替卡格雷首次显示可以比氯吡格雷更能降低急性冠脉综合征患者的心血管死亡

关于PLATO研究的报告显示新口服抗血小板药物替卡格雷(ticagrelor,Brilinta)可以降低心血管事件(心血管死亡、心肌梗死、中风)发生率(11.7%),而且比氯吡格雷更有效(clopidogrel,Plavix)(9．8％),此外替卡格雷并不会增加主要出血事件.有效终点为心血管死亡 和心肌梗死都显著减少,而中风并无差异.     

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。     

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     

新药替卡格雷与普拉格雷及其克服氯吡格雷抵抗的研究进展

目的对新型抗血小板凝集药普拉格雷和替卡格雷及它们与原有抗血小板聚集药氯吡格雷的异同及克服氯吡格雷抵抗作用进行综述。方法参阅最新国内外公开发表的相关文献,阐述新药普拉格雷和替卡格雷的研发思路及作用特点,比较它们与原有抗血小板聚集药氯吡格雷的异同,论述其克服氯吡格雷抵抗的作用机制所在。结果相对于氯吡格雷,新型抗血小板聚集药普拉格雷和替卡格雷更加强力有效,并可明显降低甚至避免氯吡格雷抵抗事件的发生。结论国际知名制药公司对普拉格雷和替卡格雷的研发理念可带给我们新启示,这些新型抗血小板聚集药为临床医师提供了新的用药选择。     

新型血小板P2Y12受体拮抗药

抑制ADP诱导的血小板聚集的药物(如氯吡格雷)已成为目前心血管领域内最重要的抗血小板药物。但氯吡格雷起效较慢,抗血小板作用相对较弱,尚有一定的低反应者和无反应者。普拉格雷是一个较新的血小板P2Y12受体拮抗药。TRITON-TIMI 38研究表明普拉格雷可使主要终点发生率(心血管死亡、非致死性心肌梗死、非致死性卒中)降低19%,但使出血并发症增加。坎格雷洛,替格雷洛,依诺格雷是更新的血小板P2Y12受体拮抗药。     

替格瑞洛对PCI术后氯吡格雷抵抗患者血小板聚集率的影响

目的探讨对经皮冠状动脉介入(PCI)治疗术后氯吡格雷抵抗的患者以替格瑞洛替换氯吡格雷治疗后血小板聚集率的变化。方法用比浊法测定血小板聚集率,筛选出PCI术后氯吡格雷抵抗患者50例,将氯吡格雷(75 mg/d)替换为替格瑞洛(90 mg,2次/d),观察血小板聚集率变化及主要不良心血管事件和出血情况。结果所有患者在替格瑞洛服用后7、30、90 d与服用前相比,血小板聚集率均明显下降,差异有统计学意义(P<0.05)。治疗期间无主要不良心血管事件及严重出血事件发生。结论对于氯吡格雷抵抗患者,替格瑞洛能明显降低血小板聚集率,疗效确切,安全性好。     

氯吡格雷和替罗非班联用对STEMI患者血小板功能及血小板表面受体表达影响的分析

目的本试验比较氯吡格雷和替罗非班联用和单用氯吡格雷对进行冠状动脉介入术的ST段抬高型心肌梗死患者血小板功能和血小板表面受体表达的影响。方法 32名ST段抬高型心肌梗死患者纳入本研究。患者行冠状动脉介入术时均接受负荷剂量300mg的氯吡格雷和阿司匹林。然后氯吡格雷组只接受氯吡格雷抗血小板治疗。替罗非班组患者除了接受氯吡格雷治疗外同时接受替罗非班治疗。在患者进行抗血小板治疗前和治疗后24h内(平均22h)分别采集血样进行分析。将血小板聚集确定为血小板止血的主要参数,用流式细胞计测定血小板表面抗原数量。结果本研究显示两组的凝血酶原时间、部分凝血酶原时间治疗前后和治疗后组间无显著差别。替罗非班组经治疗后由腺苷和肾上腺素诱导的凝血时间分别显著延长120s和94s,但是氯吡格雷组的凝血时间没有显著变化。治疗后两组活化的血小板比例显著降低,但是治疗后组间有差异。替罗非班组CD41a表面抗原显著增加。结论行冠状动脉介入术的ST段抬高性心肌梗死患者氯吡格雷和替罗非班联合治疗相比单用氯吡格雷治疗GPIIb/IIIa受体数量的增加以及血小板活化的抑制作用更强,但是对凝血时间作用相似。     

