急性缺血性卒中静脉溶栓后早期抗血小板治疗的研究现状与展望

doi:10.3969/j.issn.1673-5765.2025.08.014

摘要/Abstract

摘要： 静脉溶栓治疗是急性缺血性卒中患者恢复脑血流灌注最主要的措施之一，目前急性缺血性卒中相关诊疗指南多建议在静脉溶栓后24 h后启动抗血小板治疗。然而，研究显示急性缺血性卒中患者静脉溶栓后至启动二级预防前，仍有症状加重和病情反复的风险。针对静脉溶栓后仍然呈现病情进展的急性缺血性卒中患者，若早期启动包括抗血小板治疗在内的二级预防，有望改善其预后。本文对近年来有关急性缺血性卒中患者静脉溶栓后24 h内启用抗血小板治疗的相关研究进行综述，以期为缺血性卒中患者溶栓后的治疗策略提供参考。

文章导读： 本文论述了急性缺血性卒中患者静脉溶栓后早期抗血小板治疗的可行性、安全性与有效性，并将其归纳为具体意见，以期为临床实践提供参考。

关键词: 急性缺血性卒中; 静脉溶栓治疗; 阿替普酶; 早期抗血小板治疗; 替罗非班

Abstract: Intravenous thrombolytic therapy has become the primary measure for restoring cerebral blood perfusion in patients with acute cerebral infarction. Guidelines recommend the use of antiplatelet drugs 24 hours after the end of intravenous thrombolytic therapy in patients with acute cerebral infarction. However, studies indicate that patients with acute cerebral infarction remain at risk of symptom aggravation and disease recurrence between intravenous thrombolysis and secondary prevention initiation. For patients with acute cerebral infarction who still show disease progression after intravenous thrombolysis, early initiation of secondary prevention, including antiplatelet therapy, is expected to improve their prognosis. This article reviews the relevant studies on antiplatelet therapy initiation within 24 hours after intravenous thrombolysis in patients with acute cerebral infarction in recent years, aiming to provide a reference for the treatment of patients with cerebral infarction after thrombolysis.

Key words: Acute cerebral infarction; Intravenous thrombolytic therapy; Alteplase; Early antiplatelet therapy; Tirofiban

中图分类号:

李子恒, 刘毅. 急性缺血性卒中静脉溶栓后早期抗血小板治疗的研究现状与展望[J]. 中国卒中杂志, 2025, 20(8): 1042-1050.

LI Ziheng, LIU Yi. Current Status and Prospects of Early Antiplatelet Therapy after Intravenous Thrombolysis in Acute Ischemic Stroke[J]. Chinese Journal of Stroke, 2025, 20(8): 1042-1050.

