Intravenous thrombolysis for acute ischemic stroke, what does the 2021 ESO guide say?

*It is only for medical professionals to read and refer to what kind of advice the guide based on a large number of evidence-based evidence gives, let's learn and understand together! The 2021 version of the "European Stroke Organization (ESO) Acute Ischemic Stroke Intravenous Thrombolysis Guidelines" (hereinafter referred to as the "Guide") was released on February 19, 2021 in EUROPEAN STROKE JOURNAL.
In order to provide a certain reference for Chinese physicians, the "Medical Community Neurology Channel" has made a preliminary compilation of the recommendations of the guidelines.

The guidelines divide the use of intravenous thrombolytic drugs for acute ischemic stroke into 14 categories to elaborate, provide 48 recommendations, cover various common clinical situations, and attach the quality of evidence (high, medium, low, very low) and The strength of the recommendation (strong, weak, lack of relevant evidence), and there is no evidence-based recommendation.
The expert group intimately gave a consensus as a reference.
Next, let us learn together! 1.
Treatment within 4.
5 hours after onset 1.
Alteplase thrombolytic therapy is recommended for acute ischemic stroke within 4.
5 hours of onset (strong recommendation, high-quality evidence).

2.
Treat between 4.
5-9 hours after the onset, without advanced imaging (only CT plain scan) 2.
For patients with acute ischemic stroke lasting 4.
5-9 hours (known onset time), and plain scan There is no advanced brain imaging other than CT, and intravenous thrombolysis is not recommended (strong recommendation, moderate quality evidence).

3.
Treatment between 4.
5-9 hours after the onset, with advanced imaging 3.
For ischemic stroke patients whose duration is 4.
5-9 hours (the time of onset is clear) and CT or MRI core/perfusion does not match*, and not suitable Or for patients who do not plan to mechanically remove the thrombus, intravenous thrombolysis with alteplase is recommended (strong recommendation, low-quality evidence). *: Use automated processing software to evaluate core/perfusion mismatch, defined as follows: infarct core volume <70ml; severely low perfusion volume/infarct core volume>1.
2; mismatch volume>10ml; rCBF<30%( CT perfusion) or ADC<620m2/s (diffusion MRI); Tmax>6s (perfusion CT or perfusion MRI).

Expert consensus: For ischemic stroke patients with a duration of 4.
5-9 hours (with clear onset time) and no CT or MRI core/perfusion mismatch, all 9 experts recommend no thrombolysis.

For patients with ischemic stroke whose duration is 4.
5-9 hours (the time of onset is clear) and CT or MRI core/perfusion does not match, if they go directly to the embolization center and meet the indications for mechanical embolization, the expert group cannot perform mechanical embolization.
A consensus was reached on whether intravenous thrombolysis should be performed before embolization.

For patients with ischemic stroke with a duration of 4.
5-9 hours (time of onset is clear) and CT or MRI core/perfusion mismatch, if they visit a non-thrombectomy center and meet the indications for mechanical thrombectomy, 6 out of 9 experts Name recommends intravenous thrombolysis before mechanical thrombus removal.

4.
Stroke after waking up/unknown time of onset 4.
For patients with stroke after waking up, if the last seen normal time is more than 4.
5 hours, MRI DWI-FLAIR does not match, and it is not suitable or planned for mechanical thrombus removal, it is recommended to use A Teplase intravenous thrombolysis (strong recommendation, high-quality evidence).

5.
For patients with acute ischemic stroke who have a stroke after waking up, if CT or MRI core/perfusion mismatch* (*same as before) within 9 hours from the midpoint of sleep, and mechanical thrombus removal is not suitable or planned, it is recommended Intravenous thrombolysis with alteplase (strong recommendation, moderate quality evidence).

Expert consensus: For patients with acute ischemic stroke who go directly to the thrombectomy center after waking up, if there are indications to receive both intravenous thrombolysis and mechanical thrombectomy, 6 of the 9 experts recommend intravenous thrombolysis before mechanical thrombectomy bolt.

For patients with acute ischemic stroke who have a stroke after waking up to a non-thrombectomy center, if there are indications to receive both intravenous thrombolysis and mechanical thrombolysis, 7 out of 9 experts recommend intravenous thrombolysis before mechanical thrombectomy.

5.
Tenecteplase 6.
For patients whose onset time is less than 4.
5h and are not eligible for thrombectomy, we recommend using alteplase instead of tenecteplase for intravenous thrombolysis (weak recommendation, low-quality evidence).

7.
For patients whose onset time is less than 4.
5h with large vessel occlusion and are eligible for thrombus removal, consider intravenous thrombolysis before thrombus removal.
We recommend using 0.
25mg/kg tenecteplase instead of 0.
9mg/kg Alteplase (weak recommendation, low-quality evidence).

