摘要
目的:回顾性分析急性冠脉综合征(ACS)患者植入药物洗脱支架(DES)后.30天内支架内血栓(ST)和主要不良心脏事件(MACE)的发生率,探究三联抗血小板(小剂量替罗非班加阿司匹林和氯吡格雷)较双联抗血小板(阿司匹林和氯吡咯雷)对预防ACS患者PCI术后30天内ST和MACE(心源性死亡、心肌梗死和紧急靶血管血.运重建)的有效性和安全性。而后,筛选年龄≥60岁的老年ACS患者,根据同样的分组及用药方法,探究三联抗血小板较双联抗血小板对预防老年ACS患者PCI术后30天内ST和MACE的有效性和安全性。
方法:采集2004年3月到2010年11月因ACS就诊于我院并植入DES的患者2904例,部分患者采用双联抗血小板治疗(双联组,n=1145),部分患者采用三联抗血小板治疗(三联组,n=1759),比较两组患者PCI术后30天内ST、MACE及临床不良反应的发生率。筛选年龄≥60岁的1629例老年ACS患者并分为三联组(n=1040例)和双联组(n=589例),比较两组老年ACS患者PCI术后30天内ST. MACE及临床不良反应的发生率。
结果:a.ACS患者:(1)虽然两组间患者的年龄,病变狭窄程度,吸烟、糖尿病、高脂血症和冠状动脉弥漫性病变的比率有差异,但通过cox分析发现以上因索对终点事件的发生无影响,两组患者其余基线资料基本一致。(2)三联组主要终点事件ST的发生率低于双联组(0.11%vs.1.05%,HR:0.108,95%CI:0.024-0.483,P=0.0036),三联组较双联组相对风险降低89.52%。三联组次要终点事件MACE的发生率也低于双联组(0.17%vs.1.48%,HR:0.114,96%CI:0.034-0.390,P=0.0005),三联组较双联组相对风险降低88.51%,其中
三联组心源性死亡、紧急靶血管血运重建的发生率低于双联组,差异具有统计学意义,但两组间心肌梗死的发生率无统计学差异。(3)两组中均无严重出血事件,三联组轻度出血事件发生8例(0.45%),双联组发生4例(0.35%),差异无统计学意义(P=0.6720)。三联组血小板减少症发生8例(0.45%),双联组发生1例(0.09%),差异也无统计学意义(P=-0.083)。h.老年ACS患者:(1)虽然两组间老年ACS患者的年龄、高脂血症和急性心肌梗死比率、右冠病变的比率、PIC前病与变狭窄程度、左室射血分数有差异,但通过CoX分析发现以上因素对终点事件的发生无影响,两组老年ACS患者其余基线资料的比较无统计学差异。(2)三联组老年ACS患者主要终点事件ST的发生率低于双联组(0.096%vs.1.19%, HR:13.422,95%CI:1.654-109.240, P=0.015),三联组较双联组相对风险降低91.93%。三联组次要终点事件MACE的发生率也低于双联组(0.192%vs.1.528%, HR:8.015,95%CI:1.732-37.094, P=0.0078),三联组较双联组相对风险降低87.43%,其中三联组紧急靶血管血运重建的发生率低于双联组,差异具有统计学意义,但两组间心源性死亡、心肌梗死的发生率无统计学差异。(3)两组间不良反应的比较:两组中均无严重出血事件,三联组轻度出血事件发生3例(0.29%),双联组发生1例(0.17%),差异无统计学意义(P=1.00)。三联组血小板减少症发生3例(0.29%),双联组发生0例(0.00%),差异无统计学意义(P=0.482)。
结论:与双联组相比,三联组ACS患者PCI术后30天内发生ST和MACE的风险明显降低,而出血风险及血小板减少症的发生率并没有增加。同样,与双联组老年ACS患者相比,三联组老年ACS患者PCI术后30天内发生ST和MACE的风险也明显降低,而出血风险及血小板减少症的发生率并没有增加。
Objective:A retrospective study to investigate the safety and efficacy of triple anti-platelet therapy(low-dose tirofiban plus aspirin and clopidogrel)comparing to dual anti-platelet therapy (aspirin and clopidogrel) by analyzing the incidence of stent thrombosis (ST) and major adverse cardiac events (MACE) within30days after implantation of drug-eluting stent (DES) in patients with acute coronary syndrome (ACS).Then selecting the old acute coronary syndrome patients who is more than or equal to60yesrs old and dividing to the triple anti-platelet group and dual anti-platelet therapy group, we investigated the safety and efficacy of triple anti-platelet therapy comparing to dual anti-platelet therapy by analyzing the incidence of ST and MACE within30days after implantation of DES.
Method:we enrolled2904ACS patients who underwent coronary stenting with DES from March2004to November2010.Some patients were treated with dual anti-platelet therapy (DAT, n=1145) while others with triple anti-platelet therapy (TAT, n1759). We compared the incidence of ST,MACE and side effects between the two groups within30days after PCI. Then, selecting1629senile patients(more than or equal to60years old) and dividing to the triple anti-platelet group(n=1040)and dual anti-platelet therapy group(n=589), we investigated the safety and efficacy of triple anti-platelet therapy comparing to dual anti-platelet therapy by analyzing the incidence of ST and MACE within30days after implantation of DES.