参考文献

[1] KRISHNAMURTHI R V，IKEDA T，FEIGIN V L. Global，regional and country-specific burden of ischaemic stroke，intracerebral haemorrhage and subarachnoid haemorrhage：a systematic analysis of the global burden of disease study 2017[J]. Neuroepidemiology，2020，54（2）：171-179.
[2] AZIZ Y N，KHATRI P. Intravenous thrombolysis to dissolve acute stroke thrombi：reflections on the past decade[J]. Stroke，2024，55（1）：186-189.
[3] KRASTEV G，MAKO M，ŠTEVKOVÁ Z，et al. Analysis of safety and efficacy of the early initiation of antithrombotic secondary prevention in patients treated with intravenous thrombolysis for acute ischemic stroke[J/OL]. J Clin Med，2024，13（9）：2710[2025-05-10]. https://doi.org/10.3390/jcm13092710.
[4] KOSTIS J B，DOCKENS R C，THADANI U，et al. Comparison of pharmacokinetics of lanoteplase and alteplase during acute myocardial infarction[J]. Clin Pharmacokinet，2002，41（6）：445-452.
[5] GLUND S，HOEFLER J，LANG B，et al. Bioequivalence of intravenous alteplase from two different manufacturing processes in healthy male volunteers：results from a two-stage，adaptive-design study[J]. Clin Pharmacokinet，2023，62（7）：1023-1030.
[6] KRAMER A H，JENNE C，HOLODINSKY J K，et al. Pharmacokinetics and pharmacodynamics of tissue plasminogen activator administered through an external ventricular drain[J]. Neurocrit Care，2015，23（3）：386-393.
[7] CHEN Z M，SANDERCOCK P，PAN H C，et al. Indications for early aspirin use in acute ischemic stroke ：a combined analysis of 40 000 randomized patients from the Chinese acute stroke trial and the international stroke trial[J]. Stroke，2000，31（6）：1240-1249.
[8] SAQQUR M，MOLINA C A，SALAM A，et al. Clinical deterioration after intravenous recombinant tissue plasminogen activator treatment：a multicenter transcranial Doppler study[J]. Stroke，2007，38（1）：69-74.
[9] 孙宜飞，张辉，刘彬，等. 急性缺血性卒中尿激酶静脉溶栓后早期应用替罗非班的疗效及对血小板相关参数的影响[J]. 川北医学院学报，2021，36（2）：197-200.
SUN Y F，ZHANG H，LIU B，et al. Effect of tirofiban on acute ischemic stroke after intravenous thrombolysis with urokinase and its effect on platelet related parameters[J]. Journal of North Sichuan Medical College，2021，36（2）：197-200.
[10] GONG L H，LIU M，ZENG T，et al. Crystal structure of the Michaelis complex between tissue-type plasminogen activator and plasminogen activators inhibitor-1[J]. J Biol Chem，2015，290（43）：25795-25804.
[11] 梁峰，胡大一. 替奈普酶（TNK-tPA）[J]. 临床药物治疗杂志，2003，1（1）：58-60.
LIANG F，HU D Y. Tenecteplase（TNK-tPA）[J]. Clinical Medication Journal，2003，1（1）：58-60.
[12] GU Y，XU C，ZHANG Z，et al. Association between infarct location and haemorrhagic transformation of acute ischaemic stroke after intravenous thrombolysis[J/OL]. Clin Radiol，2024，79（3）：e401-e407[2025-05-10]. https://doi.org/10.1016/j.crad.2023.11.024.
[13] 刘丽萍，陈玮琪，段婉莹，等. 中国脑血管病临床管理指南（节选版）——缺血性脑血管病临床管理[J]. 中国卒中杂志，2019，14（7）：709-726.
LIU L P，CHEN W Q，DUAN W Y，et al. Chinese Stroke Association guidelines for clinical management of cerebrovascular diseases（excerpt）—clinical management of ischemic cerebrovascular diseases[J]. Chin J Stroke，2019，14（7）：709-726.
[14] PENG T J，SCHWAMM L H，FONAROW G C，et al. Contemporary prestroke dual antiplatelet use and symptomatic intracerebral hemorrhage risk after thrombolysis[J]. JAMA Neurol，2024，81（7）：722-731.
[15] 张心邈，王春娟，杨昕，等. 发病前口服抗栓药物对急性缺血性卒中患者静脉溶栓安全性的影响研究[J]. 中国卒中杂志，2021，16（11）：1110-1114.
ZHANG X M，WANG C J，YANG X，et al. Safety of intravenous thrombolysis in acute ischemic stroke patients with antithrombotic therapy before stroke onset[J]. Chin J Stroke，2021，16（11）：1110-1114.
[16] XIAN Y，FEDERSPIEL J J，GRAU-SEPULVEDA M，et al. Risks and benefits associated with prestroke antiplatelet therapy among patients with acute ischemic stroke treated with intravenous tissue plasminogen activator[J]. JAMA Neurol，2016，73（1）：50-59.
[17] LUO S Y，ZHUANG M，ZENG W T，et al. Intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy：a systematic review and meta‐analysis of 19 studies[J/OL]. J Am Heart Assoc，2016，5（5）：e003242[2025-05-10]. https://doi.org/10.1161/JAHA.116.003242.
[18] 龚汉贤，李飞，罗丽霞，等. 轻型缺血性脑卒中静脉溶栓后24 h内抗血小板聚集治疗的研究[J]. 卒中与神经疾病，2019，26（1）：43-46.
