何鹏义,木胡牙提·乌拉斯汉,赵燕,王珊珊,杨玉春,刘志强,张雷,巧丽盼,摆玲,潘光巍

• 1:新疆医科大学第一附属医院综合心脏内科

摘要(Abstract)：

目的研究急性ST段抬高心肌梗死(STEMI)行直接经皮冠状动脉介入治疗(PCI)患者围术期使用比伐卢定或肝素联合替罗非班对患者血栓、出血发生情况及P-选择素水平的影响。方法纳入STEMI患者260例,按随机法分为比伐卢定组(129例)和肝素+替罗非班组(131例),分别在PCI术前(用药之前)、术中(用药20 min左右)、术后(手术结束后3 h)采取静脉血,检测血清P-选择素水平。观察30 d内出血、血小板减少症和支架内血栓形成事件的预后评估。结果肝素+替罗非班组患者用药后P-选择素水平先逐渐升高,随时间延长逐渐下降,因而P-选择素水平术中、术后显著大于术前,差异均有统计学意义(均P<0.05)。比伐卢定组患者用药后,P-选择素水平明显下降,用药后维持在较低水平,停药后回升,因而P-选择素水平术中、术后均显著低于术前,差异均有统计学意义(均P<0.05);而术中与术后相比,差异无统计学意义(P>0.05)。两组患者术前P-选择素水平比较,差异无统计学意义(P=0.863),比伐卢定组P-选择素水平术中-术前的差值[(-2.1279±4.81552)pg/ml比(2.5238±6.96788)pg/ml,P<0.001]、术后-术前的差值[(-1.1692±4.43138)pg/ml比(0.9748±6.20749)pg/ml,P=0.006]均显著低于肝素+替罗非班组,差异均有统计学意义。随访30 d,比伐卢定组患者美国出血学术研究会出血标准(BRAC)2~5型发生率(0.8%比5.3%,P=0.029)显著低于肝素+替罗非班组,差异有统计学意义。两组患者BRAC3~5型出血、获得性血小板减少症、24 h急性血栓和30 d亚急性血栓发生率比较,差异均无统计学意义(均P>0.05)。结论比伐卢定可以在短期内降低STEMI患者直接PCI围术期P-选择素水平,而肝素则升高围术期P-选择素水平;比伐卢定可以降低BRAC2~5型出血发生率。

关键词(KeyWords)： 比伐卢定;肝素;P-选择素;ST段抬高心肌梗死;经皮冠状动脉介入治疗

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 何鹏义,木胡牙提·乌拉斯汉,赵燕,王珊珊,杨玉春,刘志强,张雷,巧丽盼,摆玲,潘光巍

