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。     

CYP2C19基因中间代谢型ACS患者双倍剂量氯吡格雷和标准剂量替格瑞洛疗效与安全性评价

目的：探讨CYP2C19中间代谢型急性冠脉综合征（ACS）患者双倍剂量氯吡格雷和标准剂量替格瑞洛的疗效与安全性。方法：就诊的ACS患者,排除未行PCI手术、重度肝功能不全患者,对568例患者进行CYP2C19基因检测,其中CYP2C19中间代谢型患者252例（占比44.37%）,22例因各种原因（包括经济因素等）未接受PCI治疗,最终将230例CYP2C19中间代谢型患者（占比40.49%）随机分配至双倍剂量氯吡格雷组和标准剂量替格瑞洛组,并对2组患者进行长达12个月的随访,统计分析2组患者主要终点事件、出血事件和呼吸困难事件发生率差异。结果：随访1,6,12个月时2组患者主要终点事件发生率方面无显著差异（P＞0.05）。出血事件发生率替格瑞洛组稍高于氯吡格雷组,但无显著性差异（P＞0.05）。替格瑞洛组有2例发生致命颅内出血事件,可能原因是患者为出血高风险人群。呼吸困难发生率标准剂量替格瑞洛组显著高于双倍剂量氯吡格雷组（P<0.05）。替格瑞洛组6例患者发生显著的呼吸困难,导致患者无法耐受均转换成氯吡格雷。结论：CYP2C19基因中间代谢型ACS患者双倍剂量氯吡格雷和标准剂量替格瑞洛疗效无显著性差异。安全性方面,2组患者出血事件无显著性差异,但替格瑞洛组严重出血事件高于氯吡格雷组;呼吸困难发生率标准剂量替格瑞洛组显著高于双倍剂量氯吡格雷组。基于本研究结果,谨慎建议对于CYP2C19基因中间代谢型患者,无出血风险高危因素时,双倍剂量氯吡格雷和标准剂量替格瑞瑞洛均可选择;出血高风险人群,建议选择氯吡格雷。对于使用替格瑞洛过程中发生呼吸困难,建议及时更换为双倍剂量氯吡格雷。     

血栓弹力图评价替格瑞洛对氯吡格雷低反应患者血小板抑制的影响

目的探讨经皮冠状动脉介入(PCI)术后,经血栓弹力图(TEG)检测的氯吡格雷药物低反应患者,换用替格瑞洛治疗后的血小板抑制情况。方法因冠心病不稳定型心绞痛行PCI术的患者常规氯吡格雷联合阿司匹林抗栓,经TEG筛选出53例氯吡格雷抑制不敏感、阿司匹林抑制正常的患者,换用替格瑞洛联合阿司匹林治疗。使用TEG比较换药前后花生四烯酸(AA)诱导的血小板抑制率及二磷酸腺苷(ADP)诱导的血小板抑制率。结果经TEG检测的氯吡格雷药物低反应患者,在换用替格瑞洛后,由ADP诱导的血小板抑制率明显升高[(41±8)%与(70±11)%],差异有统计学意义(P<0.01)。换用替格瑞洛前后由AA诱导的血小板抑制率变化差异无统计学意义(P>0.05)。结论对于血小板高反应性的患者,每天75mg氯吡格雷不能满足血小板抑制效果,换用替格瑞洛能够有效减低药物低反应的发生率,明显改善血小板抑制效果。     

PCI术后患者抗血小板治疗方案的药物经济学评价

目的 从医疗保险角度,对经皮冠脉支架置入（percutaneous coronary intervention,PCI）术后3种抗血小板药物治疗方案进行经济学评价。方法 3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,或根据CYP2C19基因型指导选择国产氯吡格雷或替格瑞洛,由此建立决策树模型并进行成本效果分析,预测该3种方案避免主要心血管事件的发生率以及成本,研究时间为1年。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的经济性最好。结论 对于PCI术后的患者,最推荐直接采用替格瑞洛联合阿司匹林的治疗方案。     

