联合应用氯吡格雷和质子泵抑制剂对急性冠状动脉综合征患者经皮冠状动脉介入术后预后的影响

目的探讨联合应用氯吡格雷和质子泵抑制剂（PPI）对急性冠状动脉综合征（ACS）患者经皮冠状动脉介入（PCI）术后预后的影响。方法回顾性分析2003年至2014年来自10个国家（加拿大，巴西，德国，波兰，荷兰，西班牙，意大利，希腊，中国，日本）15个临床中心的ACS合并PCI术后18077例患者的临床资料。研究氯吡格雷、PPI与ACS患者PCI术后预后的关系。比较患者的基本临床特征、既往病史、生化指标、药物应用，以及终点事件的发生率情况。通过Cox回归模型进行分析及倾向性评分调整其他可能影响患者的预后因素包括人口学信息（年龄、性别）和临床指标，计算PPI这一干预因素的风险比并评价其是否能够明显影响患者的预后。结果基于国际多中心Blee MACs注册登记研究分析，排除关键数据缺失过多患者2676例。根据纳入与排除标准及倾向性评分调整整理后，再排除患者6461例，最终列队患者8940例。根据患者用药不同，将患者分为氯吡格雷＋PPI组（4814例）和氯吡格雷组（4126例）。氯吡格雷＋PPI组患者女性、高血压病史、高脂血症病史、糖尿病史、外周血管疾病史、既往急性心肌梗死史、慢性肾功能不全病史、消化道溃疡病史、冠状动脉旁路移植术病史、既往出血病史、恶性肿瘤病史、不稳定型心绞痛、非sT段抬高型心肌梗死、心功能Killip分级≥2级、经皮腔内冠状动脉成形术、出院后血管紧张素转换酶抑制剂／血管紧张素Ⅱ受体拮抗剂应用比例、年龄和入院时血肌酐水平明显高于氯吡格雷组[25．4％（1225／4814）比21．0％（865／4126）、59．9％（2882／4814）比49．2％（2032／4126）、48．3％（2327／4814）比42．7％（1762／4126）、26．4％（1272／4814）比22．1％（910／4126）、8．0％（386／4814）比5．6％（231／4126）、12．3％（593／4814）比10．6％（436／4126）、2．0％（98／4814）比0．7％（30／4126）、2．3％（112／4814）比1．0％（42／4126）、3．6％（172／4814）比2．2％（92／4126）、4．5％（219／4814）比3．0％（123／4126）、8．0％（387／4814）比4．7％（193／4126）、13．4％（644／4814）比9．1％（374／4126）、29．1％（1400／4814）比15．9％（656／4126）、14．5％（699／4814）比11．2％（462／4126）、56．0％（2697／4814）比55．7％（2300／4126）、75．5％（3633／4814）比68．6％（2829／4126）、（66±12）岁比（61±13）岁、（10±6）mg／L比（9±4）mg／L]；且入院时血红蛋白水平和出院后β受体阻滞剂应用比例明显低于氯吡格雷组[（138±19）g／L比（141±16）g／L、80．6％（3880／4814）比83．1％（3428／4126）]，差异均有统计学意义（均P〈0．05）。调整前，氯吡格雷＋PPI组主要终点事件（全因死亡／再发心肌梗死／出血）发生率明显高于氯吡格雷组，差异有统计学意义（风险比为1．331，95％置信区间为1．161-1．524）。调整后，氯吡格雷＋PPI组主要终点事件（全因死亡／再发心肌梗死／出血）发生率与氯吡格雷组比较，差异无统计学意义（风险比为1．036，95％置信区间为0．903-1．189）。结论ACS患者PCI术后联合应用PPI与氯吡格雷是合理的，尤其在胃肠道出血高危患者中。

Impact of concomitant use of proton pump inhibitors and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome

Background There is great debate on the possible adverse interaction between proton pump inhibitors （PPIs） and clopidogrel. In ad- dition, whether the use of PPIs affects the clinical efficacy of ticagrelor remains less known. We aimed to determine the impact of concomi- tant administration of PPIs and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome （ACS） after percuta- neous coronary intervention （PCI）. Methods We retrospectively analyzed data fi＇om a ＂real world＂, international, multi-center registry between 2003 and 2014 （n = 15,401） and assessed the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year composite primary endpoint （all-cause death, re-infarction, or severe bleeding） in patients with ACS after PCI. Results Of 9429 patients in the final cohort, 54.8% （n = 5165） was prescribed a PPI at discharge. Patients receiving a PPI were older, more often female, and were more likely to have comorbidities. No association was observed between PPI use and the primary endpoint for patients receiving clopidogrel （ad- justed HR： 1.036; 95% CI： 0.903-1.189） or ticagrelor （adjusted HR： 2.320; 95% CI： 0.875-45.151） （Pinteraction = 0.2004）. Similarly, use of a PPI was not associated with increased risk of all-cause death, re-infarction, or a decreased risk of severe bleeding for patients treated with either clopidogrel or ticagrelor. Conclusions In patients with ACS following PCI, concomitant use of PPIs was not associated with in- creased risk of adverse outcomes in patients receiving either clopidogrel or ticagrelor. Our findings indicate it is reasonable to use a PPI in combination with clopidogrel or ticagrelor, especially in patients with a higher risk of gastrointestinal bleeding.

