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Guideline
Chinese Stroke Association guidelines for clinical management of ischaemic cerebrovascular diseases: executive summary and 2023 update
  1. Liping Liu1,2,
  2. Zixiao Li1,2,3,4,5,
  3. Hongyu Zhou1,2,
  4. Wanying Duan1,2,
  5. Xiaochuan Huo6,
  6. Weihai Xu7,
  7. Shujuan Li8,
  8. Ximing Nie1,2,
  9. Huihui Liu1,2,9,
  10. Jinjie Liu10,
  11. Dapeng Sun2,11,
  12. Yufei Wei1,2,
  13. Guitao Zhang8,
  14. Weizhuang Yuan7,
  15. Lina Zheng1,2,
  16. Jingyi Liu1,2,
  17. David Wang12,
  18. Zhongrong Miao2,11,
  19. Yongjun Wang1,2,3,13
  1. 1 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
  2. 2 China National Clinical Research Center for Neurological Diseases, Beijing, China
  3. 3 National Center for Healthcare Quality Management in Neurological Diseases, Beijing, China
  4. 4 Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, China
  5. 5 Chinese Institute for Brain Research, Beijing, China
  6. 6 Neurological Disease Center, Cerebral Vascular Disease Department, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
  7. 7 Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  8. 8 Department of Neurology, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  9. 9 Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, Suzhou, China
  10. 10 Department of General Medicine, Dalian Municipal Central Hospital Affiliated Dalian University of Technology, Dalian, China
  11. 11 Interventional Neuroradiology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
  12. 12 Neurovascular Division, Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA
  13. 13 Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
  1. Correspondence to Yongjun Wang; yongjunwang{at}ncrcnd.org.cn

Abstract

Background China is one of the countries with the highest burden of stroke. Implementing multidimensional management guidelines will help clinicians practise evidence-based care, improve patient outcomes and alleviate societal burdens. This update of the 2019 edition will provide the latest comprehensive recommendations for the diagnosis and treatment of ischaemic cerebrovascular diseases.

Methods We conducted a comprehensive search on MEDLINE (via PubMed) up to 31 August 2023. The writing team established the recommendations through multiple rounds of online and offline discussions. Each recommendation was graded using the evidence grading algorithm developed by the Chinese Stroke Association (CSA). The draft was reviewed and finalised by the CSA Stroke Guidelines Writing Committee.

Results This update included revisions of 15 existing recommendations and 136 new recommendations in the following areas of stroke care: emergency assessment and diagnosis of ischaemic cerebrovascular disease, acute-phase reperfusion therapy, evaluation of underlying mechanisms, antithrombotic therapy, prevention and treatment of complications, and risk factor management.

Conclusions This guideline updated the recommendations for the clinical management of ischaemic cerebrovascular disease from 2019.

  • Ischaemic Cerebrovascular Diseases
  • Guidelines
  • Management
  • Diagnosis
https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/svn-2023-002998

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    Highlights

    The clinical management of ischaemic cerebrovascular diseases comprises a total of 287 recommendations, including 136 new recommendations and 15 revised recommendations from the version in 2019. These highlights reflect significant new therapeutic options developed in recent times that will impact the daily management of patients with acute ischaemic stroke (AIS).

    Reperfusion therapy

    1. Tenecteplase (TNK) 0.25 mg/kg intravenous push has been proven non-inferior to intravenous standard dosage of recombinant tissue plasminogen activator (rt-PA) to treat patients with AIS with <4.5 hours of onset (Section 3.1).

    2. For patients with anterior circulation large vessel occlusion (LVO) type of AIS who present within 4.5 hours of symptom onset, the efficacy of intravenous TNK (0.25 mg/kg) is non-inferior to intravenous rt-PA (0.9 mg/kg) before intra-arterial (IA) mechanical thrombectomy (MT). The TNK might offer better reperfusion outcomes, while the incidence of symptomatic intracerebral haemorrhage (sICH) remains similar (Section 3.1).

    3. For patients with AIS with anterior circulation LVO and a large core infarct within 24 hours of onset and who meet the inclusion criteria of the RESCUE-Japan LIMIT, ANGEL-ASPECT and SELECT 2 trials, IA MT is recommended (Section 3.2).

    4. For patients with acute basilar artery occlusion (BAO) within 6 hours of onset who meet the inclusion criteria of the ATTENTION trial, IA MT is recommended (Section 3.2).

    5. Patients with acute BAO within 6–12 hours of onset are recommended for IA MT when they meet the inclusion criteria of the ATTENTION or BAOCHE trials (Section 3.2).