分站式杂交冠状动脉血运重建术后替格瑞洛和氯吡格雷抗血小板聚集疗效与安全性的比较

目的比较分站式杂交冠状动脉血运重建术(HCR)后应用替格瑞洛或氯吡格雷抗血小板聚集的疗效与安全性。方法采用前瞻性随机对照研究方法, 根据术后抗血小板治疗方案将在我院接受分站式HCR治疗的冠状动脉多支病变患者分为替格瑞洛组(术后予阿司匹林肠溶片100 mg口服、1次/d, 替格瑞洛片90 mg口服、2次/d, 连续服用1年)与氯吡格雷组(术后予阿司匹林肠溶片100 mg口服、1次/d, 硫酸氢氯吡格雷片75 mg、1次/d, 连续服用1年)。分析比较2组患者一般情况、手术前后不同时点血小板聚集功能[血小板最大聚集率(MPAR)、P2Y12反应单位(PRU)], 术后血小板抑制率[阿司匹林抵抗(AA)、替格瑞洛或氯吡格雷抵抗(ADP)], 主要心血管不良事件(MACE)、出血事件和不良反应发生情况。结果纳入本研究的患者共124例, 替格瑞洛组和氯吡格雷组各62例, 2组患者基线资料(性别、年龄、纽约心脏病协会心功能分级、合并疾病等)的差异均无统计学意义(均P>0.05)。替格瑞洛组和氯吡格雷组术后24 h、7 d、1个月MPAR均低于术前[(50±9)%、(36±8)%、(29±6)...     

CYP2C19基因导向的抗血小板药物治疗方案在急性冠状动脉综合征患者中的经济学评价

目的： 从药物经济学角度评价拟行介入手术的急性冠脉综合征患者依据CYP2C19基因指导抗血小板药物应用的可行性。方法： 采用回顾性分析,选取皖南医学院弋矶山医院2018年4月至2020年4月收治的513例采用氯吡格雷联合阿司匹林或替格瑞洛联合阿司匹林进行抗血小板治疗的急性冠脉综合征住院患者,根据是否进行CYP2C19基因检测及个体化用药指导,非随机分为个体化治疗组和采用氯吡格雷标准剂量的常规治疗组。成本仅包括直接医疗成本,效果指标采用患者1年内发生主要心血管不良事件次数,进行增量成本效果分析和敏感性分析。结果： 个体化治疗组（n=312）的人均总治疗费用为49 319元,常规治疗组（n=201）为51 820元;1年内再入院率个体化治疗组为12.18%,常规治疗组为21.89%,具有统计学差异（P<0.05）。增量成本效果比为257.5元/%,相比常规治疗组,个体化治疗组每使100个患者中减少1例因发生主要心血管不良事件再入院,可少花费25 750元,表明个体化治疗策略具有明显的成本-效果优势。敏感性分析表明,提高用药效果对增量成本效果比的改变并不十分显著,提示医疗费用才是影响基因检测经济性的关键因素。结论： 通过CYP2C19基因检测指导的抗血小板治疗方案对急性冠脉综合征患者经皮冠状动脉介入术后预防主要心血管不良事件具有良好效果,并具有明显成本-效果收益,更具有药物经济学优势。     

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...     

替格瑞洛与氯吡格雷联合阿司匹林对糖尿病合并急性脑梗死患者神经功能恢复及血清VEGF、MMP-9、Ang-Ⅱ的影响

目的研究比较替格瑞洛与氯吡格雷联合阿司匹林对糖尿病合并急性脑梗死(DACI)患者神经功能恢复及血管内皮生长因子(VEGF)、基质金属蛋白酶9(MMP-9)、血管紧张素Ⅱ(Ang-Ⅱ)的影响。方法选取DACI患者193例,随机分为替格瑞洛组(97例)和氯吡格雷组(96例)。在常规治疗的基础上,两组患者均给予阿司匹林肠溶片(100 mg·d~(-1),qd),同时分别给予替格瑞洛(90 mg·d~(-1),bid)或氯吡格雷(75 mg·d~(-1),qd),连续用药14 d。观察患者治疗前后美国国立卫生院神经功能缺损(NIHSS)评分、血小板聚集率和血清VEGF、MMP-9、Ang-Ⅱ水平变化情况。结果与治疗前比较,两组NIHSS评分、血小板聚集率、MMP-9、Ang-Ⅱ水平均显著下降(P<0.01),且替格瑞洛组NIHSS评分、血小板聚集率、MMP-9、Ang-Ⅱ水平明显低于氯吡格雷组(P<0.05,P<0.01);两组VEGF水平均显著上升(P<0.01),且替格瑞洛组明显高于氯吡格雷组(P<0.01)。结论替格瑞洛与氯吡格雷联合阿司匹林治疗均可改善DACI患者的神经功能,预防脑梗死发生,替格瑞洛效果优于氯吡格雷。     

