STEMl）]和非ST段抬高的ACS,后者包括不稳定型心绞痛（UA）和非ST段抬高型心肌梗死（NSTEMl）。对于非ST段持续抬高的ACS的强化内科药物中,抗血小板治疗起到至关重要的作用。本研究旨在探讨在低分子肝素和阿司匹林标准治疗的基础上加用新型抗血小板药物氯吡格雷治疗ACS的疗效与安全性。     

国内使用氯吡格雷与替格瑞洛治疗急性冠脉综合征的疗效及安全性分析

目的：分析比较氯吡格雷与替格瑞洛治疗急性冠脉综合征（ACS）的临床有效性以及安全性差别,为ACS抗血小板药物的选择提供合理参考。方法：计算机检索中国知网,万方以及维普三个中文数据库,获得国内公开发表的相关文献,统计分析各篇文献的有效性评测指标、疗效差别、不良反应以及不良事件发生情况等数据,比较氯吡格雷与替格瑞洛治疗ACS的有效性与安全性。结果：共纳入52篇有效文献,涉及病例7 839例。有效性方面,更多的证据提示替格瑞洛临床疗效优于氯吡格雷。主要不良心血管事件（MACE）方面,替格瑞洛组比氯吡格雷组MACE发生更少。2组出血事件发生率无统计学差异,在导致轻度呼吸困难方面替格瑞洛表现不及氯吡格雷。结论：在常规治疗基础上,替格瑞洛比氯吡格雷治疗ACS效果更为明显。除轻度呼吸困难外,安全性不劣势于氯吡格雷,临床可以考虑推广使用。     

双联抗血小板治疗急性冠脉综合征临床研究

目的探讨双联抗血小板（阿司匹林＋氯吡格雷）在治疗急性冠脉综合征（ACS）中的应用价值。方法ACS患者65例,随机分为2组,其中双联抗血小板治疗组（阿司匹林＋氯吡格雷,简称治疗组）32例,单药抗血小板对照组（阿司匹林,简称对照组）33例,治疗后24周为观察终点,观察住院期间心脏事件及严重事件。结果与单药抗血小板比较,双联抗血小板患者预后更佳。结论双联抗血小板治疗需贯穿ACS治疗始终,有助改善患者预后。     

替格瑞洛导致呼吸困难的1例分析

替格瑞洛为新型的抗血小板药物,具有起效快速和作用可逆的特点,ACS（AcuteCoronarySyndromes）患者不论接受PCI术后或仅接受替格瑞洛保守治疗,与氯吡格雷相比,均可显著降低心血管事件,且未见出血风险增加。但该药可使部分ACS患者出现呼吸困难与心动过缓,在临床上应引起重视。本文就1例替格瑞洛导致ACS患者呼吸困难的病例进行分析．并提出临床药师的体会和建议。     

急性冠状动脉综合征患者PCI术后抗血小板治疗的药物经济学评价

摘要：目的:从医疗服务角度,对急性冠状动脉综合征(ACS)患者行经皮冠状动脉介入治疗(PCI)术后两种抗血小板药物治疗方案进行经济学评价。方法:两种治疗方案为在使用阿司匹林基础上,经验性给予国产氯吡格雷,或经验性给予替格瑞洛,由此建立决策树及Markov模型并进行成本-效果分析,评价中国ACS患者PCI术后使用氯吡格雷和替格瑞洛的成本-效果。结果:经验性给予国产氯吡格雷联合阿司匹林治疗方案为成本最低方案,但直接给予替格瑞洛联合阿司匹林治疗方案具有较好的成本-效果。结论:对于PCI术后的ACS患者抗血小板治疗,最推荐直接采用替格瑞洛联合阿司匹林的治疗方案。     

三联抗血小板治疗急性冠脉综合征的临床研究

目的研究三联抗血小板方法（盐酸替罗非班＋氯吡格雷＋阿司匹林）治疗急性冠脉综合征（acute coronary syndrome,ACS）患者的有效性和安全性。方法回顾分析常规治疗组（对照组）40例和三联抗血小板治疗组（实验组）40例的临床资料。结果三联抗血小板治疗组48h和30d的主要不良心脏事件发生率明显低于对照组（包括再发心绞痛、急性心肌梗死、心源性猝死等）,小出血并发症较对照组稍高,但无统计学意义;两组的大出血并发症均未发生;两组血小板计数均无特殊变化。结论三联抗血小板治疗ACS能进一步减少心脏不良事件的发生,改善预后,而且安全性好。     

