Study on the efficacy and safety of aspirin combined with clopidogrel pretreatment before rt-PA intravenous thrombolysis in patients with cardioembolism

doi:10.3969/j.issn.1672-6731.2020.05.010

Abstract

Abstract:

Objective To investigate the efficacy and safety of aspirin combined with clopidogrel pretreatment before intravenous thrombolysis with rt-PA in patients with cardioembolism (CE). Methods Three hundred and thirteen patients with CE treated with rt-PA intravenous thrombolysis from July 2018 to July 2019 were admitted. Among them, 167 patients were pretreated with aspirin combined with clopidogrel before thrombolysis (pretreatment group), and 146 patients were not (control group). The short-term improvement of neurological function (1 h, 24 h and 7 d after thrombolysis) was evaluated by National Institutes of Health Stroke Scale (NIHSS). The long-term prognosis (90 d after onset) was evaluated by modified Rankin Scale (mRS), and mortality and the incidence of intracranial hemorrhage (ICH) within 90 d after onset were recorded. Results The neurological function improvement rates in the pretreatment group at 1 h, 24 h and 7 d after intravenous thrombolysis were higher than those in control group[48.50% (81/167) vs. 32.19% (47/146), χ²=8.574, P=0.003; 57.49% (96/167) vs. 45.21% (66/146), χ²=4.704, P=0.030; 77.25% (129/167) vs. 63.01% (92/146), χ²=7.602, P=0.006]. The incidence of ICH after thrombolysis[3.59% (6/167) vs. 3.42% (5/146); χ²=0.006, P=0.936], mortality[0.60% (1/167) vs. 0.68% (1/146); Fisher's exact probability:P=1.000] and the rate of good prognosis within 90 d after onset[80.84% (135/167) vs. 74.66% (109/146); χ²=1.732, P=0.188] between 2 groups were no significant difference. Conclusions Aspirin combined with clopidogrel pretreatment before intravenous thrombolysis can improve early neurological function in patients with CE, and does not increase the risk of ICH. It is safe and effective for clinical application.

Key words: Stroke, Tissue plasminogen activator, Thrombolytic therapy, Platelet aggregation inhibitors

摘要：

目的探讨心源性栓塞患者rt-PA静脉溶栓前阿司匹林联合氯吡格雷双联抗血小板预处理的有效性和安全性。方法 2018年7月至2019年7月共313例心源性栓塞患者均接受rt-PA静脉溶栓治疗，溶栓前予阿司匹林联合氯吡格雷预处理167例（预处理组），未服药146例（对照组），采用美国国立卫生研究院卒中量表（NIHSS）评价近期（溶栓后1 h、24 h和7 d）神经功能改善，改良Rankin量表（mRS）评价远期（发病后90 d）预后，并记录颅内出血发生率和病死率。结果预处理组患者静脉溶栓后1 h[48.50%（81/167）对32.19%（47/146）；χ²=8.574，P=0.003]、24 h[57.49%（96/167）对45.21%（66/146）；χ²=4.704，P=0.030]和7 d[77.25%（129/167）对63.01%（92/146）；χ²=7.602，P=0.006]神经功能改善率均高于对照组，而两组溶栓后颅内出血发生率[3.59%（6/167）对3.42%（5/146）；χ²=0.006，P=0.936]、病死率[0.60%（1/167）对0.68%（1/146）；Fisher确切概率法：P=1.000]和发病后90 d预后良好率[80.84%（135/167）对74.66%（109/146）；χ²=1.732，P=0.188]差异均无统计学意义。结论 rt-PA静脉溶栓前阿司匹林联合氯吡格雷双联抗血小板预处理可以改善心源性栓塞患者早期神经功能，且不增加颅内出血和死亡风险，临床应用安全、有效。

关键词: 卒中, 组织型纤溶酶原激活物, 血栓溶解疗法, 血小板聚集抑制剂

LI Chen-hua, ZHANG Shan-shan, WANG Yu-xin, CHEN Yan, ZHANG Chen-hao, ZHANG Pei-lan. Study on the efficacy and safety of aspirin combined with clopidogrel pretreatment before rt-PA intravenous thrombolysis in patients with cardioembolism[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2020, 20(5): 427-433.

李晨华, 张闪闪, 王育新, 陈岩, 张辰昊, 张佩兰. 心源性栓塞患者rt-PA静脉溶栓前阿司匹林联合氯吡格雷预处理的有效性和安全性分析[J]. 中国现代神经疾病杂志, 2020, 20(5): 427-433.

