急性冠状动脉综合征患者经皮冠状动脉介入术后出血情况分析

目的分析急性冠状动脉综合征（ACS）经皮冠状动脉介入（PCI）术后出血情况。方法回顾性分析2003年1月至2014年12月来自11个国家16个临床中心的18077例行PCI的ACS患者的临床资料。根据是否出现出血事件，将患者分为出血组（558例）和非出血组（17519例），比较2组患者的基本临床特征、手术情况及生化指标。分析ACS患者PCI术后出血相关情况。结果马其顿中心数据因关键变量缺失过多而被排除患者2676例，故最终纳入10个国家15个中心15401例ACS患者。排除缺失数据，本研究共有12910例患者收集到出血部位的数据，409例患者存在出血事件。胃肠道是最常见出血部位，占48．7％（199／409），颅内出血占7．6％（31／409）。Logistic逐步回归方法多因素分析显示，既往出血病史、高血压病史是术后1年内消化道出血的危险因素。排除马其顿中心数据（2676例）与Cox回归模型和倾向性评分调整再排除5972例，剩余9429例作分层分析。根据是否联用质子泵抑制剂（PPI），将出院应用氯吡格雷生存患者8942例分为氯吡格雷联合应用PPI组（4814例）和氯吡格雷未联合应用PPI组（4126例）；将出院应用替格瑞洛生存患者489例分为替格瑞洛联合应用PPI组（351例）和替格瑞洛未联合应用PPI组（138例）。Kaplan-Meier法分析显示氯吡格雷联合应用PPI组1年出血事件发生率明显高于氯吡格雷未联合应用PPI组，差异有统计学意义（P=0．004）；替格瑞洛联合应用PPI组1年出血事件发生率与替格瑞洛未联合应用PPI组比较，差异无统计学意义（P=0．573）。结论ACS患者PCI术后最常见的出血部位为消化道，PPI与替格瑞洛联合应用在胃肠道出血风险较高患者中适用。

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.

Bleeding risk assessment in elderly patients with acute coronary syndrome

Nowadays,elderly people represent a growing population segment with a well known increased risk of both ischemic and bleeding events.Current acute coronary syndrome guidelines,strongly recommend dual antiplatelet therapy(DAPT)with few specific references for aged patients due to lack of evidence.Patients aged>75 years are misrepresented in the classic derivation trials cohorts.Strategies to reduce the bleeding risk in this group of patients are urgently needed for the daily clinical practice.Identify the specific age related bleeding risk factors and the importance of an integral geriatric assessment remains challenging.Some of the available in-hospital and out-hospital bleeding risk scores have shown a lower to moderate predictive ability in older patients and no specific tools are developed in elderly population.The importance of an appropriate vascular access choice,type and duration of antiplatelet drugs is crucial to reduce the bleeding risk.Increase radial approaches and short DAPT duration leads to reduce hemorrhages.One interesting subgroup of patients is those who need chronic anticoagulation therapy after percutaneous coronary intervention,due to their very high risk of bleeding.New alternatives as dual therapy with oral anticoagulation and only one antiplatlet drug should be considered.In current review,we evaluate the available evidence about bleeding risk in elderly.

Renal function assessment in atrial fibrillation:Usefulness of chronic kidney disease epidemiology collaboration vs reexpressed 4 variable modification of diet in renal disease

AIM: To compare the performance of the re-expressed Modification of Diet in Renal Disease equation vs the new Chronic Kidney Disease Epidemiology Collaboration equation in patients with non-valvular atrial fibrillation.METHODS: We studied 911 consecutive patients with non-valvular atrial fibrillation on vitamin-K antagonist. The performance of the re-expressed Modification of Diet in Renal Disease equation vs the new Chronic Kidney Disease Epidemiology Collaboration equation in patients with non-valvular atrial fibrillation with respect to either a composite endpoint of major bleeding, thromboembolic events and all-cause mortality or each individual component of the composite endpoint was assessed using continuous and categorical ≥ 60, 59-30, and < 30 m L/min per 1.73 m2 estimated glomerular filtration rate.RESULTS: During 10 ± 3 mo, the composite endpoint occurred in 98(10.8%) patients: 30 patients developed major bleeding, 18 had thromboembolic events, and 60 died. The new equation provided lower prevalence of renal dysfunction < 60 m L/min per 1.73 m2(32.9%),compared with the re-expressed equation(34.1%). Estimated glomerular filtration rate from both equations was independent predictor of composite endpoint(HR = 0.98 and 0.97 for the re-expressed and the new equation, respectively; P < 0.0001) and all-cause mortality(HR = 0.98 for both equations, P < 0.01). Strong association with thromboembolic events was observed only when estimated glomerular filtration rate was < 30 m L/min per 1.73 m2: HR is 5.1 for the re-expressed equation, and HR = 5.0 for the new equation. No significant association with major bleeding was observed for both equations.CONCLUSION: The new equation reduced the prevalence of renal dysfunction. Both equations performed similarly in predicting major adverse outcomes.

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。