替卡格雷:用于预行介入治疗的ACS患者优于氯吡格雷

氯吡格雷对血小板的抑制作用具有变异性和不可逆性,引发了有关该药最佳给药剂量及给药时机的争论。替卡格雷为一种更有效的     

细胞色素P450基因多态性对心血管药物疗效的影响

目的探讨细胞色素P450酶2C19基因(CYP2C19)681G/A多态性对氯吡格雷治疗冠状动脉粥样硬化性心脏病(CAHD)的影响。方法选取佛山市南海区第二人民医院心内科CADH患者274例,其中130例口服氯吡格雷,选取佛山市111例调查的自然人群为对照组,口服氯吡格雷患者中52例进行了择期经皮冠状动脉介入术(PCI)治疗,比较氯吡格雷治疗后患者各基因型与实验室氯吡格雷抵抗之间的关系,并分别比较不同基因型组间血小板聚集率、实验室氯吡格雷抵抗和不良心血管事件的再发生情况。结果氯吡格雷治疗后CYP2C19681AA型平均血小板聚集率降低幅度最小,GA型次之,GG型最高;PCI患者CYP2C19681A等位基因携带者组不良心血管事件再发率高、平均血小板聚集率降低幅度小、实验室氯吡格雷抵抗发生率高。结论 CYP2C19681G/A突变是CAHD患者口服氯吡格雷治疗疗效及预后欠佳的主要影响因素,它减弱了氯吡格雷对血小板的抑制作用。     

氯吡格雷抵抗的研究进展

［摘要］抗血小板是治疗冠心病患者的常规手段。氯吡格雷抵抗是指一些接受了标准的抗血小板治疗的患者仍然发生不良心血管事件的现象。尽管不同的研究显示氯吡格雷抵抗的发生率不同，但已证明氯吡格雷抵抗和心血管事件存在明确关系。该文主要对氯吡格雷抵抗的实验室检查、发生机制、发生率、临床意义及优化治疗方案的选择进行综述。     

替格瑞洛与氯吡格雷对STEMI患者术后炎症反应、心功能及预后的影响分析

目的 探讨替格瑞洛与氯吡格雷对ST段抬高型心肌梗死(STEMI)患者术后炎症反应、心功能及预后的影响.方法 80例STEMI患者,随机分为氯吡格雷组与替格瑞洛组,各40例.氯吡格雷组患者采取氯吡格雷治疗,替格瑞洛组患者采取替格瑞洛治疗.比较两组治疗效果,治疗前后炎症指标、心功能指标,住院时间,不良出血事件发生率、不良心...     

Ticagrelor. Acute coronary syndromes: nothing new

Several revascularisation methods are effective in patients with acute coronary syndromes. Standard antithrombotic treatment combines heparin and aspirin during the acute phase, followed by long-term aspirin therapy. The only proven advantage of adding clopidogrel is for patients who undergo angioplasty with stenting. Ticagrelor is an antiplatelet drug belonging to a different chemical class than clopidogrel. Its chemical structure resembles that of adenosine. Ticagrelor has been authorised in the European Union for patients with acute coronary syndromes, in combination with aspirin. Clinical evaluation is mainly based on a double-blind randomised trial comparing ticagrelor + aspirin versus clopidogrel + aspirin in 18 624 patients who underwent angioplasty (64% of patients), coronary artery bypass grafting (10%), or who received medical treatment only. Half of the patients were treated for at least 9 months. After 12 months of treatment, compared to the clopidogrel group, overall mortality appeared to be significantly lower in the ticagrelor group (4.5% versus 5.9%), along with cardiovascular mortality (4.0% versus 5.1%). Symptomatic myocardial infarction was also less frequent (5.8% versus 6.9%), but not stroke (about 1.4% in both groups). Ticagrelor did not statistically significantly reduce overall mortality in patients who had angioplasty with stenting, but stent thrombosis was less frequent than with clopidogrel (2.9% versus 3.8%). In combination with aspirin, ticagrelor provoked more bleeding than clopidogrel, based on the definition used in the trial (16.1% versus 14.6%). In contrast, the rate of major bleeding was similar in the two groups (11.5%), including fatal bleeding (0.3%). The adverse effect profile of ticagrelor resembles that of adenosine in certain respects. For example, dyspnoea was more frequent with ticagrelor than with clopidogrel (13.8% versus 7.8%), as were conduction disorders and ventricular pauses at the beginning of treatment (5.8% versus 3.6%). There were also more cases of hyperuricaemia and elevated creatinine levels with ticagrelor. Ticagrelor and its active metabolite are substrates and inhibitors of cytochrome P450 isoenzymes and P-glycoprotein, creating a risk of multiple pharmacokinetic interactions. Pharmacodynamic interactions are also likely to occur, especially with antithrombotic agents and heart-rate-lowering drugs. In practice, in patients with an acute coronary syndrome treated with angioplasty and stenting, and who are also receiving aspirin, it remains to be shown whether the harm-benefit balance of ticagrelor is clearly better than that of clopidogrel. In other settings, there is no firm evidence that ticagrelor is better than aspirin alone.     

