“一站式”杂交冠状动脉血运重建术中替格瑞洛与氯吡格雷抗血小板治疗的有效性及安全性比较
|
摘要
目的:比较接受"一站式"杂交冠状动脉血运重建术(HCR)的患者应用替格瑞洛与氯吡格雷的抗血小板疗效及安全性。方法:本研究采取前瞻性开放标签随机研究设计,入选60例拟行"一站式"HCR的患者,术前均长期服用阿司匹林100 mg,每日1次。在术中确认左乳内动脉(LIMA)-左前降支(LAD)旁路通畅后,随机分成两组,氯吡格雷组(n=30)给予氯吡格雷(300 mg负荷,随后75 mg每日1次),替格瑞洛组(n=30)给予替格瑞洛(90 mg首次服用,随后90 mg每日2次)。应用Verify Now P2Y12测量经胃管给予首剂研究药物后0.5 h、1 h、2 h、6 h、24 h的血小板反应单位(PRU)值。记录两组患者术后24 h及72 h胸腔引流量、围术期的血制品使用及出血事件。术后随访3个月,记录随访中发生的主要不良心脑血管事件(MACCE)。结果:在"一站式"HCR中,给予首剂研究药物2 h后,替格瑞洛组即表现了比氯吡格雷组更强的血小板抑制效果(替格瑞洛组PRU:271±51.575 vs氯吡格雷组PRU:313.17±61.161,P=0.008)。给予首剂研究药物6 h后,替格瑞洛组达到适宜的PRU水平(PRU<235)。两组患者的血小板水平在术后早期均出现了下降,两组间差异无统计学意义(P>0.05)。两组患者手术后24 h的胸腔引流量[替格瑞洛组535.0(345.0,902.5)ml vs氯吡格雷组400.0(337.5,567.5)ml,P=0.131]及72 h的胸腔引流量[替格瑞洛组680.0(442.5,1 060.0)ml vs氯吡格雷组575.0(467.5,710.0)ml,P=0.264]差异均无统计学意义。两组患者术后血制品使用量、主要及次要出血事件及随访中的MACCE发生差异均无统计学意义(P>0.05)。结论:替格瑞洛比氯吡格雷具有更强的血小板抑制效果,且替格瑞洛较氯吡格雷组在术后胸腔引流量、主要及次要出血事件,随访中的MACCE事件均无明显差异。在"一站式" HCR中,替格瑞洛较氯吡格雷具有更强的血小板抑制作用且不增加出血风险。
Objectives: This study aimed to evaluate the antiplatelet effects and safety of clopidogrel and ticagrelor in patients during "one-stop" hybrid coronary revascularization(HCR).Methods: This is a single-center, open-label, randomized,prospective study. 60 Patients undergoing one-stop HCR was randomized equally(ratio 1:1) to receive either clopidogrel(300 mg loading dose [LD], 75 mg/day), or to receive ticagrelor(90 mg LD, 90 mg twice daily) after confirmation of LIMA-LAD graft patency. All patients treated with concomitant ASA 100 mg once daily during the treatment period. Platelet reaction units(PRU) were assessed by Verify NowTM P2 Y12 assay at 0.5 h, 1 h, 2 h, 6 h, 24 h after loading dose. Thoracic cavity drainage at 24 h and 72 h after operation was recorded, Perioperative bleeding and the use of blood products as well as the major adverse cardiac or cerebrovascular events(MACCE) rates within3 months post HCR were compared.Results: Ticagrelor produced greater suppression effect on platelet aggregation in patients undergoing HCR. PRU values were 313.17±61.161 in clopidogrel group and 271±51.575 in ticagrelor group at 2 h post LD(P<0.05). Patients in ticagrelor group achieved a proper average PRU value(<235) at 6 h post LD. Amount of thoracic cavity drainage was similar at 24 hours(ticagrelor: 535.0(345.0, 902.5)ml vs clopidogrel: 400.0(337.5, 567.5)ml,P=0.131) and at 72 h(ticagrelor: 680.0(442.5,1060.0)ml vs clopidogrel: 575.0(467.5, 710.0)ml,P=0.264) after HCR. The use of blood products, bleeding events and MACCE were comparable between two groups.Conclusions: Ticagrelor use is associated with greater antiplatelet effect as compared to clopidogrel in patients undergoing HCR procedure. There is no significant difference of thoracic cavity, major and minor bleeding events and MACCE between two groups. Ticagrelor might be a more effective antiplatelet choice as compared to clopidogrel in one-stop HCR.