替格瑞洛联合急诊经皮冠状动脉介入治疗对ST段抬高型心肌梗死患者心肌损伤及血小板聚集程度的影响

目的 研究替格瑞洛联合急诊经皮冠状动脉介入(PCI)治疗对ST段抬高型心肌梗死(STEMI)患者心肌损伤、血小板聚集程度的影响.方法 选择接受PCI治疗的108例STEMI患者作为研究对象,采用随机数字表法分为替格瑞洛组和氯吡格雷组,分别接受PCI联合替格瑞洛治疗以及PCI联合氯吡格雷治疗.PCI术后评估心肌血流灌注情况,检测血清中心肌损伤指标以及血小板聚集指标.结果 PCI术后,替格瑞洛组患者的冠状动脉狭窄程度(TIMI)分级和心肌灌注(TMPG)分级均显著高于氯吡格雷组,校正TIMI帧计数(CTFC)以及无复流率均显著低于氯吡格雷组;PCI术后12h时,替格瑞洛组患者血清中肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、肌钙蛋白Ⅰ(cTnⅠ)、肌钙蛋白T(cTnT)、血小板活化因子(PAF)、血小板α颗粒膜蛋白-140(GMP-140)、血栓素B2(TXB2)的含量显著低于氯吡格雷组,6-酮-前列腺素F1α(6-keto-PGF1α)的含量显著高于氯吡格雷组.结论 急诊PCI围手术期应用替格瑞洛治疗STEMI能够更为有效的改善心肌血流灌注、减轻心肌细胞损伤、抑制血小板聚集.     

新型P2Y12受体抑制剂替格瑞洛临床研究进展

抗血小板药物是急性冠脉综合征（Acute Coronary Syndrome,ACS）治疗的基石,对防治心肌缺血和介入并发症是有益的。目前治疗ACS和经皮冠状动脉介入治疗（percutaneous coronary intervention,PCI）指南推荐使用的口服抗血小板药物包括氯吡格雷、替格瑞洛、普拉格雷联合阿司匹林双重抗血小板治疗预防复发性缺血事件。本文对新型P2Y12受体抑制剂替格瑞洛的药代动力学和药效学特点以及在ACS患者中的循证医学证据作一介绍。     

Assessment of VerifyNow P2Y12 assay accuracy in evaluating clopidogrel-induced platelet inhibition

The emergence of point-of-care assays enabling bedside testing such as the VerifyNow P2Y12 system might prove useful in clinical settings. The aim of this study was to evaluate the ability of the VerifyNow P2Y12 assay to estimate the inhibition of platelet aggregation provided by clopidogrel in the absence of baseline off-drug aggregation data. Sixty-eight patients with coronary artery disease scheduled to initiate clopidogrel therapy underwent platelet aggregation testing by VerifyNow P2Y12 at baseline and after clopidogrel administration. The inhibition reported by the VerifyNow assay (relative to thrombin receptor activating peptide-induced platelet aggregation, serving as baseline) was compared with that calculated with the actual adenosine diphosphate-induced baseline obtained with the same methodology. The postclopidogrel thrombin receptor activating peptide-induced aggregation showed a great discordance with that induced by adenosine diphosphate before clopidogrel with a bias of 24 units (95% limits of agreement from -142 to 190 units). Moreover, the inhibition reported by the assay overestimated the standard before-and-after testing data by an average of 8% (95% limits of agreement from -49% to 65%), making its use without a true baseline comparator unsatisfactory. The VerifyNow P2Y12 assay fails to accurately quantify platelet inhibition achieved by clopidogrel compared with before-and-after testing. Further studies are required to establish the clinical usefulness of the VerifyNow P2Y12 assay to accurately predict the occurrence of major adverse cardiovascular events in patients with reduced clopidogrel efficacy before it can be implemented in clinical practice. At present, the use of this assay in clinical care cannot be recommended for monitoring clopidogrel therapy.     

