Usefulness of the PARIS Score to Evaluate the Ischemic-hemorrhagic Net Benefit With Ticagrelor and Prasugrel After an Acute Coronary Syndrome

Introduction and objectives

The PARIS score allows combined stratification of ischemic and hemorrhagic risk in patients with ischemic heart disease treated with coronary stenting and dual antiplatelet therapy (DAPT). Its usefulness in patients with acute coronary syndrome (ACS) treated with ticagrelor or prasugrel is unknown. We investigated this issue in an international registry.

替格瑞洛对急性冠状动脉综合征患者血小板聚集的影响

目的比较替格瑞洛和氯吡格雷对急性冠状动脉综合征(ACS)患者血小板聚集的影响。方法 81例ACS患者被随机分为替格瑞洛组(A组,41例)和氯吡格雷组(B组,40例),比较两组服药前和服药后1、2、4、8、24h及治疗第7天的血小板最大聚集率(PMAR)、血小板聚集抑制率(IPA)及出血事件。结果两组服药前PMAR水平相近(P>0.05)。A组患者服药期间的PMAR均低于B组(P<0.01),IPA及IPA≥50%的患者比例均高于B组(P<0.01)。B组服药后2h的IPA低于服药后8h(P<0.01),而A组两个时间段IPA差异无统计学意义(P>0.05)。两组均只有轻微出血事件。结论在ACS患者,替格瑞洛较氯吡格雷更能有效地抑制血小板聚集;两药短期的安全性相仿。     

Diabetes-Related Factors and the Effects of Ticagrelor Plus Aspirin in the THEMIS and THEMIS-PCI Trials

BackgroundTHEMIS (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study) (n = 19,220) and its pre-specified THEMIS-PCI (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study-Percutaneous Coronary Intervention) (n = 11,154) subanalysis showed, in individuals with type 2 diabetes mellitus (median duration 10.0 years; HbA_1c 7.1%) and stable coronary artery disease without prior myocardial infarction (MI) or stroke, that ticagrelor plus aspirin (compared with placebo plus aspirin) produced a favorable net clinical benefit (composite of all-cause mortality, MI, stroke, fatal bleeding, and intracranial bleeding) if the patients had a previous percutaneous coronary intervention.ObjectivesIn these post hoc analyses, the authors examined whether the primary efficacy outcome (cardiovascular death, MI, stroke: 3-point major adverse cardiovascular events [MACE]), primary safety outcome (Thrombolysis In Myocardial Infarction–defined major bleeding) and net clinical benefit varied with diabetes-related factors.MethodsOutcomes were analyzed across baseline diabetes duration, HbA_1c, and antihyperglycemic medications.ResultsIn THEMIS, the incidence of 3-point MACE increased with diabetes duration (6.7% for ≤5 years, 11.1% for >20 years) and HbA_1c (6.4% for ≤6.0%, 11.8% for >10.0%). The relative benefits of ticagrelor plus aspirin on 3-point MACE reduction (hazard ratio [HR]: 0.90; p = 0.04) were generally consistent across subgroups. Major bleeding event rate (overall: 1.6%) did not vary by diabetes duration or HbA_1c and was increased similarly by ticagrelor across all subgroups (HR: 2.32; p < 0.001). These findings were mirrored in THEMIS-PCI. The efficacy and safety of ticagrelor plus aspirin did not differ by baseline antihyperglycemic therapy. In THEMIS-PCI, but not THEMIS, ticagrelor generally produced favorable net clinical benefit across diabetes duration, HbA_1c, and antihyperglycemic medications.ConclusionTicagrelor plus aspirin yielded generally consistent and favorable net clinical benefit across the diabetes-related factors in THEMIS-PCI but not in the overall THEMIS population.     