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https://journal11.magtechjournal.com/cjcnn/EN/Y2020/V20/I5/427

References

[1] Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL; American Heart Association Stroke Council. 2018 guidelines for the early management of patients with acute ischemic stroke:a guideline for healthcare professionals from the American Heart Association/American Stroke Association[J]. Stroke, 2018, 49:E46-110.
[2] National Health Commission Stroke Prevention and Treatment Expert Committee Atrial Fibrillation Stroke Prevention and Treatment Professional Committee, Chinese Medical Association Cardiac Electrophysiology and Pacing Branch, Chinese Medical Association Cardiology Professional Committee. Guidline on prevention and treatment of cardiogenic stroke (2019)[J]. Zhonghua Xin Lü Shi Chang Xue Za Zhi, 2019, 23:463-484.[国家卫生健康委员会脑卒中防治专家委员会房颤卒中防治专业委员会, 中华医学会心电生理和起搏分会, 中国医师协会心律学专业委员会. 中国心源性卒中防治指南(2019)[J]. 中华心律失常学杂志, 2019, 23:463-484.]
[3] Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O'Donnell MJ, Sacco RL, Connolly SJ; Cryptogenic Stroke/ESUS International Working Group. Embolic strokes of undetermined source:the case for a new clinical construct[J]. Lancet Neurol, 2014, 13:429-438.
[4] National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke[J]. N Engl J Med, 1995, 333:1581-1587.
[5] Molina CA, Montaner J, Abilleira S, Arenillas JF, Ribó M, Huertas R, Romero F, Alvarez-Sabín J. Time course of tissue plasminogen activator induced recanalizatoin in actue cardio-embolic stroke:a case control study[J]. Stroke, 2001, 32:2821-2827.
[6] IST-3 Collaborative Group; Sandercock P, Wardlaw JM, Lindley RI, Dennis M, Cohen G, Murray G, Innes K, Venables G, Czlonkowska A, Kobayashi A, Ricci S, Murray V, Berge E, Slot KB, Hankey GJ, Correia M, Peeters A, Matz K, Lyrer P, Gubitz G, Phillips SJ, Arauz A. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischacmicstroke (the third inerantional stroke trial[IST-3]):a randomized controlled trial[J]. Lancet, 2012, 379:2352-2363.
[7] Tang S, Yan LR, Sun YH, Chen J, Hu HT. Effectiveness and safety of thrombolytic therapy for cardiogenic cerebral embolism by intravenous recombinant tissue plasminogen activator[J]. Zhongguo Zu Zhong Za Zhi, 2013, 8:360-367.[唐澍, 闫立荣, 孙玉衡, 陈捷, 胡洪涛. 重组组织型纤溶酶原激活剂治疗心源性脑栓塞的疗效与安全性分析[J]. 中国卒中杂志, 2013, 8:360-367.]
[8] Lu XL. Observation on the efficacy of recombinant tissue plasminogen activator in the treatment of cardiogenic cerebral embolism[J]. Zhongguo Shi Yong Shen Jing Ji Bing Za Zhi, 2016, 19:110-112.[陆晓莲. 重组组织型纤溶酶原激活剂治疗心源性脑栓塞的疗效观察[J]. 中国实用神经疾病杂志, 2016, 19:110-112.]
[9] Fu ML, Xiao XL, Dai WZ, Ye YA, Ruan ZF, Wang SH, He WQ. Observation on the efficacy of intravenous thrombolysis with recombinant tissue plasminogen activator in the treatment of cardiogenic cerebral embolism[J]. Zhong Xi Yi Jie He Xin Nao Xue Guan Bing Za Zhi, 2016, 14:772-774.[傅懋林, 肖雪玲, 戴为正, 叶迎安, 阮志芳, 王双虎, 何文钦. 重组组织型纤溶酶原激活剂静脉溶栓治疗心源性脑栓塞疗效观察[J]. 中西医结合心脑血管病杂志, 2016, 14:772-774.]
[10] Zangerle A, Kiechl S, Spiegel M, Furtner M,Knoflach M, Werner P, Mair A, S, Wille G, Schmidauer C, Gautsch K, Gotwald T, Felber Poewe W, Willeit J. Recanalization after thrombolysis in stroke patients:predictors and prognostic implications[J]. Neurology, 2007, 68:39-44.
[11] Neurology Branch of Chinese Medical Association, Group of Cerebrovascular Diseases of Neurology Branch of Chinese Medical Association. Consensus on diagnosis and treatment of hemorrhagic transformation after acute ischemic stroke in China 2019[J]. Zhonghua Shen Jing Ke Za Zhi, 2019, 52:252-265.[中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组. 中国急性脑梗死后出血转化诊治共识2019[J]. 中华神经科杂志, 2019, 52:252-265.]
