替格瑞洛与氯吡格雷在非氯吡格雷抵抗PCI患者术后的应用效果
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摘要
目的对比非氯吡格雷抵抗ST段抬高型心肌梗死(STEMI)患者经皮冠状动脉介入(PCI)术后长期服用替格瑞洛与氯吡格雷的疗效与安全性。方法 121例PCI患者随机分为替格瑞洛组(60例)与氯吡格雷组(61例),在口服阿司匹林基础上,替格瑞洛组术后加服替格瑞洛抗血小板治疗,每日2次,每次90 mg;氯吡格雷组加服氯吡格雷治疗,75 mg/d,随访两组术后半年血小板抑制情况、血液流变学指标及血栓标志物变化情况,比较术后1年内出血及主要不良心血管事件(MACE)发生率。结果替格瑞洛组术后半年二磷酸腺苷(ADP)诱导的血小板抑制率〔(17. 3±4. 4) vs(13. 5±3. 8)%〕及全血高切黏度〔(0. 85±0. 18) vs(0. 67±0. 20) m Pa·s〕、低切黏度〔(1. 06±0. 21) vs(0. 89±0. 24) m Pa·s〕、血浆黏度〔(0. 43±0. 10)vs(0. 35±0. 08) m Pa·s〕下降绝对数值均显著高于氯吡格雷组(P均<0. 05);替格瑞洛组术后半年金属基质蛋白酶-9〔(102. 5±26. 7) vs(91. 8±22. 3) mg/L〕、D-二聚体〔(106. 3±21. 5) vs(94. 1±20. 5)μg/L〕、瘦素〔(3. 27±0. 95) vs(2. 89±0. 87)μg/L〕下降绝对数值显著高于氯吡格雷组(P均<0. 05);替格瑞洛组与氯吡格雷组术后1年内出血发生率(14. 0%vs 10. 2%)差异无统计学意义(P>0. 05),替格瑞洛组呼吸困难发生率显著高于氯吡格雷组(15. 8%vs 3. 4%,P<0. 05),而氯吡格雷组术后MACE发生率显著高于替格瑞洛组(16. 9%vs 5. 3%,P<0. 05)。结论对非氯吡格雷抵抗者,替格瑞洛、氯吡格雷分别联合阿司匹林均是PCI术后抗血小板治疗的有效方案,前者能在不明显增加出血事件前提下,降低血小板反应性与血液黏度,并表现出减少MACE的趋势。
Objective To compare the postoperative efficacy and safety of long term using ticagrelor versus clopidogrel on non clopidogrel resistant patients with acute ST-segment elevation myocardial infarction(STEMI)undergoing primary percutaneous coronary intervention(PCI).Methods 121 admitted PCI patients were randomly divided into ticagrelor group(60 cases)and clopidogrel group(61 cases),base on rountine aspirin antiplatelet therapy,ticagrelor group was added with ticagrelor therapy,2 times a day,90 mg each time;clopidogrel group was added with clopidogrel therapy,75 mg/d.The variations hemorheology indexes and thrombosis markers of the two groups were examined,and incidences of hemorrhage and major adverse cardiac events(MACE)within 1 year after PCI were noted and compared.Results The absolute decline values on PIR of ticagrelor group[(17.3±4.4 vs 13.5±3.8)%],high blood viscosity[(0.85±0.18)vs(0.67±0.20)mpa·s],low blood viscosity[(1.06±0.21)vs(0.89±0.24)mpa·s]and plasma viscosity[(0.43±0.10)vs(0.35±0.08)mpa·s]were all significantly higher than those of clopidogrel group(P<0.05).The absolute decline values on MMP-9 of ticagrelor group[(102.5±26.7)vs(91.8±22.3)mg/L],D-dimer[(106.3±21.5)vs(94.1±20.5)μg/L],LEP[(3.27±0.95)vs(2.89±0.87)μg/L]were all significantly higher than those of clopidogrel group either(P<0.05).The postoperative bleeding events of the two groups within 1 year after PCI were similar with each other(14.0%vs 10.2%,P>0.05),breathing difficulties in ticagrelor group was significantly higher than that of clopidogrel group(15.8%vs 3.4%)(P<0.05),and postoperative incidence of MACE in clopidogrel group was significantly higher than that of ticagrelor group(16.9%vs 5.3%,P<0.05).Conclusions For the non clopidogrel resistant STEMI patients,ticagrelor and clopidogrel combined with aspirin are both effective scheme of PCI postoperative antiplatelet therapy,the former therapy could significantly reduce platelet reactivity and viscosity,and with the trend of reducing MACE.