血栓弹力图法和VerifyNow P2Y12法评估CYP2C19基因多态性对氯吡格雷反应性的影响

目的：通过血栓弹力图法（TEG）和VerifyNow P2Y12法检测来评估CYP2C19基因多态性对急性冠脉综合征（ACS）患者服用氯吡格雷疗效的影响，并比较2种方法检测结果的差异。方法：入选2017年10月至2018年10月因ACS入院且服用氯吡格雷（75 mg·d^-1）和阿司匹林（100 mg·d^-1）的患者230例，使用焦磷酸测序检测其CYP2C19基因型，并在服用氯吡格雷7 d后，使用TEG法检测其二磷酸腺苷（ADP）诱导的血小板聚集抑制率和VerifyNow P2Y12法检测其血小板反应单位（PRU）。结果：TEG法结果显示CYP2C19快代谢型、中间代谢型和慢代谢型患者出现氯吡格雷抵抗的比例分别为8.9%、40.2%和59.4%。VerifyNow P2Y12法检测结果显示各代谢型患者出现氯吡格雷抵抗的比例分别为6.9%、29.9%和50.0%。慢代谢型及中间代谢型患者出现氯吡格雷抵抗的概率明显高于快代谢组（P<0.05）。2种方法氯吡格雷抵抗检出率差异无显著性（P>0.05），检测结果显著相关（r=-0.719，P<0.001）。结论：CYP2C19基因多态性显著影响ACS患者服用氯吡格雷的疗效。TEG法和VerifyNow P2Y12法检测抗血小板聚集结果具有相关性。     

急性冠脉综合征患者替格瑞洛与氯吡格雷 相互转换治疗的现状调查分析

目的：调查分析急性冠脉综合征（ACS）急性期或早期的患者在住院期间替格瑞洛与氯吡格雷相互转换的应用现状。方法：分析2019年6月~12月本院急性期或早期ACS患者院内替格瑞洛与氯吡格雷相互转换的发生率、一般临床特征、转换给药时间和给药剂量。结果：ACS患者替格瑞洛与氯吡格雷转换治疗的比率为12.9%（208/1607），最终纳入的182例患者中，63.2%（115例）由氯吡格雷换为替格瑞洛（升阶治疗组），36.8%（67例）由替格瑞洛换为氯吡格雷（降阶治疗组）。升阶组和降阶组的一般临床特征存在一定的差异；两组患者均在造影术后当天至术后第一天的时间段发生转换的人数最多，且组间存在差异（58.4% vs 40.0%，P=0.018）；降阶组仅有35.5%的患者在最后一剂替格瑞洛给药24 h后给予首剂氯吡格雷；仅有37.4%的患者在转换时给予所换用P2Y12受体拮抗剂的负荷剂量。结论：“指南”推荐的P2Y12受体拮抗剂转换策略尚未得到广泛认可，临床实践中转换策略的制定须结合患者情况作个体化选择。     

急性冠脉综合征患者替格瑞洛与氯吡格雷 相互转换治疗的现状调查分析

目的：调查分析急性冠脉综合征（ACS）急性期或早期的患者在住院期间替格瑞洛与氯吡格雷相互转换的应用现状。方法：分析2019年6月~12月本院急性期或早期ACS患者院内替格瑞洛与氯吡格雷相互转换的发生率、一般临床特征、转换给药时间和给药剂量。结果：ACS患者替格瑞洛与氯吡格雷转换治疗的比率为12.9%（208/1607）,最终纳入的182例患者中,63.2%（115例）由氯吡格雷换为替格瑞洛（升阶治疗组）,36.8%（67例）由替格瑞洛换为氯吡格雷（降阶治疗组）。升阶组和降阶组的一般临床特征存在一定的差异;两组患者均在造影术后当天至术后第一天的时间段发生转换的人数最多,且组间存在差异（58.4% vs 40.0%,P=0.018）;降阶组仅有35.5%的患者在最后一剂替格瑞洛给药24 h后给予首剂氯吡格雷;仅有37.4%的患者在转换时给予所换用P2Y12受体拮抗剂的负荷剂量。结论：“指南”推荐的P2Y12受体拮抗剂转换策略尚未得到广泛认可,临床实践中转换策略的制定须结合患者情况作个体化选择。     

Ticagrelor in ST-elevation myocardial infarction

Ticagrelor is a new oral antagonist of the platelet P2Y12 receptor that offers several potential advantages compared to clopidogrel including faster and more effective inhibition of platelet aggregation. Ticagrelor has been compared to clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial in a broad population of patients with acute coronary syndrome showing a reduction of the 12-month risk of death from vascular causes, myocardial infarction and stroke without increasing the overall risk of major bleeding. In a subanalysis of the PLATO trial focusing on patients with ST-elevation myocardial infarction, ticagrelor results were consistent with those of the overall trial. Additionally, possible pleiotropic effects of ticagrelor, including an appealing interaction with adenosine, might constitute a specific advantage in this particular subset of patients.     