Objectives: This study aimed to evaluate the antiplatelet effects and safety of clopidogrel and ticagrelor in patients during "one-stop" hybrid coronary revascularization(HCR).Methods: This is a single-center, open-label, randomized,prospective study. 60 Patients undergoing one-stop HCR was randomized equally(ratio 1:1) to receive either clopidogrel(300 mg loading dose [LD], 75 mg/day), or to receive ticagrelor(90 mg LD, 90 mg twice daily) after confirmation of LIMA-LAD graft patency. All patients treated with concomitant ASA 100 mg once daily during the treatment period. Platelet reaction units(PRU) were assessed by Verify NowTM P2 Y12 assay at 0.5 h, 1 h, 2 h, 6 h, 24 h after loading dose. Thoracic cavity drainage at 24 h and 72 h after operation was recorded, Perioperative bleeding and the use of blood products as well as the major adverse cardiac or cerebrovascular events(MACCE) rates within3 months post HCR were compared.Results: Ticagrelor produced greater suppression effect on platelet aggregation in patients undergoing HCR. PRU values were 313.17±61.161 in clopidogrel group and 271±51.575 in ticagrelor group at 2 h post LD(P<0.05). Patients in ticagrelor group achieved a proper average PRU value(<235) at 6 h post LD. Amount of thoracic cavity drainage was similar at 24 hours(ticagrelor: 535.0(345.0, 902.5)ml vs clopidogrel: 400.0(337.5, 567.5)ml,P=0.131) and at 72 h(ticagrelor: 680.0(442.5,1060.0)ml vs clopidogrel: 575.0(467.5, 710.0)ml,P=0.264) after HCR. The use of blood products, bleeding events and MACCE were comparable between two groups.Conclusions: Ticagrelor use is associated with greater antiplatelet effect as compared to clopidogrel in patients undergoing HCR procedure. There is no significant difference of thoracic cavity, major and minor bleeding events and MACCE between two groups. Ticagrelor might be a more effective antiplatelet choice as compared to clopidogrel in one-stop HCR.
引文
[1]Shen L,Hu S,Wang H,et al.One-stop hybrid coronary revascularization versus coronary artery bypass grafting and percutaneous coronary intervention for the treatment of multivessel coronary artery disease:3-year follow-up results from a single institution[J].J Am Coll Cardiol,2013,61(25):2525-2533.DOI:10.1016/j.jacc.2013.04.007.
[2]沈刘忠,胡盛寿,徐波,等.一站式复合技术与冠状动脉旁路移植术及经皮冠状动脉介入治疗在冠状动脉多支病变治疗中的对比研究[J].中国循环杂志,2018,33(1):24-29.DOI:10.3969/j.issn.1000-3614.2018.01.004.
[3]熊辉,沈刘中.杂交技术治疗冠状动脉多支血管病变:现状和展望[J].中国循环杂志,2014,29(2):81-83.DOI:10.3969/j.issn.1000-3614.2014.02.001.
[4]Gao P,Xiong H,Zheng Z,et al.Evaluation of antiplatelet effects of a modified protocol by platelet aggregation in patients undergoing"one-stop"hybrid coronary revascularization[J].Platelets,2010,21(3):183-190.DOI:10.3109/09537101003592700.
[5]Storey RF,Angiolillo DJ,Patil SB,et al.Inhibitory effects of ticagrelor compared with clopidogrel on platelet function in patients with acute coronary syndromes:the PLATO(PLATelet inhibition and patient Outcomes)PLATELET substudy[J].J Am Coll Cardiol,2010,56(18):1456-1462.DOI:10.1016/j.jacc.2010.03.100.
[6]Becker RC,Bassand JP,Budaj A,et al.Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes(PLATO)trial[J].Eur Heart J,2011,32(23):2933-2944.DOI:10.1093/eurheartj/ehr422.