Result:a. the ACS patients:(1) Although there are significant differences between the two groups in age,the degree of coronary stenosis, the ratio of smoking, diabetes, hyperlipidemia and coronary diffuse lesion, they have no influence to the end points by cox anlalysis. The rest of the baseline between the two groups is similar.(2)The incidence of primary end point (ST) is lower in TAT group than DAT group (0.11%vs.1.05%, HR:0.108,95%CI:0.024-0.483,P=0.0036), reducing the relative risk by89.52%.In addition,the incidence of secondary end point (MACE) is also lower in TAT group than DAT group(0.17%vs.1.48%, HR:0.114,95%CI:0.034-0.390, P0.0005) which reduced the relative risk by88.51%.Among the total,the incidence of cardiac death and urgent target vessel revascularization in TAT group is lower than DAT group and the difference is significant. However, there is no difference between the two groups in the incidence of myocardial infarction.(3)Both of the two groups have no severe hemorrhage,the incidence of mild hemorrhage is similar in the two groups(0.45%vs.0.35%, p=0.6720).Besides,the incidence of thrombocytopenia between the two groups is also similar.(0.45%vs.0.09%, p=0.083). b. the senile ACS patients:(1) Although there are significant differences between the two groups in age, hyperlipidemia, the ratio of acute myocardial infarction and right coronary artery lesion, left ventricular ejection fraction, they have no influence to the end points by cox anlalysis. The rest of the baseline between the two groups is similar.(2)The incidence of primary end point (ST) is lower in senile TAT group than senile DAT group(0.096%vs.1.19%, HR:13.422,95%CI:1.654-109.240,P=0.015), reducing the relative risk by91.93%.In addition,the incidence of secondary end point (MACE) is also lower in senile TAT group than senile DAT group(0.192%vs.1.528%, HR:8.015,95%CI:1.732-37.094,P=0.0078) which reduced the relative risk by87.43%.Among the total,the incidence of urgent target vessel revascularization in senile TAT group is lower than senile DAT group and the difference is significant. However, there is no difference between the two groups in the incidence of myocardial infarction and cardiac death.(3)Both of the two groups have no severe hemorrhage,the incidence of mild hemorrhage is similar in the two groups(0.29%vs.0.17%, p=1.00).Besides,the incidence of thrombocytopenia between the two groups is also similar.(0.29%vs.0.00%, p-0.482).
Conclusion:The patients with ACS in the TAT group have significant lower incidence of ST and MACE than the DAT group within30days after PCI. While the risk of bleeding and the incidence of thrombocytopenia are not increased. Similar, The senile patients with ACS in the TAT group have significant lower incidence of ST and MACE than the senile DAT group within30days after PCI. While the risk of bleeding and the incidence of thrombocytopenia are not increased.
引文
[1]CutlipDE, Baim DS, Ho KK, et al. Stent thrombosis in the modern era:a pooled analysis of multicenter coronary stent clinicaltrials [J]. Circulation,2001,103(15): 1967-1971.
[21 Orford JL, Lennon R, Melby S, et al. Frequency and correlates of coronary stent thrombosis in the modern era:analysis of a single center registry [J]. J Am Coll Cardiol,2002,40(9):1567-1572.
[3]Elcioglu OC, Ozkok A, Akpmar TS, et al. Severe thrombocytopenia and alveolar hemorrhage represent two types of bleeding tendency during tirofiban treatment: case report and literature review [J]. Int J Hematol,2012,96(3):370-375.
[4]Cutlip DE, Windecker S, MehranR,et al. Clinical end points in coronary stent trials:a case for standardized definitions [J].Circulation,2007,115(17):2344-2351.
[5]Rodriguez AE, Mieres J, Fernandez-Pereira C, et al. Coronary stent thrombosis in the current drug-eluting stent era:insights from the ERACI 111 trial [J]. J Am Coll Cardiol,2006,47(1):205-207.
[6]Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors and outcome of thrombosis after successful implantation of drug-eluting stents [J]. JAMA,2005, 293 (17):2126-2130.
1[7] Rakesh KS, Hanumanth KR, Vibhuti NS, et al. Aspirin and clopidogrel hyporesponsiveness and nonresponsiveness in patients with coronary artery stenting [J]. Vase Health Risk Manag,2009,5(11):965-972.
[8]Lau WC, Gurbel PA, Watkins PB, et al. Contribution of hepatic cytochrome P450 3A4 metabolic activity to the phenomenon of clopidogrel resistance [J]. Circulation,2004,109(2):166-171.
[9]Softer D, Moussal, HarjaiKJ, et al. Impact of angina class on inhibition of platelet aggregation following clopidogrel loading in patients undergoing coronary intervention:do we need more aggressive dosing regimens in unstable angina? [J]. Catheter Cardiovasc Interv,2003,59(1):21-25.
[10]Matetzky S, Shenkman B, Guetta V, et al. Clopidogrel resistances associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction [J]. Circulation,2004,109(25):3171-3175.
[11]Cattaneo M. Aspirin and clopidogrel:efficacy, safety and the issue of drug resistance [J]. Arterioscler Thromb Vase Biol,2004,24(11):1980-1987.
[12]Patrono C, Coller B, Dalen JE, et al. Platelet-active drugs:the relationships among dose, effectiveness and side effects [J]. Chest,1998,114(5 Suppl): 470S-488S.
[13]Angiolillo DJ, Bernardo E, Sabate M, et al. Impact of platelet reactivity on cardiovascular outcomes in patients with type 2 diabetes mellitus and coronary artery disease [J]. J Am Coll Cardiol,2007,50(16):1541-1547.