Objective To compare the postoperative efficacy and safety of long term using ticagrelor versus clopidogrel on non clopidogrel resistant patients with acute ST-segment elevation myocardial infarction(STEMI)undergoing primary percutaneous coronary intervention(PCI).Methods 121 admitted PCI patients were randomly divided into ticagrelor group(60 cases)and clopidogrel group(61 cases),base on rountine aspirin antiplatelet therapy,ticagrelor group was added with ticagrelor therapy,2 times a day,90 mg each time;clopidogrel group was added with clopidogrel therapy,75 mg/d.The variations hemorheology indexes and thrombosis markers of the two groups were examined,and incidences of hemorrhage and major adverse cardiac events(MACE)within 1 year after PCI were noted and compared.Results The absolute decline values on PIR of ticagrelor group[(17.3±4.4 vs 13.5±3.8)%],high blood viscosity[(0.85±0.18)vs(0.67±0.20)mpa·s],low blood viscosity[(1.06±0.21)vs(0.89±0.24)mpa·s]and plasma viscosity[(0.43±0.10)vs(0.35±0.08)mpa·s]were all significantly higher than those of clopidogrel group(P<0.05).The absolute decline values on MMP-9 of ticagrelor group[(102.5±26.7)vs(91.8±22.3)mg/L],D-dimer[(106.3±21.5)vs(94.1±20.5)μg/L],LEP[(3.27±0.95)vs(2.89±0.87)μg/L]were all significantly higher than those of clopidogrel group either(P<0.05).The postoperative bleeding events of the two groups within 1 year after PCI were similar with each other(14.0%vs 10.2%,P>0.05),breathing difficulties in ticagrelor group was significantly higher than that of clopidogrel group(15.8%vs 3.4%)(P<0.05),and postoperative incidence of MACE in clopidogrel group was significantly higher than that of ticagrelor group(16.9%vs 5.3%,P<0.05).Conclusions For the non clopidogrel resistant STEMI patients,ticagrelor and clopidogrel combined with aspirin are both effective scheme of PCI postoperative antiplatelet therapy,the former therapy could significantly reduce platelet reactivity and viscosity,and with the trend of reducing MACE.
引文
1 中华医学会心血管病学分会,中华心血管病杂志编辑委员会.急性ST段抬高型心肌梗死诊断和治疗指南[J].中华心血管病杂志,2015;43(5):380-93.
2 吴丹,杨胜利,路靖,等.冠心病患者支架术后根据检测药物代谢酶CYP2C19基因调整抗血小板治疗的价值[J].中国循环杂志,2015;30(3):216-8.
3 Musallam A,Orvin K,Perl L,et al.Effect of modifying antiplatelet treatment to ticagrelor in high-risk coronary patients with low response to clopidogrel(MATTIS)[J].Can J Cardiol,2016;32(10):1246.
4 Angiolillo DJ,Franchi F,Waksman R,et al.Effects of ticagrelor versus clopidogrel in troponin negative patients with low-risk ACS undergoing Ad Hoc PCI[J].J Am Coll Cardiol,2016;67(6):603-13.
5 Gurbel PA,Bliden KP,Butler K,et al.Response to ticagrelor in clopidogrel nonresponders and responders and effect of Switching therapies:the RESPOND study[J].Circulation,2010;121(10):1188-99.
