从起步到辉煌——中国卒中临床研究发展20年

doi:10.3969/j.issn.1673-5765.2025.05.001

摘要/Abstract

摘要： 卒中是造成我国居民残疾和死亡的主要疾病之一，给医疗系统带来了巨大负担。循证医学研究为卒中诊疗提供了可靠的数据指导，显著降低了卒中的残疾率与死亡率。近20年来，中国临床工作者和科研人员围绕卒中诊疗的各个环节，在急性缺血性卒中再灌注治疗、卒中二级预防、脑细胞保护、血管内治疗围手术期管理、卒中诊疗质量控制与管理等重要及热点领域贡献了诸多宝贵的循证医学证据，在卒中临床研究领域发挥着越来越重要的作用。本文简要回顾了我国卒中循证医学研究的发展历程，概述了中国研究者在卒中诊疗循证实践方面的贡献与成就，并对下一阶段的卒中研究进行了展望。

关键词: 循证医学; 脑血管病; 缺血性卒中; 出血性卒中; 再灌注; 静脉溶栓; 血管内治疗; 二级预防

Abstract: Stroke is one of the major diseases causing disability and death in Chinese residents, placing a significant burden on the healthcare system. Evidence-based medical research provides reliable data to guide stroke diagnosis and treatment, significantly reducing stroke-related disability and mortality rates. Over the past two decades, Chinese clinicist and researchers have played an increasingly prominent role in clinical research on stroke. Focusing on various aspects of stroke diagnosis and treatment, they have contributed valuable evidence-based medical evidence in major and hot fields such as reperfusion therapy for acute ischemic stroke, secondary prevention of stroke, brain cytoprotection, application of new devices and techniques, perioperative management of endovascular treatment, and quality control and management of stroke diagnosis and treatment. This article briefly reviews the development history of evidence-based medicine for stroke in China, summarizes the contributions and achievements of Chinese researchers in evidence-based practice for stroke diagnosis and treatment, and looks forward to the next phase of stroke research.

Key words: Evidence-based medicine; Cerebrovascular disease; Ischemic stroke; Hemorrhagic stroke; Reperfusion; Intravenous thrombolysis; Endovascular treatment; Secondary prevention

中图分类号:

熊云云, 王拥军. 从起步到辉煌——中国卒中临床研究发展20年[J]. 中国卒中杂志, 2025, 20(5): 519-528.

XIONG Yunyun, WANG Yongjun. From Inception to Excellence: Two Decades of Stroke Clinical Research in China[J]. Chinese Journal of Stroke, 2025, 20(5): 519-528.

