替格瑞洛药物利用评价标准的构建和应用

目的 建立替格瑞洛药物利用评价(drug use evaluation,DUE)标准,为临床合理应用替格瑞洛提供参考。方法 以替格瑞洛说明书为基础,参考相关指南、专家共识和文献,并通过专家咨询法,从用药指征、用药过程和用药结果3个方面建立替格瑞洛的DUE标准。采用回顾性研究法,对某三甲医院2021年1月—12月使用替格瑞洛的病历进行合理用药评价。结果 建立的替格瑞洛DUE标准分为三级,包括一级指标3项,二级指标14项,三级指标60项。共纳入使用替格瑞洛的病例263例,其中不合理率为72.62%,不合理情况主要为超适应证用药(60.08%)、药物转换(14.83%)和用法用量(5.70%)等方面。结论 建立的替格瑞洛DUE标准有较强的科学性、实用性和可行性,可为临床合理用药和处方点评提供参考依据。     

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。     

替格瑞洛和氯吡格雷在老年冠心病患者抗血小板治疗中有效性及安全性的Meta分析

目的：探讨替格瑞洛和氯吡格雷在老年冠心病患者抗血小板治疗中的疗效及安全性,阐明更合理的抗血小板治疗策略。方法：应用计算机检索Cochrane试验资料库、Ovid-Medline全文数据库、EMBase数据库、PubMed数据库、中国学术文献总库（CNKI）、万方数字化期刊库、维普数据库（VIP）及中国生物医学文献数据库（CBM）,收集分为替格瑞洛组和氯吡格雷组治疗老年冠心病的随机对照试验（RCT）,2组患者分别给予替格瑞洛联合其他药物及氯吡格雷联合其他药物治疗,应用RevMan5.3统计软件进行Meta分析,观察抗血小板治疗有效性相关不良事件[即主要心血管不良事件（MACE）、心肌梗死（MI）、支架内血栓、全因死亡及卒中]和安全性相关不良事件（出血事件）的发生情况。结果：按照纳入和排除标准,共纳入15篇符合入选标准的RCT。Meta分析,与氯吡格雷组比较,替格瑞洛组MACE发生率（RR=0.59,95% CI：0.46~0.76,Z=4.08,P<0.01）、MI发生率（RR=0.48,95% CI：0.28~0.81,Z=2.74,P=0.006）、支架内血栓发生率（RR=0.16,95% CI：0.06~0.48,Z=3.30,P=0.001）和全因死亡发生率（RR=0.52,95% CI：0.30~0.89,Z=2.41,P=0.02）均明显降低,卒中发生率（RR=0.76,95% CI：0.39~1.47,Z=0.81,P=0.42）差异无统计学意义,出血发生率（RR=1.57,95% CI：1.20~2.05,Z=3.28,P=0.001）明显增加。结论：对于老年冠心病患者,替格瑞洛抗血小板治疗的有效性优于氯吡格雷,但可增加出血发生率。     

P2Y12 receptor inhibitors for secondary prevention of ischemic stroke

Introduction: Ischemic stroke (IS) is a major cause of death and disability worldwide. The P2Y₁₂ receptor plays a critical role in the formation of a stable thrombus leading to ischemic complications. Therefore, P2Y₁₂ receptor inhibitors constitute a major antiplatelet strategy in the secondary prevention of IS.

Areas covered: We searched articles about P2Y₁₂ receptor inhibitors and stroke in PubMed published until December 2014. This is a comprehensive review of the role of P2Y₁₂ receptor inhibitors alone and in combination with aspirin in the secondary prevention of noncardioembolic stroke.

Expert opinion: The potential benefit of more potent antiplatelet therapy for secondary stroke prevention must be weighed against the risk of bleeding in patients with IS. Short-term (≤ 3 months) dual antiplatelet therapy with clopidogrel and aspirin that is initiated early after IS or transient ischemic attack due to large artery atherosclerosis appears most efficient.     

替格瑞洛在老年STEMI患者急诊PCI中的疗效与安全性分析

目的观察替格瑞洛在老年急性ST段抬高型心肌梗死(ST-segment elevated myocardial infarction,STEMI)患者急诊经皮冠状动脉介入治疗术(percutaneous coronary artery intervention,PCI)中的疗效和安全性。方法 2013年4月至2014年10月行急诊PCI术的60岁以上STEMI患者113例,采用数字表法随机分为负荷量替格瑞洛组(57例)和氯吡格雷组(56例),分别给予300 mg阿司匹林和180 mg替格瑞洛嚼服及300 mg阿司匹林和600 mg氯吡格雷嚼服。观察并比较2组患者急诊PCI术后无复流情况及术后1个月内主要心脏不良事件(major adverse cardiovascular events,MACE)发生率及出血、呼吸困难及恶性心律失常的发生率。结果替格瑞洛组无复流发生率以及术后1个月MACE的发生率均低于氯吡格雷组(P<0.05);而2组主要出血、恶性心律失常的发生率差异无统计学意义(P>0.05)。结论在老年STEMI患者的急诊PCI治疗中,应用替格瑞洛抗栓疗效显著,且安全性较好。     