[14]Gurbel PA, Bliden KP, Samara W, et al. Clopidogrel effect on platelet reactivity in patients with stent thrombosis:results of the CREST Study [J]. J Am Coll Cardiol,2005,46(10):1827-1832.
[15]Gurbel PA, Bliden KP, Guyer K, et al. Platelet reactivity in patients and recurrent events post stenting:results of the PREPARE POST-STENTING Study [J]. J Am Coll Cardiol,2005,46(10):1820-1826.
[16]lleitzer T, Ollmann I, Koke K, et al. Platelet glycoprotein IIb/IIIa receptor blockade improves vaseular nitrieoxide bioavailability in patients with coronary artery disease [J]. Cireulation,2003,108(5):530-541.
[17]Hlmouehi DA, Bates ER. Platelet glycoprotein Ⅱ b/Ⅲa inhibitor therapy in non ST segment Elevation acute coronary syndromes [J]. Minerva Cardioangiol, 2003,51(5):547-560.
[18]Wamlloltz A, Ostad MA, Heitzer T, et al. Effect of tirofiban on Percutaneous coronary intervention-induced endothelial dysfunction in Patients with stable coronary artery disease [J]. Am J Cardiol,2005,95(1):20-23.
[19]De Luca G, Smit JJ, Emst N, et al. Impact of adjunctive tirofiban administration on myocardial perfusion and mortality in patients undergoing primary angioplasty for ST-Segment elevation myocardial infarction [J]. Thromb IIaemost,2005,93(5):820-823.
[20]Kuniehika H, Ben Yehuada O, Lafitte S, et al. Effects of glycoprotein Ⅱ b/Ⅲa inhibition on microvascular flow after coronary reperfusion. A quantitative myocardial contrast echocardiography study [J]. J Am Coll Cardiol,2004,43(2): 276-283.
[21]A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators [J]. N Engl J Med,1998,338(5):1498-1505.
122] Inhibition of the platelet glycoprotein Ⅱ b/Ⅲa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators [J]. N Engl J Med,1998,338(5): 1488-1497.
[23]蒙碧波,吕传柱,蒋宜颖.经皮冠状动脉介入治疗急性冠脉综合征的进展.中华急诊医学杂志[J],2005,14(8):696-698.
1241 Manoukian SV, Feit F, MehranR, et al. Impact of major bleeding on 30-day mortality and clinical outcomes in patients with acute coronary syndromes. ananalysis from the ACUITY Trial [J]. J Am Coll Cardiol,2007,49(12): 1362-1368.
[25]Fox KAA, Bassand JP, Mehta SR, et al. On behalf of the OASIS-5 Investigators. Influence of renal function on the efficacy and safety of fondaparinux relative to enoxaparin in non-ST-segment elevation acute coronary syndromes [J]. Ann Intern Mcd,2007,147(5):304-310.
1261 Iluxtable LM, Tafreshi MJ, Rakkar AN. Frequency and management of thrombocytopenia with the glycoprotein Ⅱ b/Ⅲa receptor antagonists [J]. The American journal of cardiology,2006,97(3):426-429.
[27]Kinnaird TD, Stabile E, MintzGS, ct al. Incidence, predictors, and prognostic implications of bleeding and blood transfusion following percutaneous coronary intcrvcntions[J]. The American journal of cardiology,2003,92(8):930-935.
[28]Feit F, Voeltz MD, Attubato MJ, et al. Predictors and impact of major hemorrhage on mortality following percutaneous coronary intervention from the REPLACE-2 trial [J]. The American journal of cardiology,2007,100(9):1364-1369.
[29]Labinaz M, Ho C, Banerjee S, et al. Meta-analysis of clinical efficacy and bleeding risk with intravenous glycoproteinⅡ b/Ⅲa antagonists for percutaneous coronary intervention [J]. Can J Cardiol,2007,23(12):963-970.
[30]Aster RH, Curtis BR, Bougie DW, et al. Thrombocytopenia associated with the use of GP Ⅱ b/Ⅲa inhibitors:Position paper of the ISTH working group on thrombocytopenia and GP Ⅱ b/Ⅲa inhibitors [J]. J Thromb Haemost, 2006,4(3):678-679.
[31]Aster RⅡ. Immune thrombocytopenia caused by glycoprotein Ⅱ b/Ⅲa inhibitors [J]. Chest,2005,127(2 suppl):538-539.
[32]Effects of platelet glycoprotein Ⅱ b/Ⅲa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. The RESTORE Investigators.Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis [J]. Circulation, 1997,96(5):1445-1453.
[33]Merlini PA, Rossi M, Menozzi A, et al. Thrombocytopenia caused by abciximab or tirofiban and its association with clinical outcome in patients undergoing coronary stenting[J]. Circulation,2004,109:2203-2206.
[34]沈冲,方雪花,赵炳朕,等.半剂量替罗非班联合PCI对早期肾功能不全急性心肌梗死患者的疗效及安全性[J].心血管康复医学杂志,2012,21(3)297-300.
[35]张宾,高传玉.低剂量替罗非班在中高危急性冠脉综合征患者安全性及有效性研究[D].保存地:郑州大学,年份:2011.
[36]Goodman SG, Huang W, Yan AT. The expanded Global Registry of Acute Coronary Events:baseline characteristics, management practices, and hospital outcomes of patientswithacute coronary syndromes [J]. Am Heart J,2009,158(2): 193-201.