[7]Patrono C,Bachmann F,Baigent C,et al.Expert consensus document on the use of antiplatelet agents.The task force on the use of antiplatelet agents in patients with atherosclerotic cardiovascular disease of the European society of cardiology[J].Eur Heart J,2004,25(2):166-181.DOI:10.1016/j.ehj.2003.10.013.
[8]Gurbel PA,Bliden KP,Hiatt BL,et al.Clopidogrel for coronary stenting:response variability,drug resistance,and the effect of pretreatment platelet reactivity[J].Circulation,2003,107(23):2908-2913.DOI:10.1161/01.CIR.0000072771.11429.83.
[9]Storey RF,Husted S,Harrington RA,et al.Inhibition of platelet aggregation by AZD6140,a reversible oral P2Y12 receptor antagonist,compared with clopidogrel in patients with acute coronary syndromes[J].J Am Coll Cardiol,2007,50(19):1852-1856.DOI:10.1016/j.jacc.2007.07.058.
[10]Bednar F,Osmancik P,Vanek T,et al.Platelet activity and aspirin efficacy after off-pump compared with on-pump coronary artery bypass surgery:results from the prospective randomized trial PRAGUE 11-Coronary Artery Bypass and REactivity of Thrombocytes(CABARET)[J].J Thorac Cardiovasc Surg,2008,136(4):1054-1060.DOI:10.1016/j.jtcvs.2008.03.052.
[2]沈刘忠,胡盛寿,徐波,等.一站式复合技术与冠状动脉旁路移植术及经皮冠状动脉介入治疗在冠状动脉多支病变治疗中的对比研究[J].中国循环杂志,2018,33(1):24-29.DOI:10.3969/j.issn.1000-3614.2018.01.004.
[3]熊辉,沈刘中.杂交技术治疗冠状动脉多支血管病变:现状和展望[J].中国循环杂志,2014,29(2):81-83.DOI:10.3969/j.issn.1000-3614.2014.02.001.
[4]Gao P,Xiong H,Zheng Z,et al.Evaluation of antiplatelet effects of a modified protocol by platelet aggregation in patients undergoing"one-stop"hybrid coronary revascularization[J].Platelets,2010,21(3):183-190.DOI:10.3109/09537101003592700.
[5]Storey RF,Angiolillo DJ,Patil SB,et al.Inhibitory effects of ticagrelor compared with clopidogrel on platelet function in patients with acute coronary syndromes:the PLATO(PLATelet inhibition and patient Outcomes)PLATELET substudy[J].J Am Coll Cardiol,2010,56(18):1456-1462.DOI:10.1016/j.jacc.2010.03.100.
[6]Becker RC,Bassand JP,Budaj A,et al.Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes(PLATO)trial[J].Eur Heart J,2011,32(23):2933-2944.DOI:10.1093/eurheartj/ehr422.
[7]Patrono C,Bachmann F,Baigent C,et al.Expert consensus document on the use of antiplatelet agents.The task force on the use of antiplatelet agents in patients with atherosclerotic cardiovascular disease of the European society of cardiology[J].Eur Heart J,2004,25(2):166-181.DOI:10.1016/j.ehj.2003.10.013.
[8]Gurbel PA,Bliden KP,Hiatt BL,et al.Clopidogrel for coronary stenting:response variability,drug resistance,and the effect of pretreatment platelet reactivity[J].Circulation,2003,107(23):2908-2913.DOI:10.1161/01.CIR.0000072771.11429.83.
[9]Storey RF,Husted S,Harrington RA,et al.Inhibition of platelet aggregation by AZD6140,a reversible oral P2Y12 receptor antagonist,compared with clopidogrel in patients with acute coronary syndromes[J].J Am Coll Cardiol,2007,50(19):1852-1856.DOI:10.1016/j.jacc.2007.07.058.
[10]Bednar F,Osmancik P,Vanek T,et al.Platelet activity and aspirin efficacy after off-pump compared with on-pump coronary artery bypass surgery:results from the prospective randomized trial PRAGUE 11-Coronary Artery Bypass and REactivity of Thrombocytes(CABARET)[J].J Thorac Cardiovasc Surg,2008,136(4):1054-1060.DOI:10.1016/j.jtcvs.2008.03.052.