替格瑞洛对急性冠状动脉综合征患者经皮冠状动脉介入治疗后QT离散度及高敏C反应蛋白与可溶性CD40配体的影响

目的 探讨替格瑞洛对急性冠状动脉综合征(ACS)患者在经皮冠状动脉介入治疗(PCI)后QT离散度(QTd)以及对炎性因子高敏C反应蛋白(hs-CRP)、可溶性CD40配体(sCD40L)的影响.方法 抽取本院2017年1~12月接受PCI的ACS患者69例,随机分为对照组34例(口服氯吡格雷)、试验组35例(口服替格瑞洛),两组均使用阿司匹林行双联抗血小板聚集(DAPT)治疗1年.测量两组治疗前及术后24 h、1个月、1年QTd值以及静脉血hs-CRP、sCD40L值.术后6个月随访恶性心律失常的发生情况.结果 术后24 h,试验组QTd值及hs-CRP、sCD40L水平均低于对照组[(42.66±4.32)比(46.61±4.86),(3.73±0.39)mg/L比(4.06±0.42)mg/L,(593.94±61.69)ng/ml比(640.35±66.21)ng/ml](P<0.05);术后1个月,试验组QTd值及hs-CRP、sCD40L水平均低于对照组[(37.86±3.89)比(41.00±4.32),(1.87±0.21)mg/L比(2.03±0.22)mg/L,(417.20±43.21)ng/ml比(457.15±48.25)ng/ml](P<0.05);术后1年,试验组QTd值及hs-CRP、sCD40L水平均低于对照组[(32.19±3.35)比(37.36±3.81),(1.41±0.16)mg/L比(1.69±0.18)mg/L,(336.28±3.56)ng/ml比(387.96±3.91)ng/ml](P<0.05).术后6个月内,试验组恶性心律失常发生率(22.9%)小于对照组(47.1%)(P<0.05).结论 ACS患者PCI围术期应用替格瑞洛能显著缩短QTd,降低炎性因子hs-CRP、sCD40L水平,降低恶性心律失常发生率,显著改善预后.     

阿司匹林联合替格瑞洛或氯吡格雷对急性冠状动脉综合征患者高尿酸血症发生率影响的对比研究

目的 比较阿司匹林联合替格瑞洛或氯吡格雷对急性冠状动脉综合征(ACS)患者高尿酸血症发生率的影响.方法 选取2018年2~12月在中国医科大学盛京医院心内科住院的ACS患者476例.根据经皮冠状动脉介入治疗(PCI)术后患者应用抗血小板方案不同分为阿司匹林100 mg/d联合氯吡格雷75 mg/d组243例,阿司匹林100 mg/d联合替格瑞洛90 mg/bid组233例;以两组患者术前血尿酸值为基础对照,观察两组患者用药7天、1个月、3个月、6个月时的血尿酸水平及高尿酸血症发生率.结果 两组患者在性别、年龄等方面比较差异均无统计学意义(P>0.05).两组患者用药前血尿酸水平差异无统计学意义(P=0.238),用药1个月、3个月、6个月时,替格瑞洛组高尿酸血症发生率高于氯吡格雷组,差异有统计学意义(χ2值分别为7.623、20.367、14.018,P<0.05);多因素Logistic回归分析显示,在调整了混杂因素后,口服替格瑞洛与口服氯吡格雷对ACS患者高尿酸血症发生率影响仍有差异(β=-1.139,SE=0.249,Waldχ2=20.903,OR=0.320,95%CI 0.196~0.522);重复测量设计分析显示两组患者的血尿酸水平随着用药时间变化的趋势不同,用药组别与用药时间之间存在交互作用(F=6.201,P<0.05).结论 替格瑞洛组较氯吡格雷组对ACS患者血尿酸水平影响更大,导致高尿酸血症发生率更高,在用药3个月时血尿酸水平达高峰,需要临床医师重视血尿酸管理,建议患者至少要在用药1个月及3个月时复查血尿酸水平,便于及时调整用药与早期干预.     