[37]梁岩,朱俊,谭慧琼,等.中国地区非ST抬高急性冠脉综合征患者生存时间的影响因索分析[J].中华医学杂志,2005,85(13):873.
[38]杨艳敏,朱俊,谭慧琼,等.中国ST段抬高的急性心肌梗死临床特征及治疗现状[J].中华医学杂志,2005,85(31):2176.
[39]刘水铭,彭晓,严祥,等.男性吸烟者细胞钻附分子和相关细胞因子水平的观察[J].中国循环杂志,2010,17(1):50-55.
[40]刘晓宁,张春玲,武文君,等.年轻人冠合病危险因素分布及聚集状况[J].中华心血管病杂志,2008,31(2):87-89.
[41]胡大一.急性冠状动脉综合征的治疗新对策和新模式[J].中国介入心脏病学杂志,2011,10(1):3.
[42]张静,赵吉光,祝金明,等.应用血管内镜探讨老年急性冠脉综合征患者的发病机制[J].中国老年学杂志,2006,26(11):1489-1490.
[43[ Romano M, Buffoli F, Lettieri C, et al. No reflow in patients undergoing primary angioplasty for acute myocardial infarction at high risk:incidence and predictive factors [J]. Minerva Cardioangiol,2005,53(1):7-14.
[44]Fox KA, Pool-willson PA, Clayton PC, et al.5-year outcome of interventional strategy in non-ST elevation acute coronary syndrome:the British Heart Foundation RITA3 randomised trial [J]. Lancet,2005,366(9489):914-920.
[45]蔡燕军,胡晓晟,傅文中.非ST段抬高急性冠脉综合征患者的临床特点分析.心脑血管病防治[J],2008,8(4):276-277.
[46]Huffinyer J, Raphael J. Physiology and pharmacology of myocardial preconditioning and postconditioning. Semin Cardiothorac Vase Anesth,2009, 13(1):5-18.
[1]Serruys PW, de Jaegere P, Kiemeneij F, et al. A comparison of balloon expandable stent implantation with balloon angioplasty in patients with coronary artery disease [J]. N Engl J Med,1994,331(8):489-495.
[2]Kuchulakanti PK, Chu WW, Torguson R, et al. Correlates and long-term outcomes of angiographically proven stent thrombosis with sirolimus and paclitaxel eluting stenls [J]. Circulation,2006,113(8):1108-1113.
[3]Rodriguez AE, Mieres J, Fernandez-Pereira C, et al. Coronary stent thrombosis in the current drug-eluting stent era:insights from the ERACI III trial [J]. J Am Coll Cardiol,2006,47(1):205-207.
[4]Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors and outcome of thrombosis after successful implantation of drug-eluting stents [J]. JAMA,2005, 293(17):2126-2130.
[5]Hwang CW, Levin AD, Jonas M, et al. Thrombosis modulates arterial drug distribution for drug-eluting stents [J]. Circulation,2005,111(13):1619-1626.
[6]Kotani J, Awata M, Nanto S, et al. Incomplete Neointimal Coverage of Sirolimus-Eluting Stents:Angioscopic Findings [J]. J Am Coll Cardiol,2006, 47(10):2108-2111.
[7]Joner M, Finn AV, Farb A, et al. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk [J]. J Am Coll Cardiol,2006,48(1): 193-202.
[8]Tamura A, Watanabe T, Nagase K, et al. Circadian Variation in Symptomatic Subacute Stent Thrombosis After Bare Metal Coronary Stent Implantation [J].Am J Cardiol,2006,97(2):195-197.
[9]Urban P, Gershlick AH, Guagliumi G, et al. Safety of coronary sirolimus-eluting stents in daily clinical practice:one-year follow-up of the e-Cypher registry [J]. Circulation,2006,113(11):1434-1441.
[10]Fujii K, Carlier SG, Mintz GS, et al. Stent under expansion and residual reference segment stenosis are related to stent thrombosis after sirolimus-eluting stent implantation:an intravascular ultrasound study [J]. J Am Coll Cardiol, 2005,45(7):995-998.
[11]Schiele F, Meneveau N, Vuillemenot A, et al. Impact of intravascular ultrasound guidance in stent deployment on 6-month restenosis rate:a multicenter, randomized study comparing two strategies-with and without intravascular ultrasound guidance. RESIST Study Group. Restenosis after IVUS guided Stenting [J]. J Am Coll Cardiol,1998,32(2):320-328.
[12]Finn AV, Joner M, Nakazawa G, et al. Pathological correlates of late drug-eluting stent thrombosis:strut coverage as a marker of endothelialization [J]. Circulation, 2007,115(18):2435-2441.
[13]Steffel J, Latini RA, Akhmedov A, et al. Rapamycin, but not FK-506, increases endothelial tissue factor expression:implications for drug-eluting stent design [J]. Circulation,2005,112(13):2002-2011.
[14]Stahli BE, Camici GG, Steffel J, et al. Paclitaxel enhances thrombin-induced endothelial tissue factor expression via c-Jun terminal NH2 kinase activation [J]. Circ Res,2006,99(2):149-155.
[15]Nebeker JR, Virmani R, Bennett CL, et al. Hypersensitivity cases associated with drug-eluting coronary stents:a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project [J]. J Am Coll Cardiol,2006, 47(1):175-181.
[16]Moussa I, Di Mario C, Reimers B, et al. Subacute stent thrombosis in the era of intravascular ultrasound-guided coronary stenting without anticoagulation: frequency, predictors and clinical outcome [J]. J Am Coll Cardiol, 1997,29(1):6-12.