氯吡格雷抵抗的临床处理

急性冠状动脉综合征的患者尽管接受了标准剂量的氯吡格雷治疗,仍有部分患者发生缺血性心血管事件,称为氯吡格雷抵抗。氯吡格雷抵抗引起的广泛关注使个体化抗血小板药物成为这些患者改善预后的治疗策略。在遗传学检测的辅助下,新型P2Y12受体拮抗剂普拉格雷、替卡格雷和坎格雷拉以及糖蛋白Ⅱb/Ⅲa受体拮抗剂和高剂量氯吡格雷是可能的应对措施。就现有的临床试验研究证据对氯吡格雷抵抗患者的个体化治疗做一综述。     

Effects of ticagrelor pretreatment on electrophysiological properties of stellate ganglion neurons following myocardial infarction

Higher sympathetic activity predisposes to malignant ventricular arrhythmias in the context of myocardial infarction (MI). This is, in part, mediated by the electrical activity of the stellate ganglion (SG). The aim of this study is to examine the effects of ticagrelor pretreatment on the electrophysiological properties of SG neurons following MI in rabbits. MI was induced by isoproterenol (ISO) of 150 mg kg^-1 d^-1 (twice at an interval of 24 hours). Ticagrelor pretreatment was administered at low- (10 mg kg^-1 d^-1) or high-dose (20 mg kg^-1 d^-1). Protein and RNA expression were determined by immunohistochemical analysis and real-time PCR, respectively. The activity of sodium channel current (I_Na), delayed rectifier potassium current (I_KDR), M-type potassium current (I_KM) as well as action potentials (APs) from SG neurons were measured by whole-cell patch-clamp. Intracellular calcium concentrations were measured by confocal microscopy. Compared with the control group, the MI group exhibited a greater amplitude of I_Na, I_KDR and I_KM, significantly altered activation and inactivation characteristics of I_Na, no significant alterations in protein or mRNA expression of sodium and M-type potassium channels, along with higher AP amplitude and frequency and intracellular calcium concentrations. Most of these abnormalities were prevented by pretreatment with low- or high-dose ticagrelor. Our data suggest that ticagrelor exerts cardioprotective effects, potentially through modulating the activity of different ion channels in SG neurons.     

替格瑞洛治疗急性冠状动脉综合征患者的临床研究

目的观察长期服用替格瑞洛对急性冠状动脉综合征患者的临床疗效及其对肌钙蛋白T(cTnT)、脑钠素(BNP)、C-反应蛋白(CRP)和D-二聚体(D-D)水平的影响。方法将84例急性冠状动脉综合征患者随机分为对照组42例和试验组42例。2组均给予常规治疗及对症治疗,术前服用阿司匹林150mg联合氯吡格雷300 mg,口服,每日1次,持续用药7 d,进行经皮冠状动脉介入(PCI)术。对照组术后服用阿司匹林100 mg,每日1次,连续服用6个月。试验组术后服用阿司匹林100 mg+替格瑞洛90 mg,每日1次,连续服用6个月。比较2组患者的临床疗效和急性心肌梗死发作次数、发作持续时、ST段下移水平、cTnT、BNP、CRP、D-D水平及药物不良反应发生情况。结果治疗后,对照组和试验组临床总有效率分别为78.57%(33例/42例)和95.24%(40例/42例),差异有统计学意义(P<0.05)。对照组和试验组治疗后急性心肌梗死发作次数分别为(4.52±0.55)和(2.02±0.27)次/周,发作持续时间分别为每次(4.14±0.43)和(2.76±0.31)min,ST段下移水平1.25±0.17和0.63±0.07,差异均有统计学意义(均P<0.05)。治疗后,对照组血清cTnT、BNP、CRP、D-D水平分别为(1.54±0.18)ng·mL^-1,(63.52±6.73)ng·mL^-1,(8.94±0.94)mg·mL^-1和(133.53±15.73)ng·mL^-1,试验组分别为(0.25±0.03)ng·mL^-1,(28.43±3.02)ng·mL^-1,(4.57±0.55)mg·mL^-1和(59.54±5.74)ng·mL^-1,差异均有统计学意义(均P<0.05)。对照组出现头痛2例,腹泻2例,恶心呕吐1例,眩晕2例,药物不良反应发生率为16.67%(7例/42例);试验组出现胃肠道出血1例,血肌酸酐轻度上升1例,眩晕1例,药物不良反应发生率为7.14%(3例/42例),2组差异无统计学意义(P>0.05)。结论长期服用替格瑞洛治疗急性冠状动脉综合征患者的临床疗效显著,安全性高。     

Ticagrelor for the prevention of ischemic events in patients with prior myocardial infarction and peripheral artery disease

Introduction: Cardiovascular disease (CVD) is the main cause of death in the world. Coronary artery disease (CAD) is the most common form of CVD presentation, but the prevalence of peripheral artery disease (PAD) is increasing. Patients with polyvascular disease comprise a very high-risk population that has been infrequently studied.

Areas covered: The authors review the current evidence of the efficacy and safety of ticagrelor in the setting of acute coronary syndrome and stable patients post-MI with and without PAD and summarize its pharmacokinetics, pharmacodynamics, and regulatory issues.

Expert opinion: Randomized studies showed that ticagrelor is superior to clopidogrel in patients with acute coronary syndromes, and is superior to placebo in the chronic phase (>1 year) post-myocardial infarction. Sub-analyses of these studies suggest that patients with myocardial infarction and PAD, compared to patients without these characteristics, may have greater benefit with ticagrelor. Nonetheless, the global evidence about the role of ticagrelor in patients with myocardial infarction and PAD remains relatively sparse, and a prospective randomized trial testing this hypothesis would be necessary to provide more definite data regarding the efficacy and safety of ticagrelor in this very high-risk population.