[12] Saposnik G, Gladstone D, Raptis R, Zhou L, Hart RG; Investigators of the Registry of the Canadian Stroke Network (RCSN) and the Stroke Outcomes Research Canada (SORCan) Working Group. Atrial fibrillation in ischemic stroke:predicting response to thrombolysis and clinical outcomes[J]. Stroke, 2013, 44:99-104.
[13] Seet RC, Zhang Y, Wijdicks EF, Rabinstein AA. Relationship between chronic atrial fibrillation and worse outcomes in stroke patients after intravenous thrombolysis[J]. Arch Neurol, 2011, 68:1454-1458.
[14] Neurology Branch of Chinese Medical Association, Group of Cerebrovascular Diseases of Neurology Branch of Chinese Medical Association. Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018[J]. Zhonghua Shen Jing Ke Za Zhi, 2018, 51:666-682.[中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组. 中国急性缺血性脑卒中诊治指南2018[J]. 中华神经科杂志, 2018, 51:666-682.]
[15] Larrue V, von Kummer RR, Müller A, Bluhmki E. Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator:a secondary analysis of the european-australasian acute stroke study (ECASS Ⅱ[)J]. Stroke, 2001, 32:438-441.
[16] de los Ríos la Rosa F, Khoury J, Kissela BM, Flaherty ML, Alwell K, Moomaw CJ, Khatri P, Adeoye O, Woo D, Ferioli S, Kleindorfer DO. Eligibility for intravenous recombinant tissue-type plasminogen activator within a population:the effect of the european cooperative acute stroke study (ECASS) Ⅲ trial[J]. Stroke, 2012, 43:1591-1595.
[17] Jauch EC, Saver JL, Adams HP Jr, Bruno A, Connors JJ, Demaerschalk BM, Khatri P, McMullan PW Jr, Qureshi AI, Rosenfield K, Scott PA, Summers DR, Wang DZ, Wintermark M, Yonas H; American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Peripheral Vascular Disease, Council on Clinical Cardiology. Guidelines for the early management of patients with acute ischemic stroke:a guideline for healthcare professionals from the American Heart Association/American Stroke Association[J]. Stroke, 2013, 44:870-947.
[18] Hack W, Kaste M, Fieshchi C, Toni D, Lesaffre E, von Kummer R, Boysen G, Bluhmki E, Höxter G, Mahagne MH. The ECASS study grope intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke:the European Cooperative Acute Stroke Study (ECASS)[J]. JAMA, 1995, 274:1017-1025.
[19] Yamaji K, Fujimoto S, Yutani C, Hashimoto T, Nakamura S. Is the site of thrombus formation in the left atrial appendage associated with the risk of cerebral embolism[J]? Cardiology, 2002, 97:104-110.
[20] Molina CA, Ribo M, Rubiera M, Santamarina E, Delgado-Mederos R, Maisterra O. TNK induces faster recanalization and tPA:the TNK-tPA reperfusion stroke study[J]. Stroke, 2008, 39:563.
[21] Berger C, Fiorelli M, Steiner T, Schäbitz WR, Bozzao L, Bluhmki E, Hacke W, von Kummer R. Hemorrhagic transformation of ischemic brain tissue:asymptomatic or symptomatic[J]? Stroke, 2001, 32:1330-1335.
[22] Cardiogenic brain embolism:the second report of the cerebral embolism task force[J]. Arch Neurol, 1989, 46:727-743.
[23] Lao QK, Wang DC. Advances of intravenous thrombolytic therapy in hyperacute cardiogenic cerebral embolism[J]. Zhongguo Lin Chuang Xin Yi Xue, 2015, 8:583-586.[劳全坤, 王大成. 心源性脑栓塞超急性期静脉溶栓治疗的研究进展[J]. 中国临床新医学, 2015, 8:583-586.]
[24] von Klemperer A, Bateman K, Owen J, Bryer A. Thrombolysis risk prediction:applying the SITS-SICH and SEDAN scores in South African patients[J]. Cardiovasc J Afr, 2014, 25:224-227.