6 Mehran R,Rao SV,Bhatt DL,et al.Standardized bleeding definitions for cardiovascular clinical trials:a consensus report from the Bleeding Academic Research Consortium[J].Circulation,2011;123(23):2736-47.
7 Abdel-Wahab M,Baev R,Dieker P,et al.Long-term clinical outcome of rotational atherectomy followed by drug-eluting stent implantation in complex calcified coronary lesions[J].Catheter Cardiovasc Interv,2013;81(2):285-91.
8 Wisman PP,Roest M,Asselbergs FW,et al.Platelet-reactivity tests identify patients at risk of secondary cardiovascular events:asystematic review and meta-analysis[J].J Thromb Haemost,2014;12(5):736-47.
9 Wen C,Xu H.The new strategy for modulating dyslipidemia:Consideration From updated understanding on high-density lipoprotein[J].Chin J Integr Med,2011;17(6):467-70.
10 唐云.氯吡格雷对PCI患者血小板功能状态及血流变的影响[J].北方药学,2017;14(1):103-4.
11 Abtahian F,Yonetsu T,Vergallo R,et al.Ticagrelor immediately prior to stenting is associated with smaller residual thrombus in patients with acute coronary syndrome[J].Int J Cardiol,2013;168(3):3099-101.
12 梁茜,张健瑜,杨希立,等.急性冠脉综合征合并糖尿病患者经皮冠脉介入术后替格瑞洛与氯吡格雷的疗效比较[J].中国医科大学学报,2016;45(2):145-7.
13 Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology(ESC),Steg PG,James SK,et al.ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation[J].Eur Heart J,2012;33(20):2569-619.
14 Van Haren RM,Valle EJ,Thorson CM,et al.Hypercoagulability and other risk factors in trauma intensive care unit patients with venousthromboembolism[J].J Trauma Acute Care Surg,2014;76(2):443-9.
15 于洪伟,刘奇峰,王玉亭,等.骨桥蛋白和基质金属蛋白酶-9对经皮冠状动脉介入治疗后支架内再狭窄的诊断价值[J].中国循环杂志,2015;30(7):635-7.
16 Skorko A,Thomas M,Mumford A,et al.Research protocol for platelets in out-of-hospital cardiac arrest:an observational,case-controlled,feasibility study to assess coagulation and platelet function abnormalities with ROTEM following out-of-hospital cardiac arrest(PoHCAR)[J].BMJ Open,2017;7(7):e015663.
17 Nguyen PA,Heggermont WA,Vanhaverbeke M,et al.Leptin-adiponectin ratio in pre-diabetic patients undergoing percutaneous coronary intervention[J].Acta Cardiol,2015;70(6):640-6.
18 Bliden KP,Tantry US,Storey RF,et al.The effect of ticagrelor versus clopidogrel on high on-treatment platelet reactivity:combined analysis of the ONSET/OFFSET and RESPOND studies[J].Am Heart J,2011;162(1):160-5.
19 冯春艳,苏东辉,于军.替格瑞洛对冠心病患者经皮冠状动脉介入治疗术后冠脉微循环功能的影响[J].血栓与止血,2016;22(5):507-10.
20 刘晓刚,胡立群,刘玉峰,等.替格瑞洛与氯吡格雷对急性非ST段抬高型心肌梗死患者经皮冠状动脉介入术后炎症因子的影响[J].中国临床药理学杂志,2016;32(9):789-91.
21 张明亮,沈玉华,张立敏,等.替格瑞洛对急性ST段抬高型心肌梗死急诊经皮冠状动脉介入患者血小板聚集率及QT离散度的影响[J].中国老年学杂志,2016;36(15):3667-9.
22 Hansson EC,Jidéus L,berg B,et al.Coronary artery bypass grafting-related bleeding complications in patients treated with ticagrelor or clopidogrel:a nationwide study[J].Eur Heart J,2016;37(2):189-97.