[17]Schuhlen H, Kastrati A, Dirschinger J, et al. Intracoronary stenting and risk for major adverse cardiac events during the first month [J]. Circulation,1998,98(2): 104-111.
[18]Park DW, Park SW, Park KH, et al. Frequency of and risk factors for stent thrombosis after drug-eluting stent implantation during long-term follow-up [J]. Am J Cardil,2006,98(3):352-356.
[19]Silva JA, Ramee SR, White CJ, et al. Primary stenting in acute myocardial infarction:influence of diabetes mellitus in angiographic results and clinical outcome [J]. Am Heart J,1999,138(3 Pt1):446-455.
[20]张俊杰,陈淮沁,李志恒,等.比较CypherTM和TaxusTM支架在冠心病合并糖尿病患者中应用的安全性和有效性[J].介入放射学杂志,2005,14(6):569-572.
[21]Ong AT, Hoye A, Aoki J, et al. Thirty-day incidence and six-month clinical outcome of thrombotic stent occlusion after bare-metal, sirolimus or paclitaxel stent implantation [J]. J Am Coll Cardiol,2005,45(6):947-953.
[22]Ge L, Airoldi F, Iakovou I, et al. Clinical and angiographic outcome after implantation of drug-eluting stents in bifurcation lesions with the crush stent technique:importance of final kissing balloon post-dilation [J]. J Am Coll Cardiol,2005,46(4):613-620.
123] Finn AV, Kolodgie FD, Harnek J, et al. Differential response of delayed healing and persistent inflammation at sites of overlapping sirolimus-or paclitaxel-eluting stents [J]. Circulation,2005,112(2):270-278.
[24]Marret E, Collet JP, Albaladejo P, et al. Thrombosis after implantation of drug-eluting stents [J]. JAMA,2006,295(1):36.
[25]Ong AT, Me Fadden EP, Regar E, et al. Late angiographic stent thrombosis (LAST) events with drug-eluting stents [J]. J Am Coll Cardiol,2005,45(12): 2088-2092.
[26]Angiolillo DJ, Fernandez-OrtizA, Bernardo E, et al. Variability in individual responsiveness to clopidogrel clinical implications, management and future perspectives [J]. J Am Coll Cardiol,2007,49(14):1505-1516.
[27]Cattaneo M. Aspirin and clopidogrel:efficacy, safety and the issue of drug resistance [J]. Arterioscler Thromb Vase Biol,2004,24(11):1980-1987.
[28]Patrono C, Coller B, Dalen JE, et al. Platelet-active drugs:the relationships among dose, effectiveness and side effects [J]. Chest,1998,114(5Suppl):470S-488S.
[29]Angiolillo DJ, Bernardo E, Sabate M, et al. Impact of platelet reactivity on cardiovascular outcomes in patients with type 2 diabetes mellitus and coronary artery disease [J]. J Am Coll Cardiol,2007,50(16):1541-1547.
[30]Gurbel PA, Bliden KP, Samara W, et al. Clopidogrel effect on platelet reactivity in patients with stent thrombosis:results of the CREST Study [J]. J Am Coll Cardiol,2005,46(10):1827-1832.
[31]Gurbel PA, Bliden KP, Guyer K, et al. Platelet reactivity in patients and recurrent events post stenting:results of the PREPARE POST-STENTING Study[J]. J Am Coll Cardiol,2005,46(10):1820-1826.
[32]Lau WC, Gurbel PA. Antiplatelet drug resistance and drug-drug interactions:role of cytochrome P450 3A4 [J]. Pharm Res,2006,23(12):2691-2708.
[33]Born GV. Aggregation of blood platelets by adenosine diphosphate and its reversal [J].Nature,1962,194(37):927-929.
[34]Greer DM. Aspirin and antiplatelet agent resistance:implications for prevention of secondary stroke [J]. CNS Drugs,2010,24(12):1027-1040.
[35]Patti G, Colonna G, Pasceri V, et al. Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention:results from the ARMYDA-2 (Antiplatelet therapy for Reduction of Myocardial Damage during Angioplasty) study [J]. Circulation,2005,111(16):2099-2106.
[36]Catella-Lawson, Reilly MP, Kapoor SC, et al. Cyclo-oxygenase inhibitors and the antiplatelet effects of aspirin [J]. N Engl J Med,2001,345(25):1809-1817.
137] Fitzgerald DJ, Maree A. Aspirin and clopidogrel resistance [M]. Hematology Am Soc Hematol Educ Program,2007:114-120.
[38]Lau WC, Waskell LA, Watkins PB, et al. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation:a new drug drug interaction [J]. Circulation,2003,107(1):32-37.
[39]杜彦梅CHARISMA研究:氯吡格雷与他汀类药物之间不存在相互影响[J].中国心血管病研究杂志,2008,6(1):21.
[40]Papp E, Ilavasi V, Bene J, et al. Glycoprotein Agene (P1A) polymorphism and aspirin resistance:is there any correlation [J]. Ann Pharmacother, 2005,39(6):1013-1018.
[41]Mikkelsson J, Perola M, Laippala P, et al. Glycoprotein Ⅲa PI (A1/A2) polymorphism and sudden cardiac death [J]. J Am Coll Cardiol,2000,36(4): 1317-1323.
[42]Gachet C. Regulation of platelet functions by P2 receptors [J]. Annu Rev Pharmacol Toxicol,2006,46:277-300.