[25] Shi PS, Chen SR, Zhou HN. Dynamic observation and follow-up of white microthrombus in microcirculation of ischemic cerebrovascular disease[J]. Wei Xun Huan Xue Za Zhi, 1997, 7:15-16.[史培圣, 陈士荣, 周海宁. 缺血性脑血管病微循环白色微血栓动态观察和追踪随访[J]. 微循环学杂志, 1997, 7:15-16.]
[26] Stroke Prevention Engineering Committee of National Health and Family Planning Commission, Professional Committee of Cardiovascular and Cerebrovascular Diseases of Chinese Geriatrics Association. Chinese expert consensus on perioperative application of antiplatelet drugs in patients with ischemic stroke 2016[J]. Zhonghua Yi Xue Za Zhi, 2016, 96:3443-3453.[国家卫生计生委脑卒中防治工程委员会, 中国老年学学会心脑血管病专业委员会. 缺血性脑卒中患者围手术期抗血小板药物应用中国专家共识2016[J]. 中华医学杂志, 2016, 96:3443-3453.]
[27] Qin F, Cai H. Advances in drug treatment of acute ischemic stroke[J]. Yi Nan Bing Za Zhi, 2015, 14:870-876.[秦峰, 蔡辉. 急性缺血性卒中的药物治疗进展[J]. 疑难病杂志, 2015, 14:870-876.]
[28] Siebler M, Hennerici MG, Schneider D, Gerhard M, von Reutern, Seitz RJ, Joachim R, Witte OW, Hamann G, Junghans U, Villringer A, Fiebach JB. Safety of tirofiban in acute ischemic stroke:the Sa TIS trial[J]. Stroke, 2011, 42:2388-2392.
[29] Song NN. Research for protective effect of pretreatment of bay aspirin on focal cerebral ischemia reperfusion damage in SD rat with hyperglycemia[D]. Dalian:Dalian Yi Ke Da Xue, 2006.[宋妮娜. 拜阿司匹灵预处理对高血糖SD大鼠局部脑缺血再灌注损伤的保护作用的研究[D]. 大连:大连医科大学, 2006.]
[30] Chen M. The role of miR-145 in the anti-proliferation and anti-inflammation effects of aspirin on VSMCs[D]. Changsha:Zhong Nan University, 2014.[陈敏. miR-145介导阿司匹林抗血管平滑肌细胞增殖及抗炎作用的研究[D]. 长沙:中南大学, 2014.]
[31] Salimi S, Lewis JP, Yerges-Armstrong LM, Mitchell BD, Saeed F, O'Connell JR, Perry JA, Ryan KA, Shuldiner AR, Parsa A. Clopidogrel improves skin microcirculatory endothelial function in persons with heightened platelet aggregation[J]. J Am Heart Assoc, 2016, 5:E003751.
[32] Yuan S, Yan J. Observation on the efficacy of clopidogrel and aspirin combined with alteplase intravenous thrombolysis in the treatment of acute myocardial infarction[J]. Zhongguo Xian Dai Yi Yao Za Zhi, 2014, 16:67-68.[袁森, 闫洁. 氯吡格雷、阿司匹林联合阿替普酶静脉溶栓治疗急性心肌梗死疗效观察[J]. 中国现代医药杂志, 2014, 16:67-68.]
[33] Uyttenboogaart M, Koch MW, Koopman K, Vroomen PC, De Keyser J, Luijckx GJ. Safety of antiplatelet therapy prior to intravenous thrombolysis in acute ischemic stroke[J]. Arch Neurol, 2008, 65:607-611.
[34] Sun C, Song BL, Jiang CL, Zou JJ. Effect of antiplatelet pretreatment on safety and efficacy outcomes in acute ischemic stroke patients after intravenous thrombolysis:a systematic review and meta-analysis[J]. Exppert Rev Neurother, 2019, 19:349-358.
[35] Pan X, Zhu Y, Zheng D, Liu Y, Yu F, Yang J. Prior antiplatelet agent use and outcomes after intravenous thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke:a meta-analysis of cohort studies and randomized controlled trials[J]. Int J Stroke, 2015, 10:317-323.
[36] Qu D, Li WD, Li LF, Fu B, Zhang XF. Efficacy and safety of intravenous thrombolysis after oral aspirin pretreatment in patients with acute ischemic stroke[J]. Hang Kong Hang Tian Yi Xue Za Zhi, 2018, 29:533-534.[曲典, 李文娣, 李兰凤, 付博, 张雪凤. 急性缺血性脑卒中患者口服阿司匹林预处理后静脉溶栓的有效性与安全性观察[J]. 航空航天医学杂志, 2018, 29:533-534.]
[37] Kellert L, Hametner C, Rohde S, Bendszus M, Hacke W, Ringleb P, Stampfl S. Endovascular stroke therapy:tirofiban is associated with risk of fatal intracerebral hemorrhage and poor outcome[J]. Stroke, 2013, 44:1453-1455.

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