参考文献

[1] International Stroke Trial Collaborative Group. The international stroke trial（IST）：a randomised trial of aspirin，subcutaneous heparin，both，or neither among 19 435 patients with acute ischaemic stroke[J]. Lancet，1997，349（9065）：1569-1581.
[2] CHEN Z M，CAST（Chinese Acute Stroke Trial）Collaborative Group. CAST：randomised placebo-controlled trial of early aspirin use in 20 000 patients with acute ischaemic stroke[J]. Lancet，1997，349（9066）：1641-1649.
[3] BARER D. Interpretation of IST and CAST stroke trials[J]. Lancet，1997，350（9075）：440.
[4] HUANG Y N，CHENG Y，WU J，et al. Cilostazol as an alternative to aspirin after ischaemic stroke：a randomised，double-blind，pilot study[J]. Lancet Neurol，2008，7（6）：494-499.
[5] HANKEY G J. Cilostazol shows promise as an alternative to aspirin for patients with ischaemic stroke[J]. Lancet Neurol，2008，7（6）：469-470.
[6] SACCO R L，DIENER H C，YUSUF S，et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke[J]. N Engl J Med，2008，359（12）：1238-1251.
[7] MIAO Z R，JIANG L D，WU H，et al. Randomized controlled trial of symptomatic middle cerebral artery stenosis：endovascular versus medical therapy in a Chinese population[J]. Stroke，2012，43（12）：3284-3290.
[8] MENG R，ASMARO K，MENG L，et al. Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis[J]. Neurology，2012，79（18）：1853-1861.
[9] WANG Y J，CUI L Y, JI X M，et al. The China national stroke registry for patients with acute cerebrovascular events：design，rationale，and baseline patient characteristics[J]. Int J Stroke，2011，6（4）：355-361.
[10] LI Z X，WANG C J，ZHAO X Q，et al. Substantial progress yet significant opportunity for improvement in stroke care in China[J]. Stroke，2016，47（11）：2843-2849.
[11] WANG Y J，JING J，MENG X，et al. The third China national stroke registry（CNSR-Ⅲ）for patients with acute ischaemic stroke or transient ischaemic attack：design，rationale and baseline patient characteristics[J]. Stroke Vasc Neurol，2019，4（3）：158-164.
[12] WANG Y J，WANG Y L，ZHAO X Q，et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack[J]. N Engl J Med，2013，369（1）：11-19.
[13] WANG Y J，LI S Y，PAN Y S，et al. Tenecteplase versus alteplase in acute ischaemic cerebrovascular events（TRACE-2）：a phase 3，multicentre，open-label，randomised controlled，non-inferiority trial[J]. Lancet，2023，401（10377）：645-654.
[14] MENG X，LI S Y，DAI H G，et al. Tenecteplase vs.
alteplase for patients with acute ischemic stroke：the ORIGINAL randomized clinical trial[J]. JAMA，2024，332（17）：1437-1445.
[15] LI S Y，GU H Q，LI H，et al. Reteplase versus alteplase for acute ischemic stroke[J]. N Engl J Med，2024，390（24）：2264-2273.
[16] LI S Y，GU H Q，FENG B Y，et al. Safety and efficacy of intravenous recombinant human prourokinase for acute ischaemic stroke within 4.5 h after stroke onset（PROST-2）：a phase 3，open-label，non-inferiority，randomised controlled trial[J]. Lancet Neurol，2025，24（1）：33-41.
[17] GU H Q，YANG X，WANG C J，et al. Clinical characteristics，management，and in-hospital outcomes in patients with stroke or transient ischemic attack in China[J/OL]. JAMA Netw Open，2021，4（8）：e2120745[2025-03-02]. https://doi.org/10.1001/jamanetworkopen.2021.20745.
[18] XIONG Y Y，CAMPBELL B C V，SCHWAMM L H，et al. Tenecteplase for ischemic stroke at 4.5 to 24 hours without thrombectomy[J]. N Engl J Med，2024，391（3）：203-212.
[19] CHENG X，HONG L，CHURILOV L，et al. Tenecteplase thrombolysis for stroke up to 24 hours after onset with perfusion imaging selection：the umbrella phase Ⅱa CHABLIS-T randomised clinical trial[J]. Stroke Vasc Neurol，2024，9（5）：551-559.
[20] LUO Z Y，ZHOU Y，HE Y D，et al. Treatment with intravenous alteplase in ischaemic stroke patients with onset time between 4.5 and 24 hours（HOPE）：protocol for a randomised，controlled，multicentre study[J]. Stroke Vasc Neurol，2024，9（3）：318-323.
[21] CHEN H S，CUI Y，ZHOU Z H，et al. Effect of argatroban plus intravenous alteplase vs. intravenous alteplase alone on neurologic function in patients with acute ischemic stroke：the ARAIS randomized clinical trial[J]. JAMA，2023，329（8）：640-650.