Efficacy and safety of ticagrelor in patients with acute coronary syndrome: A meta‐analysis of randomized controlled trials

Acute coronary syndrome (ACS) is a dangerous and urgent clinical pattern of coronary artery disease. Aspirin and adenosine diphosphate P2Y₁₂ receptor antagonists are the standard dual anti‐platelet therapy for patients with ACS. Ticagrelor is a new oral antagonist of the adenosine diphosphate P2Y₁₂ receptor. Randomized controlled trials (RCTs) have evaluated the efficacy and safety of ticagrelor compared to clopidogrel or prasugrel in patients with ACS, obtaining conflicting results. Thus, we conducted a meta‐analysis of these RCTs to determine the efficacy and safety of ticagrelor in patients with ACS. Results of the meta‐analysis indicate that ticagrelor decreased the risk of major adverse cardiovascular events (MACE) and all‐cause death, but increased the risk of bleeding events. In Asiatic patients, analysis indicates that ticagrelor did not decrease the risk of MACE and all‐cause death, while increasing the risk of bleeding events. Together, this meta‐analysis suggests that ticagrelor was more effective, but less safe than clopidogrel and prasugrel in patients with ACS. Subgroup analysis indicates that ticagrelor was not more effective, although less safe than clopidogrel in Asiatic patients, thus more evidence is needed to further evaluate the efficacy and safety of ticagrelor in Asiatic patients.     

Ticagrelor: a review of its use in the management of acute coronary syndromes

Ticagrelor (Brilique?; Brilinta?), a cyclopentyl-triazolo-pyrimidine antiplatelet agent, is the first oral antagonist of the P2Y(12) receptor to offer reversible receptor binding. It is indicated in the EU for the prevention of atherothrombotic events in adults with acute coronary syndromes (ACS) [unstable angina pectoris, ST-segment elevation myocardial infarction [STEMI] or non-STEMI), including those managed medically or with percutaneous coronary intervention or coronary artery bypass grafting (CABG). Ticagrelor provides selective and reversible inhibition of adenosine diphosphate-induced platelet aggregation, with a faster onset and offset of action than that of clopidogrel, and is effective in the treatment of patients with ACS, with or without ST-segment elevation. In the large, randomized, double-blind, multicentre PLATO trial conducted in this patient population, ticagrelor was more effective than clopidogrel in terms of preventing ischaemic events over 12 months, providing a significantly lower risk of the primary composite endpoint of myocardial infarction, stroke or death from vascular causes, and was associated with an overall mortality benefit. The risk of major bleeding with ticagrelor, including bleeds related to CABG, did not differ from that seen with clopidogrel in this study, although ticagrelor was associated with more non-CABG-related major bleeds and fatal intracranial bleeding, albeit the latter bleeding events were rare. Further long-term and comparative efficacy and tolerability data are required to definitively position ticagrelor with respect to other antiplatelet agents, including prasugrel. However, the clinical data currently available indicate that ticagrelor is a promising option for the treatment of patients with ACS and may be of particular use in those at high risk of ischaemic events or unresponsive to clopidogrel.     