[43]Fontana P, Reny JL. Frequently asked questions on clopidogrel treatment: indications, resistance and biological evaluation in vascular patients [J]. Rev Med Suisse,2008,4(143):360-363.
[44]Cuisset T, FrereC, Quilici J, et al. Role of the T744C polymorphism of the P2Y12 gene on platelet response to a600-mg loading dose of clopidogrel in 597 patients with non-ST-segment elevation acute coronary syndrome [J]. Thromb Rcs,2007,120(6):893-899.
[45]Lau WC, Gurbel PA, Watkins PB, et al. Contribution of hepatic cytochrome P4503A4 metabolic activity to the phenomenon of clopidogrel resistance [J]. Circulation,2004,109(2):166-171.
1461 Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel [J]. N Engl J Med,2009,360(4):354-362.
[47]Yee DL, Sun CW, Bergeron AL, et al. Aggregometry detects platelet hyperreactivity in healthy individuals [J]. Blood,2005,106(8):2723-2729.
[48]Gum PA, Kottke-Marchant K, Poggio ED, et al. Profile and prevalence of aspirin resistance inpatients with cardiovascular disease [J]. Am J Cardiol,2001,88(3): 230-235.
[49]Pemerstorfer T, Stohlawetz P, Stummvoll G, et al. Low-dose aspirin does not lower in vivo platelet activation in healthy smokers [J]. Br J Haematol, 1998,102(5):1229-1231.
[50]Friend M, Vucenik I, Miller M. Research pointers:platelet responsiveness to aspirin in patients with hyperlipidaemia [J]. BMJ,2003,326(7380):82-83.
[51]Tamminen M, Lassila R, Westerbacka J, et al. Obesity is associated with impaired platelet-inhibitory effect of acetylsalicylic acid in non-diabetic subjects [J]. Int J Obes Relat Metab Disord,2003,27(8):907-911.
[52]Cox D, Maree AO, Dooley M, et al. Effect of enteric coating on antiplatelet activity of low-dose aspirin in healthy volunteers [J]. Stroke,2006,37(8):2153-2158.
1531 Caplain H, Donat F, GaudC, et al. Pharmacokinetics of clopidogrel [J]. Semin Thromb Hemost,1999,25(Suppl 2):25-28.
[54]Cotter G, Shemesh E, Zehavi M, et al. Lack of aspirin effect:aspirin resistance or resistance to taking aspirin? [J]. Am Heart J,2004,147(2):293-300.
[55]Okabe T, Mintz GS, Buch AN, et al. Intravascular ultrasound parameters associated with stent thrombosis after drug-eluting stent deployment [J]. Am J Cardiol,2007,100(4):615-620.
[56]Choi SY, Witzenbichler B, Maehara A, et al. Intravascular ultrasound findings of early stent thrombosis after primary percutaneous intervention in acute myocardial infarctioira harmonizing outcomes with revascularization and stents in acute myocardial infarction (HORIZONS-AMI) substudy [J]. Circ Cardiovasc Interv,2011,4(3):239-247.
[57]Fitzgerald PJ, Oshima A, Hayase M, et al.Final results of the Can Routine Ultrasound Influence Stent Expansion (CRUISE) study [J]. Circulation, 2000,102(5):523-530.
[58]Roy P, Sterinberg DH, Sushinsky SJ, et al. The potential clinical utility of intravascular ultrasound guidance in patients undergoing percutaneous coronary intervention with drug-eluting stents [J]. Eur Heart J,2008,29(15):1851-1857.
[59]Mintz GS, Weissman NJ. Intravascular ultrasound in the drug-eluting stent era [J]. J Am Coll Cardio,2006,48(3):421-429.
[60]Park SJ, Kim YH, Lee BK, et al. Sirolimus-eluting stent implantation for unprotected left main coronary artery stenosis:comparison with bare metal stent implantation [J]. J Am Coll Cardiol,2005,45(3):351-356.
[61]Seung KB, Kim YH, Park DW, et al. Effectiveness of sirolimus-eluting stent implantation for the treatment of ostial left anterior descending artery stenosis with intravascular ultrasound guidance [J]. J Am Coll Cardiol,2005,46(5): 787-792.
[62]Shimada Y, Honda Y, Kongo Y, et al. Sirolimus-eluting stent implantation in small coronary arteries:predictors of long-term stent patency and neointimal hyperplasia [J]. Circulation,2005,69(6):112-117.
[63]Takano Y, Higgins JR, Tobis JM, et al.New stent delivery systems do not provide optimal stent expansion [J]. J Am Coll Cardiol,2001,37(suppl A):48A.
[64]Brodie BR, Cooper C, Jones M, et al. Is adjunctive balloon post dilatation necessary after coronary stent deployment? Final results from the POSTTT trial [J]. Catheter Cardiovasc Interv,2003,59(2):184-192.
165] Cheneau E, Sailer LF, Escolar E, et al.Underexpansion of sirolimus-eluting stents incidence and relationship to delivery pressure [J]. Catheter Cardiovasc Interv,2005,65(2):222-226.
[66]Colombo A, Hall P, Nakamura S, et al. Intracoronary stenting without anticoagulation accomplished with intravascular ultrasound guidance [J]. Circulation,1995,91(6):1676-1688.
[67]Ormiston JA, Serruys PW. Bioabsorbable coronary stents [J]. Circ Cardiovasc Interv,2009,2(3):255-260.