    6. Patients with acute BAO within 12–24 hours of onset are recommended for MT when they meet the inclusion criteria of the BAOCHE trial (Section 3.2).

    Antiplatelet therapy

    1. Intravenous tirofiban can be beneficial in those patients who meet the RESCUE BT2 trial inclusion criteria (Section 4.1).

    2. For patients with non-cardioembolic minor ischaemic stroke (IS) (National Institutes of Health Stroke Scale (NIHSS) score ≤3) or high-risk transient ischaemic attack (TIA) (ABCD2 score ≤4) who present within 24 hours of symptom onset, if CYP2C19 gene testing can be tested and the patient carries CYP2C19 loss-of-function (LoF) alleles, ticagrelor plus aspirin for 21 days (ticagrelor loading dose of 180 mg on the first day, followed by 90 mg two times per day) and continue with ticagrelor monotherapy (90 mg two times per day) for 90 days are recommended (Section 4.2).

    3. For patients with moderate IS (NIHSS score of 4–5) who present within 24 hours of symptom onset, ticagrelor plus aspirin for 30 days (ticagrelor loading dose of 180 mg on the first day, followed by 90 mg two times per day) may reduce the risk of recurrent stroke and death within 30 days (Section 4.2).

    Brain cytoprotection

    1. Brain cytoprotection with edaravone dexborneol (intravenous 37.5 mg/dose, once every 12 hours, for 14 days) may improve clinical outcomes in patients with AIS (Section 5.1).

    2. DL-3-n-butylphthalide (NBP), 25 mg, dissolved in 100 mL sodium chloride and given as intravenous injection two times per day for the first 14 days, followed by soft 0.2 g capsules of NBP three times a day for the next 76 days, may serve as an adjunct treatment to reperfusion therapy and have the potential to improve functional outcomes in patients with AIS (Section 5.1).

    Risk factor management

    1. For patients who cannot tolerate statins or have contraindications to statin therapy, the use of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors or ezetimibe may be considered (Section 9.2).

    2. For patients with IS or TIA with fasting triglycerides (TG) ≥135 mg/dL (1.52 mmol/L), who have received moderate or high-intensity statin therapy, a glycated haemoglobin (HbA1c) level <10%, and no history of pancreatitis, atrial fibrillation, or severe heart failure, treatment with icosapent ethyl (2 g two times per day) can reduce the risk of stroke recurrence (Section 9.2).

    Introduction

    The incidence of stroke in the Chinese population continues to rise, accounting for nearly one-fourth of the global annual stroke cases.1 Among adults aged 40 years or above in China, IS accounted for approximately 86.8% of all strokes.2 Timely updates to the guidelines can provide new evidence-based recommendations for diagnosis, acute-phase treatment, prevention and management of complications, and secondary prevention for IS.3

    Since the publication of the 2019 Chinese Stroke Association (CSA) guidelines, notable advancements have emerged in acute-phase reperfusion therapy and antiplatelet treatments for secondary IS prevention. The findings of several high-quality randomised controlled trials (RCTs) conducted in China will have an impact on stroke care.4–6 Some new lipid-lowering agents are also helpful in stroke prevention.

    We conducted a comprehensive search of MEDLINE (via PubMed) up to 31 August 2023, and compiled the relevant information into a tabular format. The writing team established the level of recommendation through multiple rounds of online and offline discussions. Each recommendation was graded using the evidence grading algorithm developed by the CSA (table 1). The updated guideline kept the nine sections: definitions, emergency assessment and diagnosis, reperfusion therapy, antiplatelet therapy, other treatments in the acute phase, general supportive treatment and management of complications, early evaluation of the aetiology and pathogenesis, interventions targeting aetiology and pathogenesis, risk factor management and long-term intervention.

    View this table:
    Table 1

    The recommended classification and levels of evidence developed by the Chinese Stroke Association

    Section 1: definitions associated with ischaemic cerebrovascular diseases

    The definitions associated with ischaemic cerebrovascular diseases are shown in table 2.

    View this table:
    Table 2

    Relative definitions of ischaemic cerebrovascular disease

    Section 2: emergency assessment and diagnosis of patients with AIS

    The acute care process for patients with AIS is shown in figure 1. The emergency diagnostic and examination process flow chart for patients with AIS is shown in figure 2.