替格瑞洛治疗行PCI的ST段抬高型心肌梗死合并糖尿病患者效果观察

目的:观察行PCI治疗的ST段抬高型心肌梗死(STEMI)合并2型糖尿病(DM)患者应用替格瑞洛的有效性与安全性。方法:STEMI合并2型糖尿病患者154例,随机分为替格瑞洛组79例,氯吡格雷组75例,比较分析2组治疗1,6,12个月时全因死亡率、不良心血管事件(MACE)发生率、支架内血栓发生率、左室射血分数、出血事件及呼吸困难等指标。采用血栓弹力图检测2组患者治疗5 d时血小板抑制率和抵抗率。结果:替格瑞洛组1,6,12个月时全因病死率、MACE发生率、支架内血栓发生率较氯吡格雷组比较差异无统计学意义(P>0.05);替格瑞洛组支架内再狭窄发生率低于氯吡格雷组,左室射血分数优于氯吡格雷组(P<0.05);替格瑞洛组呼吸困难发生率高于氯吡格雷组(P<0.05),但症状轻微,无需特殊治疗;2组出血事件发生率比较差异无统计学意义(P>0.05);治疗5 d时替格瑞洛组血小板抑制率高于氯吡格雷组(69.22±12.34)% vs (46.87±22.1)%(P<0.05),血小板抵抗率低于氯吡格雷组(2.53% vs 22.67%)(P<0.05)。结论:在行PCI治疗的STEMI合并DM患者中应用替格瑞洛可改善预后,且安全性好。     

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.     

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。     

替格瑞洛对比氯吡格雷治疗东亚ACS患者有效性和安全性的Meta分析

目的:系统性评价替格瑞洛对比氯吡格雷治疗东亚急性冠状动脉综合征(ACS)患者的有效性和安全性,旨在为临床用药提供循证参考。方法:计算机检索Cochrane图书馆、PubMed、Embase、中国知网、万方数据库等,收集替格瑞洛(试验组)对比氯吡格雷(对照组)治疗东亚ACS患者的随机对照试验(RCT)。筛选文献、提取数据后采用Cochrane系统评价员手册5.1.0推荐的偏倚风险评估工具对纳入文献进行质量评价,采用Rev Man 5.3统计软件进行Meta分析。结果:共纳入5项RCT,共计4511例患者。Meta分析结果显示,两组患者主要心血管不良事件发生率[OR=0.85,95%CI(0.68,1.04),P=0.12]、心血管原因死亡率[OR=0.76,95%CI(0.57,1.03),P=0.08]、脑卒中发生率[OR=0.77,95%CI(0.48,1.24),P=0.28]比较,差异均无统计学意义;试验组患者主要出血事件发生率[OR=1.54,95%CI(1.19,1.99),P=0.001]、次要出血事件发生率[OR=1.80,95%CI(1.40,2.32),P<0.00001]均显著高于对照组。结论:替格瑞洛在降低东亚ACS患者的主要心血管不良事件、心血管原因死亡以及脑卒中的发生风险等方面的作用与氯吡格雷相当,但该药会增加患者主要出血、次要出血事件的发生风险。     

替格瑞洛对急性冠脉综合征经皮冠状动脉介入治疗围术期血小板聚集率的影响

目的 探讨替格瑞洛对急性冠脉综合征(ACS)经皮冠状动脉介入治疗(PCI)围术期血小板聚集率(MPAR)的影响.方法 80例确诊为ACS行PCI术患者为研究对象,术前采用随机数字表法分为替格瑞洛治疗组(观察组)和氯吡格雷治疗组(对照组),每组40例.所有研究对象入院前已连续服用氯吡格雷(泰嘉) 75 mg·d-1持续7 d以上者维持原剂量,未曾服用过氯吡格雷者予以300 mg负荷剂量后75 mg·d-1维持.观察组入院前已连续服用替格瑞洛每次90 mg,2次/天,持续7 d以上者维持原剂量,未曾服用过替格瑞洛者予以180 mg负荷剂量后改标准剂量替格瑞洛(每次90 mg,2次/天)治疗.分别于治疗前、术后5 d抽取空腹外周血标本进行MPAR的测定.结果 治疗前观察组和对照组患者MPAR比较,差异无统计学意义 (P>0.05);术后5 d外周血MPAR均明显低于治疗前(P<0.05);观察组MPAR明显低于对照组(P<0.05).结论 替格瑞洛较氯吡格雷能更好地抑制ACS血管病变患者PCI围术期MPAR,降低早中期不良心血管事件的发生率,对重度冠状动脉血管病变的患者具有更好抗血小板聚集的治疗效果.