Antiplatelet therapy in patients after an acute coronary syndrome: Comparison of the Czech and Slovak Republics Results of the ATHRO registry

BackgroundThe modern treatment of acute coronary syndromes includes early initiation of dual antiplatelet therapy (DAPT) and coronary angiography (CAG) followed by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Recently two new potent antiplatelet agents (ticagrelor and prasugrel) were introduced in clinical practice. The aim of this registry was to analyze the treatment strategies in two neighboring countries: Czech (CZ) and Slovak (SK) Republics.Patients and methodsA total of 1541 patients was enrolled during one month period in 18 tertiary cardiac centers in CZ (n = 1026) and 6 centers in SK (n = 515). The mean age was 66 ± 12 years (CZ) vs. 63 ± 12 (SK), diabetes mellitus was present in 31.1% (CZ) and 32.6% (SK). Prior revascularization was reported in 21.9% (CZ) vs. 16.1% (SK).ResultsST-segment elevation myocardial infarction (STEMI) was the final diagnosis in 51.9% (CZ) vs. 44.9% (SK), non-STEMI in 34.1% vs. 31.3% and unstable angina pectoris (UAP) in 14.0% vs. 23.9%. PCI during the initial hospital stay was performed in 83.4% (CZ) vs. 78.8% (SK). The discharge medication included aspirin in 95.3% (both countries), clopidogrel in 75.3% (CZ) vs. 53.6% (SK), ticagrelor in 13.1% (CZ) vs. 17.3% (SK) and prasugrel in 2.6% (CZ) vs. 23.1% (SK). Economic limits were reported to influence the choice of P2Y12 inhibitor in 36.9% (CZ) vs. 23.9% (SK).The indication for ticagrelor was in STEMI 73.9% (CZ) vs. 36.0% (SK), non-STEMI in 20.9% (CZ) vs. 40.4% (SK) and UAP in 5.2% (CZ) vs. 23.6% (SK). The indication for prasugrel was STEMI in 81.5% (CZ) vs. 73.9% (SK), non-STEMI in 18.5% (CZ) vs. 11.8% (SK) and UAP in 0.0% (CZ) vs. 14.3% (SK).ConclusionsThe baseline characteristics of ACS patients are similar in both countries, and the Czech patients tend to be older and have more prior revascularizations. Slovak patients receive more often modern potent P2Y12 inhibitors. The results confirm existing economic barriers preventing full implementation of the antiplatelet recommendations from the current ESC guidelines, but also lack of guidelines knowledge (or implementation) among some physicians.     

替格瑞洛、氯吡格雷对急性冠脉综合征患者PCI术后血小板聚集率、血流动力学及免疫功能的影响

目的:探讨替格瑞洛、氯吡格雷对急性冠脉综合征（ACS）患者经皮冠状动脉介入治疗（PCI）术后血小板聚集率、血流动力学及免疫功能的影响。方法:选取本院心血管内科收治的124例ACS患者作为研究对象,随机分为观察组（n=62）和对照组（n =62）,观察组给予替格瑞洛治疗,对照组给予氯吡格雷治疗,观察比较两组患者治疗前后小板聚集率、血流动力学指标、免疫功能指标变化情况和出血情况。结果:治疗后,两组患者血小板聚集率（PAV）均低于治疗前（P＜0.05）,且观察组明显低于对照组（P＜0.05）;治疗后,两组患者全血黏度（BV）、血浆粘度（PV）均低于治疗前（P＜0.05）,观察组明显低于对照组（P＜0.05）,而收缩期血流速度峰值（SPV）,舒张期血流速度峰值（DPV）,冠脉血流储备（CFVR）均高于治疗前（P＜0.05）,且观察组明显高于对照组（P＜0.05）;治疗后,两组患者CD3+、CD4+水平均高于治疗前（P＜0.05）,观察组明显高于对照组（P＜0.05）,而CD8+水平低于治疗前（P＜0.05）,观察组低于对照组（P＜0.05）;两组患者总出血事件发生率比较差异无统计学意义（P＞0.05）。结论:替格瑞洛能有效抑制ACS患者PCI术后血小板凝集,改善血流动力学和免疫功能,安全性高。     

Impact of point-of-care testing for CYP2C19 on platelet inhibition in patients with acute coronary syndrome and early dual antiplatelet therapy in the emergency setting

Aims

Only limited data exist about the role of point of care CYP2C19 testing in the acute setting in the early phase of acute coronary syndromes (ACS). Therefore, the present study was designed to investigate the impact of CYP2C19 loss-of–function point-of-care (POC) genotyping in patients presenting with acute coronary syndromes (ACS) and treated with dual antiplatelet therapy in the emergency setting.