    View this table:
    Figure 1
    Figure 1

    The acute care process for patients with acute ischaemic stroke. BP, blood pressure; CTA, CT angiography; CXR, chest X-ray; DBP, diastolic BP; IA, intra-arterial; INR, international normalised ratio; IV, intravenous; LVO, large vessel occlusion; MT, mechanical thrombectomy; NIHSS, National Institutes of Health Stroke Scale; SBP, systolic BP; SCR, serum creatinine; TIA, transient ischaemic attack.

    Figure 2
    Figure 2

    The emergency diagnostic and examination process flow chart for patients with acute ischaemic stroke (AIS). CTA, CT angiography; MRA, magnetic resonance angiography; US, ultrasonography.

    Section 3: reperfusion therapy for AIS

    The management process of intravenous thrombolysis for patients with AIS within 4.5 hours of symptom onset is shown in figure 3. The management process of intravenous thrombolysis for patients with AIS with an onset between 4.5 and 9 hours or wake-up stroke is shown in figure 4. The flow chart for IA MT in patients with AIS is shown in figure 5.

    Figure 3
    Figure 3

    The management process of intravenous (IV) thrombolysis for patients with acute ischaemic stroke (AIS) within 4.5 hours of symptom onset. CTA, CT angiography; IA, intra-arterial; LVO, large vessel occlusion; MT, mechanical thrombectomy.

    Figure 4
    Figure 4

    The management process of intravenous (IV) thrombolysis for patients with acute ischaemic stroke (AIS) with an onset between 4.5 and 9 hours or wake-up stroke. DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery; IA, intra-arterial; LVO, large vessel occlusion; MT, mechanical thrombectomy; rt-PA, recombinant tissue plasminogen activator.

    Figure 5
    Figure 5

    The intra-arterial (IA) mechanical thrombectomy (MT) for patients with acute ischaemic stroke. ASPECTS, Alberta Stroke Program Early CT Score; BAO, basilar artery occlusion; DA, direct aspiration; IAT, intra-arterial thrombolysis; IV, intravenous; LVO, large vessel occlusion; mRS, modified Rankin Scale; NICU, neurological intensive care unit; NIHSS, National Institutes of Health Stroke Scale.

    Section 3.1 Intravenous thrombolysis

    View this table:

    Section 3.2 Bridging/MT

    View this table:

    Section 4: antiplatelet therapy for acute ischaemic cerebrovascular disease

    The antiplatelet treatment process for patients with AIS is shown in figure 6.

    Figure 6
    Figure 6

    The antiplatelet treatment process for patients with acute ischaemic stroke (AIS). bid, two times per day; NIHSS, National Institutes of Health Stroke Scale; TIA, transient ischaemic attack.

    Section 4.1 Single antiplatelet therapy

    View this table:

    Section 4.2 Dual antiplatelet therapy

    View this table:

    Section 4.3 Triple antiplatelet therapy

    View this table:

    Section 5: other treatments in the acute phase

    Section 5.1 Brain cytoprotection

    View this table:

    Section 5.2 Brain cytoprotection

    View this table:

    Section 5.3 Hyperbaric oxygen therapy

    View this table:

    Section 6: general supportive treatment and management of complications

    The management process for brain oedema/intracranial hypertension is shown in figure 7. The management process for haemorrhagic transformation in patients with AIS is shown in figure 8. The management process for the first seizure within 24 hours of stroke onset is shown in figure 9.

    View this table:
    Figure 7
    Figure 7

    The management process for brain oedema/intracranial hypertension. BP, blood pressure; NICU, neurological intensive care unit.

    Figure 8
    Figure 8

    The management process for haemorrhagic transformation in patients with acute ischaemic stroke. INR, international normalised ratio.

    Figure 9
    Figure 9

    The management process for the first seizure within 24 hours of stroke onset.

    Section 7: early evaluation of aetiology and pathogenesis of ischaemic cerebrovascular disease

    The diagnostic process for cryptogenic stroke is shown in figure 10.

    View this table:
    View this table:
    Figure 10
    Figure 10

    The diagnostic process for cryptogenic stroke. CSF, cerebrospinal fluid; CTA, CT angiography; DSA, digital subtraction angiography; MRA, magnetic resonance angiography; TCD, transcranial Doppler; TEE, transoesophageal echocardiography; TIA, transient ischaemic attack; TTE, transthoracic echocardiography.

    Section 8: interventions targeting aetiology and pathogenesis

    The treatment strategy for valvular heart disease is shown in figure 11.

    View this table:
    View this table:
    View this table:
    View this table:
    View this table:
    Figure 11
    Figure 11

    The treatment strategy of valvular heart disease. TIA, transient ischaemic attack.