[68]Maeng M, Jensen LO, Falk E, et al. Negative vascular remodeling after implantation of bioabsorbable magnesium alloy stents in porcine coronary arteries:a randomised comparison with bare-metal and sirolimus eluting stents [J]. Heart,2009,95(3):241-246.
[69]Erbel R, Di Mario C, Bartunek J, et al. Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents:a prospective,non-randomized multicentre trial [J]. The Lancet,2007,369(9576):1869-1875.
[70]Waksman R. Promise and challenges of bioabsorbable stents [J]. Catheterization and Cardiovascular Interventions,2007,70(3):407-414.
[71]卢光,张建,李建新,等.血管组织工程生物材料细胞相容性的评价[J].首都医科大学学报,2006,27(3):321-324.
[721 Strandberg E, Zeltinger J, Schulz DG, et al.Late positive remodeling and late lumen gain contribute to vascular restoration by a non-drug eluting bioresorbable scaffold:a four-year intravascular ultrasound study in nonnal porcine coronary arteries [J]. Circ Cardiovasc Interv,2012,5(1):39-46.
[73]Wang TH, Bhatt DL, Topol EJ. Aspirin and clopidogrel resistance:an emerging clinical entity [J]. Eur Heart J,2006,27(6):647-654.
[74]Angiolillo DJ, Shoemaker SB, Desai B, et al. Randomized comparison of a high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease:results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) study [J]. Circulation,2007,115(6):708-716.
[75]Jemberg T, Payne CK, Winters KJ, et al. Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of nonresponders compared with clopidogrel in asprin treated patients with stable coronary artery disease [J]. Eur Heart J,2006,27(10):1166-1173.
[76]Wiviott SD, Braunwald E, McCabe CH, et al. Intensive oral antiplatelet therapy for reduction of ischaemic events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous coronary intervention and stenting in the TRITON-TIMI 38 trial:a subanalysis of a randomised trial [J]. Lancet,2008,371 (9621):1353-1363.
[77]Greenbaum AB, Ohman EM, Gibson CM, et al. Preliminary experience with intravenous P2Y12 platelet receptor inhibition as an adjunct to reduced-dose alteplase during acute myocardial infarction:results of the Safety, Tolerability and Effect on Patency in Acute Myocardial Infarction (STEP-AMI) angiographic trial [J]. Am Heart J,2007,154(4):702-709.
[78]BellEmain-Appaix A, Brieger D, Beygui F, et al. New P2Y12 inhibitors versus clopidogrel in percutaneous coronary intervention:a meta-analysis [J]. J Am CollCardiol,2010,56(19):1542-1551.
[79]Cattaneo M,Podda GM. State of the art of new P2Y12 antagonists [J]. Intern Emerg Med,2010,5(5):385-391.
[80]Ramaraj R, Movahed MR, Hashemzadeh M. Novel antiplatelet agent ticagrelor in the management of acute coronary syndrome [J]. J Interv Cardiol,2011,24(3): 199-207.
[81]Cayla G, Montalescot G, Collet JP. Ticagrelor to prevent restenosis:new drug for an old hypothesis? [J]. Arterioscler Thromb Vase Biol,2010,30(12):2320-2322.
[82]Pollack CV. Emerging oral antiplatelet therapies for acute coronary syndromes [J]. Hosp Pract,2010,38(4):29-37.
[83]Ting HJ, Khasawneh FT. Platelet function and isoprostane biology:should isoprostanes be the newest member of the orphan ligand family? [J]. J Biomed Sci,2010,17(1):24.
[84]The RAPT Investigators. Randomized trial of ridogrel, a combined thromboxane A2 synthase inhibitor and thromboxane A2/prostaglandin endoperoxide receptor antagonist, versus aspirin as adjunct to thrombolysis in patients with acute myocardial infarction:the Ridogrel versus Aspirin Patency Trial (RAPT) [J]. Circulation,1994,89(2):588-595.
[85]Choi J, Kermode JC. New therapeutic approaches to combat arterial thrombosis: better drugs for old targets, novel targets, and future prospects [J]. Mol Interv,2011,11(2):111-123.
[86]Choi J, Kermode JC. New therapeutic approaches to combat arterial thrombosis: better drugs for old targets, novel targets, and future prospects [J]. Mol Intcrv,2011,11(2):111-123.
[87]Nagatomo T, Rashid M, Muntasir HA, et al. Functions of 5-HT2A receptor and its antagonists in the cardiovascular system [J]. Pharmacol Ther,2004,104(1): 59-81.
[88]Shinohara Y, Nishimaru K. Sarpogrelate versus aspirin in secondary prevention of cerebral infarction:differential efficacy in diabetes? Subgroup analysis from S-ACCliSS [J]. Stroke,2009,40(8):2862-2865.
[89]Lev El, Patel RT, Maresh KJ, et al. Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention:the role of dual drug resistance [J]. J Am Coll Cardiol,200647(l):27-33.
[90]Savi P, Herbert JM. Clopidogrel and ticlopidine:P2Y12 adenosine diphosphate receptor antagonists for the prevention of atherothrombosis [J]. Semin Thromb Hemosl,2005,31(2):174-183.
[91]Buonamici P, Marcucci R, Migliorini A, et al. Impact of platelet reactivity after clopidogrel administration on drug eluting stent thrombosis [J]. J Am Coll Cardiol,2007,49(24):2312-2317.
[92]王建中.加强血小板功能试验在抗血小板药物治疗监测中的应用[J].中华检验医学杂志,2008,31(1):9-11.