6.
Low-dose alteplase 8.
For patients with acute ischemic stroke whose onset time is less than 4.
5 hours, we recommend that standard-dose alteplase (0.
9 mg/kg) is better than low-dose alteplase (strong Recommendation, high-quality evidence).

7.
Adjuvant therapy 9.
For patients with acute ischemic stroke whose onset time is less than 4.
5 hours, it is recommended not to use antithrombotic drugs within 24 hours of intravenous thrombolysis, and not to use antithrombotic drugs as an aid to intravenous thrombolysis with alteplase Treatment (strong recommendation, low-quality evidence).

10.
For patients with acute ischemic stroke whose onset time is less than 4.
5 hours, it is recommended not to perform ultrasound-enhanced thrombolysis in patients receiving intravenous thrombolysis (strong recommendation, low-quality evidence).

8.
Advanced age, multiple illnesses, frailty or previous disability 11.
For patients with acute ischemic stroke with an onset time of <4.
5 hours and age> 80 years old, intravenous thrombolysis with alteplase is recommended (strong recommendation, high-quality evidence).

12.
For patients with acute ischemic stroke with onset time <4.
5h, multiple diseases, weakness or previous disability, intravenous thrombolysis with alteplase is recommended (weak recommendation, very low-quality evidence).

Expert consensus: 9 experts jointly recommended that age itself should not be a limiting factor for intravenous thrombolysis, even in other situations covered by this guide, such as stroke after waking; ischemic stroke lasting 4.
5-9 hours ( Time of onset is clear), CT or MRI core/perfusion mismatch; mild stroke with disabling symptoms, etc.

9.
Light stroke and stroke with rapid improvement of neurological symptoms 13.
For patients with acute mild disabling ischemic stroke whose onset time is less than 4.
5h, we recommend intravenous thrombolysis with alteplase (strong recommendation, moderate quality evidence) . 14.
In patients with acute mild non-disabling ischemic stroke with onset time <4.
5h, intravenous thrombolysis is not recommended (weak recommendation, moderate quality evidence).

15.
Patients with acute mild non-disabling ischemic stroke whose onset time is less than 4.
5h, and the existence of large vessel occlusion has been confirmed, and there is insufficient evidence to make evidence-based recommendations (insufficient evidence).

Expert consensus: For patients with acute mild non-disabling ischemic stroke and large vessel occlusion with an onset time of <4.
5 hours, 6 out of 8 experts recommend intravenous thrombolysis with alteplase.

16.
There is insufficient evidence to make recommendations for patients with acute ischemic stroke whose onset time is less than 4.
5h and whose neurological symptoms improve rapidly.

Please see the expert consensus statement below (insufficient evidence).

Expert consensus: In patients with acute ischemic stroke whose onset time is less than 4.
5h, if the neurological symptoms improve rapidly, but there is still the possibility of disability, 8 out of 9 experts recommend intravenous thrombolysis with alteplase.

The expert group agreed that treatment decisions should be based on the clinical manifestations at the time of treatment and cannot wait for the relief of symptoms.

10.
Severe stroke 17.
In patients with severe acute ischemic stroke whose onset time is less than 4.
5h, we recommend intravenous thrombolysis with alteplase (strong recommendation, moderate quality evidence).

18.
For acute ischemic stroke with an onset time of <4.
5h, and severe stroke patients defined by the degree of early ischemic changes on CT, we recommend that intravenous thrombolysis with alteplase be considered in specific cases (see experts below Consensus statement) (weak recommendation, very low-quality evidence).

Expert consensus: For patients with severe stroke with large imaging infarction (for example, early ischemic changes exceeding 1/3 of the middle cerebral artery drainage area or ASPECTS<7 on plain CT), 7 of 9 experts recommend to those who meet certain conditions The patient underwent intravenous thrombolysis with alteplase.

Patient selection criteria may include: indications for alternative reperfusion therapy (mechanical thrombectomy), results of advanced imaging (especially core/perfusion mismatch), duration of symptoms, scope of white matter lesions, and other contraindications for intravenous thrombolysis Certificate and past disability.

11.
Hypertension and hyperglycemia ▌ Hypertension on admission 19.
Patients with acute ischemic stroke whose onset time is less than 4.
5h, if the systolic blood pressure continues to be >185mmHg or the diastolic blood pressure is >110mmHg (even after antihypertensive treatment), We do not recommend intravenous thrombolysis (strong recommendation, very low-quality evidence).

20.
For patients with acute ischemic stroke whose onset time is less than 4.
5h, and for patients whose blood pressure exceeds 185/110mmHg (and subsequently drops below 185/110mmHg), we recommend intravenous thrombolysis with alteplase (strong recommendation, low-quality evidence) .