[22] XIONG Y Y，MENG X，JIN A M，et al. Prourokinase vs. standard care for patients with mild ischemic stroke：the PUMICE randomized clinical trial[J]. JAMA Neurol，2025，82（3）：258-266.
[23] LIU X F，DAI Q L，YE R D，et al. Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion（BEST）：an open-label，randomised controlled trial[J]. Lancet Neurol，2020，19（2）：115-122.
[24] TAO C R，NOGUEIRA R G，ZHU Y Y，et al. Trial of endovascular treatment of acute basilar-artery occlusion[J]. N Engl J Med，2022，387（15）：1361-1372.
[25] JOVIN T G，LI C H，WU L F，et al. Trial of thrombectomy 6 to 24 hours after stroke due to basilar-artery occlusion
[J]. N Engl J Med，2022，387（15）：1373-1384.
[26] HUO X C，MA G T，TONG X，et al. Trial of endovascular therapy for acute ischemic stroke with large infarct[J]. N Engl J Med，2023，388（14）：1272-1283.
[27] YANG P F，ZHANG Y W，ZHANG L，et al. Endovascular thrombectomy with or without intravenous alteplase in acute stroke[J]. N Engl J Med，2020，382（21）：1981-1993.
[28] ZI W J，QIU Z M，LI F L，et al. Effect of endovascular treatment alone vs. intravenous alteplase plus endovascular treatment on functional independence in patients with acute ischemic stroke：the DEVT randomized clinical trial[J]. JAMA，2021，325（3）：234-243.
[29] CHEN H S，CUI Y，ZHOU Z H，et al. Dual antiplatelet therapy vs. alteplase for patients with minor nondisabling acute ischemic stroke：the ARAMIS randomized clinical trial[J]. JAMA，2023，329（24）：2135-2144.
[30] WANG Y L，ZHAO X Q，LIN J X，et al. Association between CYP2C19 loss-of-function allele status and efficacy of clopidogrel for risk reduction among patients with minor stroke or transient ischemic attack[J]. JAMA，2016，316（1）：70-78.
[31] WANG Y J，MENG X，WANG A X，et al. Ticagrelor versus clopidogrel in CYP2C19 loss-of-function carriers with stroke or TIA[J]. N Engl J Med，2021，385（27）：2520-2530.
[32] GAO Y，CHEN W Q，PAN Y S，et al. Dual antiplatelet treatment up to 72 hours after ischemic stroke[J]. N Engl J Med，2023，389（26）：2413-2424.
[33] CHEN H S，CUI Y，WANG X H，et al. Clopidogrel plus aspirin vs. aspirin alone in patients with acute mild to moderate stroke：the ATAMIS randomized clinical trial[J]. JAMA Neurol，2024，81（5）：450-460.
[34] PAN Y S，MENG X，YUAN B S，et al. Indobufen versus aspirin in patients with acute ischaemic stroke in China（INSURE）：a randomised，double-blind，double-dummy，active control，non-inferiority trial[J]. Lancet Neurol，2023，22（6）：485-493.
[35] ZI W J，SONG J X，KONG W L，et al. Tirofiban for stroke without large or medium-sized vessel occlusion
[J]. N Engl J Med，2023，388（22）：2025-2036.
[36] ZHAO W B，LI S J，LI C H，et al. Effects of tirofiban on neurological deterioration in patients with acute ischemic stroke：a randomized clinical trial[J]. JAMA Neurol，2024，81（6）：594-602.
[37] LI J J，MENG X，SHI F D，et al. Colchicine in patients with acute ischaemic stroke or transient ischaemic attack（CHANCE-3）：multicentre，double blind，randomised，placebo controlled trial[J/OL]. BMJ，2024，385：e079061[2025-03-02]. https://doi.org/10.1136/bmj-2023-079061.
[38] HE J，ZHANG Y H，XU T，et al. Effects of immediate blood pressure reduction on death and major disability in patients with acute ischemic stroke：the CATIS randomized clinical trial[J]. JAMA，2014，311（5）：479-489.
[39] LIU L P，XIE X W，PAN Y S，et al. Early versus delayed antihypertensive treatment in patients with acute ischaemic stroke：multicentre，open label，randomised，controlled trial[J/OL]. BMJ，2023，383：e076448[2025-03-02]. https://doi.org/10.1136/bmj-2023-076448.
[40] GAO P，WANG T，WANG D M，et al. Effect of stenting plus medical therapy vs. medical therapy alone on risk of stroke and death in patients with symptomatic intracranial stenosis：the CASSISS randomized clinical trial[J]. JAMA，2022，328（6）：534-542.
[41] MA Y，WANG T，WANG H B，et al. Extracranial-intracranial bypass and risk of stroke and death in patients with symptomatic artery occlusion：the CMOSS randomized clinical trial[J]. JAMA，2023，330（8）：704-714.