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.     

Pharmacokinetic, pharmacodynamic and pharmacogenetic profile of the oral antiplatelet agent ticagrelor

Acute coronary syndromes (ACS) remain life-threatening disorders associated with high morbidity and mortality, despite advances in treatment over the last decade. Adenosine diphosphate-induced platelet activation via P2Y(12) receptors plays a pivotal role in the pathophysiology of ACS. The current standard of treatment involves dual antiplatelet therapy with aspirin (acetylsalicylic acid) and the thienopyridine clopidogrel. Numerous studies and wide use in clinical practice have established the value of this approach in the treatment of ACS. However, clopidogrel treatment has a number of limitations, including a delayed onset of action due to the need for metabolic activation, variable and reduced antiplatelet effects in patients with certain genotypes, and prolonged recovery of platelet function due to irreversible P2Y(12) receptor binding. Prasugrel, a new thienopyridine, has demonstrated more consistent inhibition of platelet aggregation (IPA) than clopidogrel, although this thienopyridine also requires metabolic activation and treatment is associated with a significantly increased risk of life-threatening and fatal bleeding. The recently approved oral antiplatelet agent ticagrelor has the potential to overcome some of the limitations of current therapy due to its unique pharmacokinetic and pharmacodynamic profiles. It is a member of a new chemical class, the cyclopentyltriazolopyrimidines, and is a potent P2Y(12) receptor antagonist. Ticagrelor is rapidly absorbed, with a median time to maximum concentration of 1.3-2.0 hours. Ticagrelor does not require metabolic activation to an active form and binds rapidly and reversibly to the P2Y(12) receptor. As well as exerting effects via platelet P2Y(12) receptors, ticagrelor may confer additional benefits via inhibition of non-platelet P2Y(12) receptors. The pharmacokinetic profile of ticagrelor is not significantly affected by age, gender or administration with food, nor by prior treatment with, or responsiveness to, clopidogrel. Ticagrelor is primarily metabolized via the cytochrome P450 (CYP) 3A4 enzyme, rapidly produces plasma concentration-dependent IPA that is greater and more consistent than that observed with clopidogrel, and can also enhance platelet inhibition and overcome non-responsiveness in patients previously treated with clopidogrel. Importantly, the pharmacodynamic characteristics of ticagrelor are not influenced by CYP2C19 and ABCB1 genotypes. This article summarizes our current knowledge regarding the pharmacokinetic, pharmacodynamic and pharmacogenetic profile of ticagrelor.     

Platelet hyperreactivity and stent thrombosis in patients undergoing coronary stenting

Stent thrombosis (ST) is a rare but very serious event complicating percutaneous coronary intervention (PCI) procedures. Both procedure- and patient-related factors, including inadequate platelet inhibition are well known predictors of ST. According to the present guidelines, a dual antiplatelet treatment regimen consisting of aspirin and a P2Y12 receptor inhibitor such as clopidogrel, prasugrel or ticagrelor is routinely administered to ACS patients and to patients undergoing PCI in order to prevent thrombotic vessel occlusions. In recent years, evidence has grown that patients showing high on-treatment platelet reactivity (HPR) under clopidogrel intake exhibit a higher risk for the occurrence of ischemic events including ST. For assessing HPR, different platelet function assays are currently available and have already found their way into routine clinical practice in several centers. Along with this development, more potent P2Y12 receptor inhibitors like prasugrel and ticagrelor are substitutes for clopidogrel in specific circumstances such as in ACS patients or in patients who do not adequately respond to standard clopidogrel treatment. Utilizing platelet function monitoring, patients showing HPR can be identified and an optimized antiplatelet treatment regime can be tailored for these patients. This review paper aims to summarize the important facts in relation to ST and antiplatelet therapy with a particular focus on P2Y12 receptor inhibition and its ex vivo assessment in patients undergoing coronary stent placement.     

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.     

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.