氯吡格雷中间代谢型患者使用替格瑞洛致呼吸困难1例

<正>氯吡格雷(clopidogrel)和阿司匹林(aspirin)双联抗血小板治疗已被证实能够显著降低急性冠脉综合征(ACS),尤其是经皮冠状动脉介入术(PCI)后患者的主要心血管不良事件(MACE)[1]。替格瑞洛(ticagrelor)为新型的抗血小板药物,具有起效快速和作用可逆的特点,与氯吡格雷相比,均可显著降低ACS患者(不论接受PCI或接受药     

急性冠状动脉综合征PCI术后近期交叉应用替格瑞洛和波立维的临床研究

作为冠心病,特别是急性冠脉综合征(ACS)治疗的重要手段,冠脉介入治疗(PCI)可以心肌血运重建,改善心肌缺血。PCI的成功率及患者预后不仅取决于PCI手术操作,还与积极的药物治疗和生活方式干预密切相关。双联抗血小板治疗可以降低PCI术后支架内血栓及缺血事件的发生。临床上常用的抗血小板方案主要为在阿司匹林基础上加用氯吡格雷。目前,新型口服抗血小板药--替格瑞洛已在临床上应用,临床研究已经证实了替格瑞洛较氯吡格雷能够进一步降低主要终点事件,而且出血风险并未增加［1］。但是,现在替格瑞洛尚未列入医保范围,在实际临床工作中常常遇到替格瑞洛和氯吡格雷交叉应用的现象。本文主要观察与总结ACS患者PCI术后交叉应用替格瑞洛和氯吡格雷的有效性与安全性。现报告如下。     

Emerging antiplatelet therapy for coronary artery disease and acute coronary syndrome

Antiplatelet therapy is used widely with proven benefit for the prevention of further ischemic cardiac complications in patients with known coronary artery disease (CAD) and a history of acute coronary syndrome (ACS). The limitations of conventional antiplatelet therapy with aspirin, clopidogrel, or prasugrel, as well as the fact that rates of recurrent ischemic events still remain high with use of these agents, underscore the need to investigate alternate agents that may further reduce event rates while limiting bleeding risk. The selection of antiplatelet therapy is further influenced by the following: ticagrelor was approved in July 2011 by the United States Food and Drug Administration (FDA), and clopidogrel is slated to become available as a generic productin 2012. We provide an overview of emerging agents for the treatment of CAD and ACS, including the reversible P2Y(12) antagonists ticagrelor, cangrelor, and elinogrel, and a new class of oral protease-activated receptor-1 (PAR-1) inhibitors, vorapaxar and atopaxar.The recently approved P2Y(12) antagonists prasugrel and ticagrelor demonstrate enhanced ability to prevent adverse cardiac outcomes. However, this comes at a cost of a potential increased risk of bleeding. New adverse effects have also emerged, including dyspnea for all of the reversible P2Y(12) antagonists (ticagrelor, cangrelor, and elinogrel) and ventricular pauses for ticagrelor. In addition, the newer P2Y(12) antagonists have a faster onset and offset. Two of these agents, cangrelor and elinogrel, are available as intravenous formulations, which may provide additional benefits in patients who undergo coronary artery bypass graft (CABG) surgery. Trials with the PAR-1 inhibitors have also shown trends toward reductions in cardiac events, but not without the possibility of increased bleeding. More than ever, as the arsenal of antiplatelet therapy expands, health care providers need to understand the pharmacologic and pharmacodynamic differences between conventional and emerging antiplatelet therapies for patients with ACS and CAD. Health care providers must also carefully assess patient-specific factors such as risk of thrombosis, concomitant disease states, age, drug adherence, and aspirin dose, and plan for those patients who will be undergoing CABG when selecting antiplatelet therapy in order to optimally balance bleeding and thrombosis risk.     

Ticagrelor for the treatment of arterial thrombosis

Importance of the field: High platelet reactivity has been linked to recurrent ischemic events in patients treated with conventional dual antiplatelet therapy, in patients with arterial diseases and particularly in patients treated with coronary artery stenting. The limitations of clopidogrel have served as a major rationale for the development of new P2Y₁₂ blockers that have superior pharmacodynamic profiles uninfluenced by concomitant therapies or specific genotypes. Ticagrelor is the first direct-acting reversibly binding oral P2Y₁₂ receptor antagonist. Extensive Phase II investigations have addressed the pharmacokinetic, pharmacodynamic and safety-related properties of ticagrelor compared with clopidogrel. The recently completed PLATO trial demonstrated promise for ticagrelor as a major treatment strategy for a wide spectrum of patients with acute coronary syndromes. Ticagrelor is now being reviewed by the FDA as a P2Y₁₂ receptor blocker to treat patients with coronary artery disease and, once accepted, will be in widespread use as an antiplatelet agent. Thus, it is both appropriate and timely to review available data and provide a comprehensive review of ticagrelor.