Impact of triple antithrombotic therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention in real-world practice

Objective The optimal antithrombotic regimen for patients on oral anticoagulation （OAC） after acute coronary syndrome （ACS） and percutaneous coronary intervention （PCI） remains debated. This study sought to evaluate the efficacy and safety of OAC plus clopidogrel with or without aspirin in a real-world setting. Methods We retrospectively analyzed data from an international, multi-center registry be- tween 2003 and 2014 （n = 15,401）. Patients with ACS and receiving OAC after PCI were screened. The composite primary endpoint was 1-year all-cause death, re-infarction, or severe bleeding. Results The final analysis enrolled 642 patients including 62 patients （9.7%） with OAC and clopidogrel （dual therapy）, and 580 patients （90.3%） with the combination of aspirin, OAC and clopidogrel （triple therapy）. Pa- tients on triple therapy were more often female and were more likely to have comorbidities. There was no significant difference regarding the primary end point between dual therapy with triple therapy patients [17.74% vs. 17.24%; unadjusted hazard ratio （HR）： 1.035; 95% confi- dence interval （CI）： 0.556-1.929; adjusted HR： 1.026; 95% CI： 0.544-1.937]. However, the re-infarction rate was significantly higher in dual therapy than triple therapy patients （14.52% vs. 5.34%; unadjusted HR： 2.807; 95% CI： 1.329-5.928; adjusted HR： 2.333; 95% CI： 1.078-5.047）. In addition, there was no difference between two regimes in all-cause death and severe bleeding. Conclusions In real-life patients with ACS following PCI and with an indication of OAC, triple therapy was not associated with an increased rate of adverse out- comes compared to dual therapy. Moreover, it decreased risk of re-infarction and did not increase risk of severe bleeding.

Coronary atherosclerosis burden is not advanced in patients with β-thalassemia despite premature extracardiac atherosclerosis： a coronary artery calcium score and carotid intima-media thickness study

Background Thalassemic patients demonstrate an increased rate of extracardiae vascular complications and increased carotid wall intima-media thickness （cIMT）, but very low prevalence of coronary artery disease （CAD）. We investigated the atheroma burden by assessing the coronary artery calcium （CAC） and elMT in these patients. Methods We examined 37 patients with β-thalassemia and 150 healthy control volunteers with multi-detector computer tomography （CT） and ultrasonography to determine CAC score and cIMT, respectively. Results Propensity score matching （C-statistic： 0.88; 95% CI： 0.83-0.93） resulted in 27 pairs of patients; severe CAC was observed in 2 （7.4%） and 0 of β-thalassemia patients and healthy volunteers respectively （P = 0.5）. Median calcium score was 0 （0-0） in β-thalassemia patients and 0 （0-4） in healthy volunteers （P = 0.8）. Median intima-media thickness was higher in β-thalassemia patients compared to control group [0.45 （0.06-0.65） vs. 0.062 （0.054-0.086）; P = 0.04]. Conclusions Patients with β-thalassemia in comparison with healthy control subjects exhibit similar CAC score and increased cIMT. Our findings indicate a disparate rate of progression of atherosclerosis between coronary and extracardiac arteries in these patients lending support to the epidemiological evidence.

P2Y12受体抑制剂联合质子泵抑制剂对急性冠脉综合征患者缺血事件影响的临床分析

目的本研究旨在分析P2Y12受体抑制剂联合质子泵抑制剂（PPI）治疗对经皮冠状动脉介入（PCI）术后的急性冠脉综合征患者缺血事件的影响。方法基于国际多中心回顾性注册登记研究，纳入2003至2014年因急性冠脉综合征人院行PCI术的患者，分为PPI组及非PPI组并随访1年，主要临床终点为全因死亡／再发心肌梗死的复合终点。根据P2Y12受体抑制剂种类，将入组患者分为氯吡格雷组及替格瑞洛组，并比较不同药物与PPI联用发生临床终点事件的风险。结果研究入选9429例患者，PPI组占54．8％，具有更多高危因素。Cox回归结果提示PPI组较非PPI组全因死亡／再发心肌梗死复合事件的发生差异无统计学意义（HR1．00，95％CI 0．86—1．18）。根据P2Y12抑制剂种类不同分为氯吡格雷组和替格瑞洛组，不同P2Y12受体抑制剂联用PPI较未联用PPI患者的临床终点无差异，联用PPI的氯吡格雷组与替格瑞洛组的临床终点差异也无统计学意义。结论急性冠脉综合征患者PPI与P2Y12受体抑制剂联用不增加全因死亡和再发心肌梗死风险，尤其PPI联用氯吡格雷在患者的缺血事件上与替格瑞洛比较差异无统计学意义。