[93]Aleil B, Ravanat C, Cazenave JP, et al. Flow cytometric analysis of intraplatelet VASP phosphorylation for the detection of clopidogrel resistance in patients with ischemic cardiovascular diseases [J]. J Thromb Haemost,2005,3(1):85-92.
[94]Golanski J, Pluta J, Baraniak J, et al. Limited usefulness of the PFA-100 for the monitoring of ADP receptor antagonists experience [J]. Clin Chem Lab Med,2004,42(1):25-29.
[95]Michelson AD, Frelinger AL 3rd, Furman MI. Current options in platelet function testing [J]. Am J Cardiol,2006,98(10A):4N-10N.
[96]Gurbel PA, Becker RC, Mann KG, et al. Platelet function monitoring in patients with coronary artery disease [J]. J Am Coll Cardiol,2007,50(19):1822-1834.
[97]Balamuthusamy S, Arora R, Hematologic adverse effects of clopidogrel [J]. Am J Ther,2007,14(1):106-112.
[98]Bougie DW, Wilker PR, Wuitschick ED, et al. Acute thrombocytopenia after treatment with tirofiban or eptifibatide is associated with antibodies specific for ligand-occupied GP Ⅱ b/Ⅲa [J]. Blood,2002,100(6):2071-2076.
[99]杨海鹰.李崇剑,尤士杰,等.替罗非班引起急性血小板减少一例[J].中国循环杂志,2006,21(5):367.
[100]吴桦,付向民.盐酸替罗非班引起严重血小板减低1例[J].中国医药指南,2007,5(10):167.
[101]Ahmed I, Majeed A, Powell R. Heparin induced thrombocytopenia, diagnosis and management update [J]. Postgrad Med J,2007,83(983):575-582.
[102]Manoukian SV, Feit F, Mehran R, et al. Impact of major bleeding on 30-day mortality and clinical outcomes in patients with a cute coronary syndromes. ananalysis from the ACUITY Trial [J]. J Am Coll CardioI,2007,49(12):1362-1368.
1103] Fox KAA, Bassand JP, Mehta SR, et al. On behalf of the OASIS-5 Investigators. Influence of renal function on the efficacy and safety of fondaparinux relative to enoxaparin in non-ST-segment elevation acute coronary syndromes [J]. Ann Intern Med,2007,147(5):304-310.
[104]James N, Riehard H. Drug-indueed thrombocytopenia, Pathogenesis, evaluation and management [J]. Hematology,2009,2009(1):153-158.
1105] Elmouehi DA, Bates ER. Platelet glycoprotein Ⅱ b/Ⅲa inhibitor therapy in non ST segment Elevation acute coronary syndromes [J]. Minerva Cardioangiol, 2003,51(5):547-560.
[106]HeitzerT, Ollmann I, KokeK, et al. Platelet glycoprotein II b/IIIa receptor blockade improves vascular nitrieoxide bioavailability in Patients with coronary artery disease [J]. Cireulation,2003,108(5):530-541.
[107]Warnlloltz A, Ostad MA, Heitzer T, et al. Effect of tirofiban on Percutaneous coronary intervention-induced endothelial dysfunetion in Patients with stable coronary artery disease [J]. Am J Cardiol,2005,95(1):20-23.
[108]De Luca G, Smit JJ, Emst N, et al. Impact of adjunctive tirofiban administration on myocardial Perfusion and mortality in Patients undergoing Primary angioplasty for ST-Segment elevation myocardial infarction [J]. Thromb IIaemost,2005,93(5):820-823.
[109]Kuniehika H, Ben Yehuada O, Lafitte S, et al. Effects of glycoprotein Ⅱ b/Ⅲa inhibition on microvascular flow after coronary reperfusion. A quantitative myocardial contrast echocardiography study [J]. J Am Coll Cardiol,2004,43(2): 276-283.
[110]Iluxtable LM, Tafreshi MJ, Rakkar AN. Frequency and management of thrombocytopenia with the glycoprotein Ⅱ b/Ⅲa receptor antagonists [J]. The American journal of cardiology,2006,97(3):426-429.
[111]Kinnaird TD, Stabile E, Mintz GS, et al. Incidence, predictors, and prognostic implications of bleeding and blood transfusion following percutaneous coronary interventions [J]. The American journal of cardiology,2003,92(8): 930-935.
[112]Manoukian SV, Feit F, Mehran R, et al. Impact of major bleeding on 30-day mortality and clinical outcomes in patients with acute coronary syndromes:an analysis from the ACUITY Trial [J]. J Am Coll Cardiol,2007,49(12): 1362-1368.
[113]Feit F, Voeltz MD, Attubato MJ, et al. Predictors and impact of major hemorrhage on mortality following percutaneous coronary intervention from the REPLACE-2 trial [J]. The American journal of cardiology,2007,100(9): 1364-1369.
[114]Labinaz M, Ho C, Banerjee S, et al. Meta-analysis of clinical efficacy and bleeding risk with intravenous glycoprotein Ⅱ b/Ⅲa antagonists for percutaneous coronary intervention [J]. Can J Cardiol,2007,23(12):963-970.
[115]沈冲,方雪花,赵炳朕,等.半剂量替罗非班联合PCI对早期肾功能不全急性心肌梗死患者的疗效及安全性[J].心血管康复医学杂志,2012,21(3):297-300.
[116]张宾,高传玉.低剂量替罗非班在中高危急性冠脉综合征患者安全性及有效性研究[D].保存地:郑州大学,年份:2011.