Areas covered in this review: We discuss the rationale for the development of ticagrelor, a reversible and potent P2Y₁₂ receptor blocker. The data regarding ticagrelor based on preclinical and clinical studies are examined. We researched articles about ‘AZD6140’ and ‘ticagrelor’ in PubMed from 2006 to 2010 and also reviewed data presented at recent cardiology meetings.

What the reader will gain: This is an updated and comprehensive review of ticagrelor. The advantages and disadvantages of ticagrelor and available P2Y₁₂ receptor blockers such as clopidogrel and prasugrel are discussed, thus providing a clear picture to readers.

Take home message: Ticagrelor has an important role as an antiplatelet agent in the settings of acute coronary syndrome and percutaneous coronary intervention and once accepted will be in widespread use.     

Ticagrelor: Positive,negative and misunderstood properties as a new antiplatelet agent

相似文献   

CYP2C19基因检测指导急性冠脉综合征患者抗血小板个体化治疗的药物经济学系统评价

摘 要 目的：系统评价CYP2C19基因检测指导急性冠脉综合征患者抗血小板个体化治疗的药物经济学特性,为临床药物基因型合理检测及相关卫生决策提供参考。方法：计算机检索PubMed、Embase、The Cochrane Library、WanFang Data、CNKI、VIP数据库关于CYP2C19基因型检测指导急性冠脉综合征患者抗血小板个体化治疗的药物经济学文献,检索时限均为建库至2018年5月。由两名研究者独立筛选文献、评价纳入研究的方法学质量,提取纳入研究的相关数据进行系统分析。 结果：最终纳入13项研究,仅1篇为成本 效用分析,其余均为成本 效果分析,13项研究中2项来自中国。10项研究均显示基因检测指导个体化抗血小板治疗（其中有1项是基因检测联合血小板功能测定;但1项来自中国的研究显示若患者为自费或为上海市医保,经验性使用替格瑞洛更具经济学优势,而基因指导方案在全国范围的医保患者中更具药物经济学优势）更具成本效果优势。有3项研究表明经验性全部使用替格瑞洛（其中1项是药师参与药物治疗管理联合经验性使用替格瑞洛）更具成本效果优势。结论：CYP2C19基因型检测指导急性冠脉综合征患者抗血小板个体化治疗总体具有良好的经济学优势,但鉴于文献数量及质量限制,结论仍需更多高质量的经济学研究进一步支持。     

Vorapaxar: a novel protease-activated receptor-1 inhibitor

INTRODUCTION: Platelet activation and reactivity are pivotal for both acute and chronic atherothrombotic event occurrences. AREAS COVERED: Only 20% relative risk (～ 2% absolute risk) reduction associated with newer P2Y(12) receptor blocker therapy such as prasugrel and ticagrelor compared with clopidogrel indicates that dual antiplatelet therapy may be associated with a ceiling effect in attenuating platelet-mediated ischemic event occurrence and that residual ischemic event occurrences are mediated by other pathways that are unblocked by current antiplatelet therapy. Therefore, inhibition of the thrombin-protease-activated receptor (PAR)-1 interaction may provide additional benefits in attenuating ischemic event occurrence in selected patients. There are two major PAR-1 blockers are under investigations - vorapaxar and atopaxar. In preclinical and Phase I - II studies, inhibition of thrombin-mediated platelet activation by a PAR-1 inhibitor, in general, has added to the antithrombotic efficacy of aspirin and clopidogrel without increasing bleeding. However, intracranial hemorrhage in patients with a history of stroke associated with vorapaxar and hepatic toxicity associated with atopaxar are important concerns. EXPERT OPINION: At this time, the specific role of PAR-1 inhibitor in the settings of percutaneous coronary intervention and acute coronary syndrome, both during the acute setting and as a long-term therapeutic agent, is not clear. Although the PAR-1 inhibitors are associated with less bleeding, its effectiveness as an antithrombotic agent and also side effects are major concerns. Future large-scale trials with goals addressing these concerns are needed to define the specific role of PAR-1 receptor inhibitor.     