Methods and Results

137 subjects with ACS scheduled for percutaneous coronary intervention were consecutively enrolled. Pre- and on-treatment platelet aggregation was assessed by multiple electrode aggregometry (MEA) after stimulation with adenosine diphosphate (ADP). Patients were loaded according to current guideline adherent indications and contraindications for use of P2Y₁₂ inhibitors in ACS. POC genotyping for CYP2C19*2 was performed in the emergency room after obtaining a buccal swab using the Spartan RX CYP2C19 system and obtaining patient’s informed consent. Prasugrel and ticagrelor treated patients had significantly lower PR compared to clopidogrel-treated patients. The benefits of prasugrel and ticagrelor compared to clopidogrel treated patients in terms of platelet inhibition were more pronounced in CYP2C19*2 carriers. Non-carriers showed similar inhibition regardless of particular P2Y₁₂ inhibitor treatment. Statistical analyses adjusting for factors associated with response (e.g. smoking) revealed that CYP2C19*2 allele carrier status and loading with different type of P2Y12 receptor blockers were significant predictors of on-treatment platelet reactivity in the early phase of ACS.

Conclusion

The results of this pilot study of treatment of patients in the early phase of ACS indicate that CYP2C19*2 POC genotyping might help to identify patients at risk with poor response to clopidogrel treatment, thereby benefiting from reloading and switching to alternative P2Y₁₂ receptor inhibition.     

服用氯吡格雷或替格瑞洛患者的血小板最大聚集率差异研究

摘 要 目的：研究经皮冠脉介入术（PCI）后服用氯吡格雷的患者与服用替格瑞洛的患者血小板最大聚集率（MAR）的差异和出血情况,为临床使用抗血小板药物提供参考。方法: 选取因急性冠状动脉综合征(ACS)入院行PCI后服用氯吡格雷或者替格瑞洛的患者,在出院前对其MAR值进行检测,随访3个月内出血事件的发生情况,并比较两组患者MAR值以及随访结果的差异。结果: 服用氯吡格雷的患者出院时MAR为（51.1±13.7）%（n=76）,服用替格瑞洛的患者MAR为（32.6±15.7）%（n=76）,两组差异有统计学意义（P<0.001）。随访结果显示氯吡格雷组出血事件低于替格瑞洛组（P<0.05）。结论: 服用替格瑞洛的患者出院后出血的倾向可能比服用氯吡格雷的患者更大。     

替格瑞洛停药时间对非停跳冠脉搭桥的风险影响

目的：将口服替格瑞洛的急性冠脉综合征需要急诊冠脉搭桥的患者与同期择期冠脉搭桥围手术期相关指标进行比较,总结该类患者急诊手术围手术期风险。方法：回顾分析2016年1月至2019年12月在我科接受急诊冠脉搭桥（n=36,术前停服替格瑞洛小于48小时）和择期冠脉搭桥（n=346,术前停服替格瑞洛大于5天）的急性冠脉综合征382例患者,比较两组患者围手术期相关数据。结果：两组患者术前基线资料及手术时间、手术搭桥数目无显著差别;术后住院期间死亡率急诊组明显高于择期组;另外术后呼吸机辅助时间、ICU居住时间、二次开胸止血发生率、术后24小时引流量、以及术后输血量上急诊组明显高于对照组。结论：停服替格瑞洛48小时以内接受急诊冠脉搭桥患者围手术期风险高于停药时间大于5天的择期组患者。