GONG H X，LI F，LUO L X，et al. Early administration of antiplatelet treatment after intravenous thrombolysis for mild ischemic stroke[J]. Stroke and Nervous Diseases，2019，26（1）：43-46.
[19] 宋景阳. 轻型缺血性脑卒中静脉溶栓后早期进行抗血小板聚集治疗的疗效[J]. 系统医学，2021，6（19）：70-72.
SONG J Y. Efficacy of early antiplatelet aggregation therapy after intravenous thrombolysis in mild ischemic stroke[J]. Systems Medicine，2021，6（19）：70-72.
[20] 刘颖颇. 轻型缺血性脑卒中静脉溶栓后24 h内抗血小板聚集治疗的研究[J]. 当代医学，2020，26（7）：47-49.
LIU Y P. Study on antiplatelet aggregation therapy within 24 hours after intravenous thrombolysis of mild ischemic stroke[J]. Contemporary Medicine，2020，26（7）：47-49.
[21] ZHANG Y，WANG J L，MA Z X，et al. Prospective pilot study of tirofiban in progressive stroke after intravenous thrombolysis[J/OL]. Front Neurol，2022，13：982684[2025-05-10]. https://doi.org/10.3389/fneur.2022.982684.
[22] WU C J，SUN C H，WANG L J，et al. Low-dose tirofiban treatment improves neurological deterioration outcome after intravenous thrombolysis[J]. Stroke，2019，50（12）：3481-3487.
[23] 李艺，余聪聪. 探讨脑梗死静脉溶栓后早期使用替罗非班对进展性脑梗死的影响[J]. 中国现代药物应用，2024，18（14）：74-76.
LI Y，YU C C. The effect of early use of tirofiban on progressive cerebral infarction after intravenous thrombolysis in patients with cerebral infarction[J]. Chin J Mod Drug Appl，2024，18（14）：74-76.
[24] LIU Y Z，LI S Y，HAO D D，et al. Clinical safety and possible efficacy of tirofiban in combination with intravenous thrombolysis by recombinant tissue plasminogen activator for early treatment of capsular warning syndrome（CWS）[J/OL]. Front Neurosci，2022，16：1026127[2025-05-10]. https://doi.org/10.3389/fnins.2022.1026127.
[25] 宋杰. 阿替普酶静脉溶栓后早期应用替罗非班对脑梗死患者血小板和神经缺损的影响[J]. 医药论坛杂志，2022，43（8）：36-39.
SONG J. Effect of early application of tirofiban after alteplase intravenous thrombolysis on platelet and nerve defects in patients with cerebral infarction[J]. J Medical Forum，2022，43（8）：36-39.
[26] LIU J，SHI Q Y，SUN Y，et al. Efficacy of tirofiban administered at different time points after intravenous thrombolytic therapy with alteplase in patients with acute ischemic stroke[J]. J Stroke Cerebrovasc Dis，2019，28（4）：1126-1132.
[27] AMARO S，LLULL L，URRA X，et al. Risks and benefits of early antithrombotic therapy after thrombolytic treatment in patients with acute stroke[J/OL]. PloS One，2013，8（8）：e71132[2025-05-10]. https://doi.org/10.1371/journal.pone.0071132.
[28] TODA Y，KATSURA K I，SAITO M，et al. The effect of cilostazol and aspirin pre-treatment against subsequent transient focal cerebral ischemia in rat[J]. Neurol Res，2014，36（11）：1011-1019.
[29] GOTOH F，TOHGI H，HIRAI S，et al. Cilostazol stroke prevention study：a placebo-controlled double-blind trial for secondary prevention of cerebral infarction[J]. J Stroke Cerebrovasc Dis，2000，9（4）：147-157.
[30] SHINOHARA Y，KATAYAMA Y，UCHIYAMA S，et al. Cilostazol for prevention of secondary stroke（CSPS 2）：an aspirin-controlled，double-blind，randomised non-inferiority trial[J]. Lancet Neurol，2010，9（10）：959-968.
[31] 奚亮亮. 尿激酶静脉溶栓联合早期双抗血小板在老年急性缺血性脑卒中急救中的应用[J]. 罕少疾病杂志，2023，30（10）：8-10.
XI L L. Urinary kinase intravenous thrombolysis combined with early dual antiplatelet in senile acute ischemic stroke[J]. Journal of Rare and Uncommon Diseases，2023，30（10）：8-10.
[32] 慕鹏莺，刘晓荷，王梦碧，等. 早期应用替罗非班对急性缺血性卒中尿激酶静脉溶栓后的疗效及对血小板指标的影响[J]. 血栓与止血学，2022，28（1）：54-55，58.
MU P Y，LIU X H，WANG M B，et al. The effect of early application of tirofiban on urokinase intravenous thrombolysis of acute ischemic stroke and its influence on platelet indexes[J]. Chinese Journal of Thrombosis and Hemostasis，2022，28（1）：54-55，58.
[33] JAUCH E C，SAVER J L，ADAMS H P，Jr，et al. 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（3）：870-947.
[34] JI X M，LI K，LI W B，et al. The effects of blood pressure and urokinase on brain injuries after experimental cerebral infarction in rats[J]. Neurol Res，2009，31（2）：204-208.
[35] BURGER K M，HOROWITZ D R. Thrombolytic treatment of acute cerebral infarction[J]. CNS Spectr，2005，10（7）：539-549.
[36] SUN F，LIU H，FU H X，et al. Comparative study of intravenous thrombolysis with rt-PA and urokinase for patients with acute cerebral infarction[J/OL]. J Int Med Res，2020，48（5）：300060519895352[2025-05-10]. https://doi.org/10.1177/0300060519895352.