参考文献(References)：

• [1]Amsterdam EA,Wenger NK,Brindis RG,et al.2014 AHA/ACC Guideline for the management of patients with non-ST-elevation acute coronary syndromes:a report of the American College of Cardiology/American Heart Association task forceon practice guidelines.J Am Coll Cardiol,2014,64(24):e139-e228.
• [2]Steg PG,James SK,Atar D,et al.ESC Guidelines for the management of acute myocardial infarction inpatients presenting with ST-segment elevation.Eur Heart J,2012,33(20):2569-2619.
• [3]O'Gara PT,Kushner FG,Ascheim DD,et al.2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction:executive summary:a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines:developed in collaboration with the American College of Emergency Physicians and Society for Cardiovascular Angiogranphy and Interventions.Catheter Cardiovasc Interv,2013,82(1):E1-E27.
• [4]Windecker S,Kolh P,Alfonso F,et al.2014 ESC/EACTS Guidelines on myocardial revascularization:the task force on myocardial revascularization of the European Society of Cardiology(ESC)and the Europan Association for Cardio-Thoracic Surgery(EACTS)developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions(EAPCI).Eur Heart J,2014,35(37):2541-2619.
• [5]Mehran R,Rao SV,Bhatt DL,et al.Standardized bleeding definitions for cardiovascular clinical trials:a consensus report from the Bleeding Academic Research Consortium.Circulation,2011,123(23):2736-2747.
• [6]Cutlip DE,Windecker S,Mehran R,et al.Clinical end points in coronary stent trials:a case for standardized definitions.Circulation,2007,115(17):2344-2351.
• [7]Khismatullin DB,Truskey GA.Leukocyte rolling on P-selectin:a three dimensional numerical study of the effect of cytoplasmic viscosity.Biophys J,2012,102(8):1757-1766.
• [8]Ross R.The pathogenesis of atherosclerosis:a perspective for1990s.Nature,1993,362(6423):801-809.
• [9]李金怀,韩斌,杨文东.冠心病患者血清脂联素和P-选择素水平变化及其检测价值.临床医学,2011,31(4):99-100.
• [10]Liu J,Dong W,Quan X,et al.Transgenic expression of human Pselectin glycoprotein ligand-1 is not sufficient for enterovirus 71infection in mice.Arch Virol,2012,157(3):539-543.
• [11]Yamaoka T,Fujimoto M,Ogawa F,et al.The roles of P-and Eselectins and P-selectin glycoprotein ligand-1 in primary and metastatic mouse melanomas.J Dermatol Sci,2011,64(2):99-107.
• [12]潘莹.血小板P选择素与动脉粥样硬化研究进展.安徽医科大学学报,2012,47(10):1237-1240.
• [13]马彩云,柳景华,马芹,等.冠心病与血管内皮细胞标志物关系的研究.中国介入心脏病学杂志,2016,24(2):104-106.
• [14]孟晓军,王晓燕.急性冠脉综合征合并糖尿病患者冠脉病变严重程度与P-选择素水平变化的临床观察研究.中国慢性病预防与控制,2011,19(3):273-274.
• [15]Kimmelstiel C,Zhang P,Kapur NK,et al.Bivalirudin is a dual inhibitor of thrombin and collagen-dependent platelet activation in patients undergoing percutaneous coronary intervention.Circ Cardiovasc Interv,2011,4(2):171-179.
• [16]Eslam RB,Reiter N,Kaider A,et al.Regulation of PAR-1 in patients undergoing percutaneous coronary intervention:effects of unfractionated heparin and bivalirudin.Eur Heart J,2009,30(15);1831-1836.
• [17]Warkentint,Greinacher A,Koster A.Bivalirudin.Thromb Haemost,2008,99:830-839.
• [18]Han Y,Guo J,Zheng Y,et al.Bivalirudin vs heparin with or without tirofiban during primary percutaneous coronary intervention in acute myocardial infarction:the BRIGHT randomized clinical trial.JAMA,2015,313(13):1336-1346.
• [19]Gao C,Boylan B,Fang J,et al.Heparin promotes platelet responsiveness by potentiatingαIIbβ-mediated outside-in signaling.Blood,2011,117(18):4946-4952.
• [20]Montalescot G,Wiviott SD,Braunwald E,et al.Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction(TRITON-TIMI 38):double-blind,randomised controlled trial.Lancet,2009,373(9665):723-731.
• [21]Storey RF,May JA,Heptinstall S.Potentiation of platelet aggregation by hepafin in human whole blood is attenuated by P2Y12 and P2Y1 antagonists but not aspirin.Thromb Res,2005,115(4):301-307.
• [22]Day JR,Malik IS,Weerasinghe A,et al.Distinct yet complementary mechanisms of heparin and glycoprotein IIb/III a inhibitors on platelat activation and aggregation:implications for restenosis during percutaneous coronary intervention.Heart,2004,90(7):794-799.
• [23]Massberg S,Mueller I,Besta F,et al.Effects of 2 different antiplatelet regimens with abciximab or tirofiban on platelet function in patients undergoing coronary stenting.Am Heart J,2003,146(5):E19.
• [24]谢双锋,尹松梅,聂大年,等.替罗非班在体外对P-选择素、白介素-6、白介素-1β的影响.中国临床药理学与治疗学,2010,15(7):732-736.
• [25]Stone GW,Witzenbichler B,Guagliumi G,et al.Bivalirudin during primary PCI in acute myocardial infarction.N Engl J Med,2008,358(21):2218-2230.
• [26]Stone GW,Witzenbichler B,Guagliumi G,et al.Heparin plus a glycoprotein IIb/IIIa inhibitor versus bivalirudin monotherapy and paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction(HORIZONS-AMI):final 3-year results from a multicentre,randomised controlled trial.Lancet,2011,377(9784):2193-2204.
• [27]Sibbing D,Busch G,Braun S,et al.Impact of bivalirudin or unfractionated heparin on platelet aggregation in patients pretreated with 600 mg clopidogrel undergoing elective percutaneous coronary intervention.Eur Heart J,2008,29(12):1504-1509.
• [28]Bates SM,Weitz JI.Direct thrombin inhibitors for treatment of arterial thrombosis:potential differences between bivalirudin and hirudin.Am J Cardiol,1998,82(8B):12P-18P.
• [29]Ndrepepa G,Schuster T,Hadamitzky M,et al.Validation of the Bleeding Academic Research Consortium definition of bleeding in patients with coronary artery disease undergoing percutaneous coronary intervention.Circulation,2012,125(11):1424-1431.
• [30]Yoon YH,Kim YH,Kim SO,et al.Impact of in-hospital bleeding according to the Bleeding Academic Research consortium classification on the long-term adverse outcomes in patients undergoing percutaneous coronary intervention.Catheter Cardiovasc Interv,2015,85(1):63-71.