A comprehensive comparative review of adenosine diphosphate receptor antagonists

INTRODUCTION: Thrombosis risk necessitates dual antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) receptor antagonist, in patients who have acute coronary syndrome. Current guidelines emphasize the critical role of dual antiplatelet therapy in both medical management and invasive strategy, especially in patients undergoing percutaneous coronary intervention. With the availability of multiple ADP-receptor antagonists, it is crucial to select the most appropriate agent for each patient. AREAS COVERED: The pertinent trials were identified through a MEDLINE search, in addition to a manual search from the articles retrieved. This review examines the differences between clopidogrel, prasugrel and ticagrelor in terms of their pharmacological/pharmacokinetic properties, clinical efficacy, drug interactions and safety parameters. EXPERT OPINION: Prasugrel and ticagrelor exhibit greater platelet inhibition and superior efficacy compared with clopidogrel, at the expense of higher bleeding risk. Prasugrel and ticagrelor should be preferred over clopidogrel in patients who are at a high risk of thrombotic events with low risk of bleeding. Additionally, these two agents may offer advantage over clopidogrel in those patients who might have risk for drug resistance due to CYP2C19 polymorphism. In selecting the ideal agent for patients, clinicians should tailor the antiplatelet regimen by considering individual risk factors and medication characteristics.     

Ticagrelor for acute coronary syndrome?

Current guidelines from the National Institute for Clinical Excellence (NICE) recommend antiplatelet therapy comprising aspirin plus either clopidogrel or prasugrel for patients with acute coronary syndrome (ACS). However, such dual therapy increases the likelihood of bleeding compared to that with aspirin alone. Ticagrelor (Brilique - Astra-Zeneca) is a new oral antiplatelet drug recently licensed in the UK (since publication of the NICE guidelines) for use with aspirin in patients with ACS, including those managed medically or undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Here we review the place of ticagrelor in the management of people with ACS, and whether it offers advantages over standard therapy in terms of greater efficacy or lower likelihood of bleeding complications.     

临床药师在冠心病患者抗血小板药物治疗中的作用

目的 探讨临床药师在冠心病患者进行抗血小板药物治疗中的作用.方法 临床药师参与1例急性冠脉综合征及1例心肌梗死患者的抗血小板药物治疗,查阅相关文献,探讨了如何在不能耐受阿司匹林的情况下进行替代治疗及替格瑞洛与氯吡格雷如何正确的桥接使用,为患者制定更有效的抗血小板药物治疗方案提供了建议.结果 医师采纳了临床药师的建议,患者通过治疗,情况好转出院.结论 临床药师参与临床药物治疗,促进了临床用药的合理、有效,也为如何制定个体化的抗血小板治疗方案提供了参考.     

Review of clopidogrel dose escalation in the current era of potent P2Y12 inhibitors

Dual anti-platelet therapy with aspirin and a P2Y12 inhibitor is the standard of care for patients with acute coronary syndromes (ACS) and for patients undergoing percutaneous coronary intervention (PCI). Clopidogrel is associated with increased risk of high on-treatment platelet reactivity (HTPR) compared to ticagrelor and prasugrel. Investigators have therefore sought to “escalate” clopidogrel dosing to overcome HTPR to reduce ischemic/thrombotic events. In this review, we will summarize the evidence for dose escalation in the context of genetic determinants of resistance and platelet function data. We will review contemporary clinical trials that have sought to improve delivery of dual antiplatelet therapy to patients with coronary artery disease and discuss the potential of clopidogrel dose escalation in specific populations.     

Pharmacokinetics and pharmacodynamics of ticagrelor in the treatment of cardiac ischemia

Introduction: After acute coronary syndromes (ACS), the so-called dual antiplatelet therapy (DAPT), which usually consists of low-dose of aspirin in combination with a thienopyridine (clopidogrel, prasugrel) or with a cyclopentyltriazolopyrimidine (ticagrelor), reduces the risk of ischemic events. Ticagrelor, un particular, is an effective drug as it isn’ a prodrug, doesn’t require metabolic activation and demonstrates a rapid onset and faster offset of action.

Areas covered: This article evaluates the pharmacokinetics, efficacy, safety and tolerability of ticagrelor during DAPT after ACS and its potential use beyond the canonical twelve months after PCI. The review discusses studies comparing: ticagrelor and clopidogrel (DISPERSE, DISPERSE-2, PLATO, RESPOND Trial, ONSET/OFFSET Trials), ticagrelor and placebo (PEGASUS TIMI 54 Trial).

Expert opinion: For ACS patients, the PLATO trial showed that ticagrelor was superior to clopidogrel in the reduction of cardiovascular death, myocardial infarction and stroke. PEGASUS TIMI 54 showed that patients in whom ischemic events and cardiovascular death outweigh the risk of life-threatening bleeding, may benefit from prolonged ticagrelor-based dual antiplatelet therapy, over 12 months. This strategy has been recently approved by the ACC/AHA guidelines. Further studies are needed to evaluate and eventually validate the role of the prolonged DAPT in patients treated with new generation stents.