23 Hansson EC,Rexius H,Dellborg M,et al.Coronary artery bypass grafting-related bleeding complications in real-life acute coronary syndrome patients treated with clopidogrel or ticagrelor[J].Eur JCardiothorac Surg,2014;46(4):699-705.
24 Kohli P,Wallentin L,Reyes E,et al.Reduction in first and recurrent cardiovascular events with ticagrelor compared with clopidogrel in the PLATO Study[J].Circulation,2013;127(6):673-80.
25 Di Nicolantonio JJ,Tomek A.In activations,deletions,non-adjudications,and downgrades of clinical endpoints on ticagrelor:serious concerns over the reliability of the PLATO trial[J].Int J Cardiol,2013;168(4):4076-80.
26 Velders MA,Abtan J,Angiolillo DJ,et al.Safety and efficacy of ticagrelor and clopidogrel in primary percutaneous coronary intervention[J].Heart,2016;102(8):617-25.
27 刘然,师树田,索曼,等.对氯吡格雷低反应患者换用替格瑞洛后的有效性与安全性评价[J].中国介入心脏病学杂志,2014;22(1):12-5.
28 Ohman J,Kudira R,Albinsson S,et al.Ticagrelor induces adenosine triphosphate release from human red blood cells[J].Biochem Biophys Res Commun,2012;418(4):754-8.
29 白艳艳,史骏,刘成,等.不同抗血小板药物在ACS患者PCI术后氯吡格雷低反应性中的疗效及安全性[J].中国循证医学心血管医学杂志,2016;8(12):1491-2.
2 吴丹,杨胜利,路靖,等.冠心病患者支架术后根据检测药物代谢酶CYP2C19基因调整抗血小板治疗的价值[J].中国循环杂志,2015;30(3):216-8.
3 Musallam A,Orvin K,Perl L,et al.Effect of modifying antiplatelet treatment to ticagrelor in high-risk coronary patients with low response to clopidogrel(MATTIS)[J].Can J Cardiol,2016;32(10):1246.
4 Angiolillo DJ,Franchi F,Waksman R,et al.Effects of ticagrelor versus clopidogrel in troponin negative patients with low-risk ACS undergoing Ad Hoc PCI[J].J Am Coll Cardiol,2016;67(6):603-13.
5 Gurbel PA,Bliden KP,Butler K,et al.Response to ticagrelor in clopidogrel nonresponders and responders and effect of Switching therapies:the RESPOND study[J].Circulation,2010;121(10):1188-99.
6 Mehran R,Rao SV,Bhatt DL,et al.Standardized bleeding definitions for cardiovascular clinical trials:a consensus report from the Bleeding Academic Research Consortium[J].Circulation,2011;123(23):2736-47.
7 Abdel-Wahab M,Baev R,Dieker P,et al.Long-term clinical outcome of rotational atherectomy followed by drug-eluting stent implantation in complex calcified coronary lesions[J].Catheter Cardiovasc Interv,2013;81(2):285-91.
8 Wisman PP,Roest M,Asselbergs FW,et al.Platelet-reactivity tests identify patients at risk of secondary cardiovascular events:asystematic review and meta-analysis[J].J Thromb Haemost,2014;12(5):736-47.
9 Wen C,Xu H.The new strategy for modulating dyslipidemia:Consideration From updated understanding on high-density lipoprotein[J].Chin J Integr Med,2011;17(6):467-70.
10 唐云.氯吡格雷对PCI患者血小板功能状态及血流变的影响[J].北方药学,2017;14(1):103-4.
11 Abtahian F,Yonetsu T,Vergallo R,et al.Ticagrelor immediately prior to stenting is associated with smaller residual thrombus in patients with acute coronary syndrome[J].Int J Cardiol,2013;168(3):3099-101.
12 梁茜,张健瑜,杨希立,等.急性冠脉综合征合并糖尿病患者经皮冠脉介入术后替格瑞洛与氯吡格雷的疗效比较[J].中国医科大学学报,2016;45(2):145-7.