[42] JIA B X，ZHANG X L，MA N，et al. Comparison of drug-eluting stent with bare-metal stent in patients with symptomatic high-grade intracranial atherosclerotic stenosis：a randomized clinical trial[J]. JAMA Neurol，2022，79（2）：176-184.
[43] SUN X，DENG Y M，ZHANG Y，et al. Balloon angioplasty vs. medical management for intracranial artery stenosis：the BASIS randomized clinical trial[J]. JAMA，2024，332（13）：1059-1069.
[44] WANG A X，JIA B X，ZHANG X L，et al. Efficacy and safety of butylphthalide in patients with acute ischemic stroke：a randomized clinical trial[J]. JAMA Neurol，2023，80（8）：851-859.
[45] FU Y，WANG A X，TANG R H，et al. Sublingual edaravone dexborneol for the treatment of acute ischemic stroke：the TASTE-SL randomized clinical trial[J]. JAMA Neurol，2024，81（4）：319-326.
[46] CHEN H S，CUI Y，LI X Q，et al. Effect of remote ischemic conditioning vs. usual care on neurologic function in patients with acute moderate ischemic stroke：the RICAMIS randomized clinical trial[J]. JAMA，2022，328（7）：627-636.
[47] HOU C B，LAN J，LIN Y N，et al. Chronic remote ischaemic conditioning in patients with symptomatic intracranial atherosclerotic stenosis（the RICA trial）：a multicentre，randomised，double-blind sham-controlled trial in China[J]. Lancet Neurol，2022，21（12）：1089-1098.
[48] GAO F，TONG X，JIA B X，et al. Bailout intracranial angioplasty or stenting following thrombectomy for acute large vessel occlusion in China（ANGEL-REBOOT）：a multicentre，open-label，blinded-endpoint，randomised controlled trial[J]. Lancet Neurol，2024，23（8）：797-806.
[49] LIU J M，ZHOU Y，ZHANG L，et al. Balloon guide catheters for endovascular thrombectomy in patients with acute ischaemic stroke due to large-vessel occlusion in China（PROTECT-MT）：a multicentre，open-label，blinded-endpoint，randomised controlled trial[J]. Lancet，2024，404（10468）：2165-2174.
[50] RESCUE BT Trial Investigators. Effect of intravenous tirofiban vs. placebo before endovascular thrombectomy on functional outcomes in large vessel occlusion stroke：the RESCUE BT randomized clinical trial[J]. JAMA，2022，328（6）：543-553.
[51] LI W L，LAN J，WEI M，et al. Normobaric hyperoxia combined with endovascular treatment for acute ischaemic stroke in China（OPENS-2 trial）：a multicentre，randomised，single-blind，sham-controlled trial[J]. Lancet，2025，405（10477）：486-497.
[52] MARVEL Trial Authors for the MARVEL Investigators. Methylprednisolone as adjunct to endovascular thrombectomy for large-vessel occlusion stroke：the MARVEL randomized clinical trial[J]. JAMA，2024，331（10）：840-849.
[53] LIU C，GUO C W，LI F L，et al. Intra-arterial urokinase after endovascular reperfusion for acute ischemic stroke：the POST-UK randomized clinical trial[J]. JAMA，2025，333（7）：589-598.
[54] HUANG J C，YANG J，LIU C，et al. Intra-arterial tenecteplase following endovascular reperfusion for large vessel occlusion acute ischemic stroke：the POST-TNK randomized clinical trial[J]. JAMA，2025，333（7）：579-588.
[55] YANG P F，SONG L L，ZHANG Y W，et al. Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke（ENCHANTED2/MT）：a multicentre，open-label，blinded-endpoint，randomised controlled trial[J]. Lancet，2022，400（10363）：1585-1596.
[56] LIANG F，WU Y X，WANG X Y，et al. General anesthesia vs. conscious sedation for endovascular treatment in patients with posterior circulation acute ischemic stroke：an exploratory randomized clinical trial[J]. JAMA Neurol，2023，80（1）：64-72.
[57] WANG Y L，LI Z X，ZHAO X Q，et al. Effect of a multifaceted quality improvement intervention on hospital personnel adherence to performance measures in patients with acute ischemic stroke in China：a randomized clinical trial[J]. JAMA，2018，320（3）：245-254.
[58] WANG C J，GU H Q，ZONG L X，et al. Effectiveness of a quality improvement intervention on reperfusion treatment for patients with acute ischemic stroke：a stepped-wedge cluster randomized clinical trial[J/OL]. JAMA Netw Open，2023，6（6）：e2316465[2025-03-02]. https://doi.org/10.1001/jamanetworkopen.2023.16465.