    Section 9: risk factor management and long-term intervention

    The flow chart for blood pressure management within 72 hours after the onset of AIS is shown in figure 12. The flow chart for lipid-lowering management in patients with AIS is shown in figure 13. The flow chart for blood glucose management in patients with AIS is shown in figure 14.

    Figure 12
    Figure 12

    The blood pressure (BP) management within 72 hours after the onset of acute ischaemic stroke (AIS). IA, intra-arterial; IV, intravenous; MT, mechanical thrombectomy; rt-PA, recombinant tissue plasminogen activator.

    Figure 13
    Figure 13

    The lipid-lowering management in patients with acute ischaemic stroke. *Very high risk includes a history of multiple major ASCVD events or one major ASCVD event and multiple high-risk conditions. Major ASCVD events: history of ischaemic stroke; recent acute coronary syndrome (within the past 12 months); history of myocardial infarction (other than recent acute coronary syndrome event listed above); symptomatic peripheral arterial disease (history of claudication with ankle-brachial index <0.85 or previous revascularisation or amputation). High-risk conditions: age ≥65 years; heterozygous familial hypercholesterolaemia; history of coronary artery bypass surgery or percutaneous coronary intervention outside of the major ASCVD events; diabetes; hypertension; chronic kidney disease (estimated glomerular filtration rate, 15–59 mL/min/1.73 m2); current smoking. ASCVD, atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol; PCSK9, proprotein convertase subtilisin/kexin 9.

    Figure 14
    Figure 14

    The flow chart for blood glucose management in patients with acute ischaemic stroke. GLP-1, glucagon-like peptide-1; HbA1c, glycated haemoglobin; OGTT, oral glucose tolerance test; SGLT2, sodium-glucose cotransporter 2.

    9.1 Blood pressure management

    View this table:

    9.2 Management of abnormal lipid metabolism

    View this table:

    9.3 Management of abnormal glucose metabolism

    View this table:

    9.4 Management of other risk factors

    View this table:

    Ethics statements

    Patient consent for publication

    Ethics approval

    Not applicable.

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    Footnotes

    • LL, ZL and HZ contributed equally.

    • Collaborators Stroke Council Writing Committee for Chinese Stroke Association Guideline (Sorted in A-Z order): Dapeng Sun, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Gaifen Liu, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Guitao Zhang, Department of Neurology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Hongyu Zhou, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Huihui Liu, Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, Suzhou, China; Jiahui Zhao, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Jiaping Chen, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Jing Jing, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Jingfan Yao, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Jingyi Liu, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Jinjie Liu, Department of General Medicine, Dalian Municipal Central Hospital Affiliated Dalian University of Technology, Dalian, China; Lina Zheng, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Liping Liu, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Man Li, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Qian Jia, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Qixuan Lu, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Ruixue Zhao, Department of Neurology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Shuang Cao, Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Shujuan Li, Department of Neurology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Tianhang Liu, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Tun zhao, Department of Neurology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Wanying Duan, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Weihai Xu, Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Weizhuang Yuan, Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Xiaochuan Huo, Neurological Disease Center, Cerebral Vascular Disease Department, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; Ximing Nie, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Xinxuan Yang, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Xiran Liu, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Xiwa Hao, Department of Neurology, Baotou Center Hospital, Baotou, China; Xu Jie, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Xuewei Xie, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Yajun Ma, Department of Neurology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Yongjun Wang, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Yufei Wei, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Zhongrong Miao, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Zixiao Li, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

    • Contributors YW, LL and ZL designed the protocol and framework and participated in revision. HZ organized and summarized the manuscript. XN and JL1 drafted the sections of emergency assessment and diagnosis. ZM, XH, DS, XN and JL1 drafted the sections of reperfusion therapy. ZL, HL and HZ drafted the sections of antiplatelet therapy, risk factor management and long-term intervention. LL, WD and YW drafted the sections of other treatments in the acute phase, general supportive treatment and management of complications. SL and GZ drafted the sections of early evaluation of the aetiology and pathogenesis. WX and WY drafted the sections of early evaluation of the aetiology and pathogenesis, interventions targeting aetiology and pathogenesis. LZ and JL2 proofread the manuscript. DW reviewed the manuscript. YW, LL, ZL, WX, and SL reviewed all the studies’ designs and interpretations and confirmed the level of evidence and classification. 1 Jinjie Liu, 2 Jingyi Liu

    • Funding This research received specific funding from the Chinese Stroke Association.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; internally peer reviewed.