13 Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology(ESC),Steg PG,James SK,et al.ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation[J].Eur Heart J,2012;33(20):2569-619.
14 Van Haren RM,Valle EJ,Thorson CM,et al.Hypercoagulability and other risk factors in trauma intensive care unit patients with venousthromboembolism[J].J Trauma Acute Care Surg,2014;76(2):443-9.
15 于洪伟,刘奇峰,王玉亭,等.骨桥蛋白和基质金属蛋白酶-9对经皮冠状动脉介入治疗后支架内再狭窄的诊断价值[J].中国循环杂志,2015;30(7):635-7.
16 Skorko A,Thomas M,Mumford A,et al.Research protocol for platelets in out-of-hospital cardiac arrest:an observational,case-controlled,feasibility study to assess coagulation and platelet function abnormalities with ROTEM following out-of-hospital cardiac arrest(PoHCAR)[J].BMJ Open,2017;7(7):e015663.
17 Nguyen PA,Heggermont WA,Vanhaverbeke M,et al.Leptin-adiponectin ratio in pre-diabetic patients undergoing percutaneous coronary intervention[J].Acta Cardiol,2015;70(6):640-6.
18 Bliden KP,Tantry US,Storey RF,et al.The effect of ticagrelor versus clopidogrel on high on-treatment platelet reactivity:combined analysis of the ONSET/OFFSET and RESPOND studies[J].Am Heart J,2011;162(1):160-5.
19 冯春艳,苏东辉,于军.替格瑞洛对冠心病患者经皮冠状动脉介入治疗术后冠脉微循环功能的影响[J].血栓与止血,2016;22(5):507-10.
20 刘晓刚,胡立群,刘玉峰,等.替格瑞洛与氯吡格雷对急性非ST段抬高型心肌梗死患者经皮冠状动脉介入术后炎症因子的影响[J].中国临床药理学杂志,2016;32(9):789-91.
21 张明亮,沈玉华,张立敏,等.替格瑞洛对急性ST段抬高型心肌梗死急诊经皮冠状动脉介入患者血小板聚集率及QT离散度的影响[J].中国老年学杂志,2016;36(15):3667-9.
22 Hansson EC,Jidéus L,berg B,et al.Coronary artery bypass grafting-related bleeding complications in patients treated with ticagrelor or clopidogrel:a nationwide study[J].Eur Heart J,2016;37(2):189-97.
23 Hansson EC,Rexius H,Dellborg M,et al.Coronary artery bypass grafting-related bleeding complications in real-life acute coronary syndrome patients treated with clopidogrel or ticagrelor[J].Eur JCardiothorac Surg,2014;46(4):699-705.
24 Kohli P,Wallentin L,Reyes E,et al.Reduction in first and recurrent cardiovascular events with ticagrelor compared with clopidogrel in the PLATO Study[J].Circulation,2013;127(6):673-80.
25 Di Nicolantonio JJ,Tomek A.In activations,deletions,non-adjudications,and downgrades of clinical endpoints on ticagrelor:serious concerns over the reliability of the PLATO trial[J].Int J Cardiol,2013;168(4):4076-80.
26 Velders MA,Abtan J,Angiolillo DJ,et al.Safety and efficacy of ticagrelor and clopidogrel in primary percutaneous coronary intervention[J].Heart,2016;102(8):617-25.
27 刘然,师树田,索曼,等.对氯吡格雷低反应患者换用替格瑞洛后的有效性与安全性评价[J].中国介入心脏病学杂志,2014;22(1):12-5.
28 Ohman J,Kudira R,Albinsson S,et al.Ticagrelor induces adenosine triphosphate release from human red blood cells[J].Biochem Biophys Res Commun,2012;418(4):754-8.
29 白艳艳,史骏,刘成,等.不同抗血小板药物在ACS患者PCI术后氯吡格雷低反应性中的疗效及安全性[J].中国循证医学心血管医学杂志,2016;8(12):1491-2.