▌ Pre-stroke hypertension 21.
Patients with acute ischemic stroke with an onset time of less than 4.
5 hours and a known history of pre-stroke hypertension are recommended for intravenous thrombolysis with alteplase (strong recommendation, moderate quality evidence).

▌ High blood glucose at admission 22.
Patients with acute ischemic stroke with onset time <4.
5h, blood glucose >22.
2mmol/L (400mg/Dl), suggest alteplase thrombolytic therapy (weak recommendation, very low-quality evidence).

Intravenous thrombolysis should not prevent patients with acute ischemic stroke with hyperglycemia from receiving insulin therapy.

▌ Diabetes 23.
Patients with acute ischemic stroke with a known history of diabetes with an onset time of <4.
5h are advised to use alteplase for intravenous thrombolysis (strong recommendation, moderate quality evidence).

12.
Application of antithrombotic drugs before stroke▌ Antiplatelet drugs before stroke 24.
Patients with acute ischemic stroke whose onset time is less than 4.
5h, if single or dual antiplatelet drugs are used before stroke, alteplase is recommended Intravenous thrombolysis (strong recommendation, low-quality evidence).

▌ Use vitamin K antagonist before stroke 25.
Patients with acute ischemic stroke whose onset time is less than 4.
5h, who have used vitamin K antagonist and the international normalized ratio (INR) ≤1.
7, suggest intravenous thrombolysis with alteplase (strong recommendation) , Low-quality evidence).

26.
Patients with acute ischemic stroke whose onset time is less than 4.
5h have used vitamin K antagonists and have an INR> 1.
7.
Thrombolysis is not recommended (strong recommendation, very low-quality evidence). 27.
Patients with acute ischemic stroke whose onset time is less than 4.
5h have used vitamin K antagonists and the coagulation test results are unknown, so thrombolysis is not recommended (strong recommendation, very low-quality evidence).

▌ Use new oral anticoagulants (NOACs) before stroke 28.
Patients with acute ischemic stroke whose onset time is less than 4.
5h, if NOACs are used within 48 hours before the onset of the stroke, and there is no specific coagulation test available (ie xa The anti-Xa activity of factor inhibitors, the thrombin time of dabigatran, or the blood concentration of NOACs), no thrombolysis is recommended (strong recommendation, very low-quality evidence).

29.
For patients with acute ischemic stroke whose onset time is less than 4.
5h, if NOACs are used within 48 hours before the onset of the stroke, and the anti-Xa activity is less than 0.
5U/ml (factor Xa inhibitor) or thrombin time is less than 60s (direct For patients with thrombin inhibitors, there is insufficient evidence to make evidence-based recommendations (the relevant evidence is insufficient, see the expert consensus below).

30.
In patients with acute ischemic stroke whose onset time is less than 4.
5h, if dabigatran is used within 48 hours before the onset of the stroke, there is insufficient evidence to recommend or oppose the use of edacizumab (dabigatran) Specific reversal agent) and alteplase intravenous thrombolysis combined therapy, rather than thrombolysis (the relevant evidence is insufficient, see expert consensus below).

Expert consensus: In patients with acute ischemic stroke whose onset time is less than 4.
5h, if NOACs are used within 48 hours of the onset of the stroke, and the anti-Xa activity is less than 0.
5U/ml (factor Xa inhibitor) or thrombin time is less than 60s (direct clotting) In patients with enzyme inhibitors, 7 out of 9 experts recommend intravenous thrombolysis with alteplase.

For patients with acute ischemic stroke whose onset time is less than 4.
5h, if dabigatran is used within 48 hours before the onset of the stroke, 8 of the 9 experts recommend the combined use of idacelizumab and alteplase Intravenous thrombolysis, rather than no thrombolysis.

For patients with acute ischemic stroke whose onset time is less than 4.
5h, factor Xa inhibitors should be used within 48 hours before the onset of the stroke.
All experts recommend against thrombolysis instead of combined use of Andexanet (andexanet, specific for factor Xa inhibitors).
Sex reversal drugs) and alteplase intravenous thrombolysis. 13.
Potential risk factors for bleeding▌ Low platelet count 31.
Patients with acute ischemic stroke whose onset time is less than 4.
5h, if the platelet count is less than 100*109/L, thrombolysis is not recommended (weak recommendation, very low quality evidence).

32.
In patients with acute ischemic stroke whose onset time is less than 4.
5h, the platelet count is unknown before the start of intravenous thrombolysis, and there is no reason to expect abnormal values.
It is recommended to start alteplase intravenous thrombolysis while waiting for the laboratory test results ( Strong recommendation, very low-quality evidence).

▌ Recent trauma or surgery 33.
Patients with acute ischemic stroke whose onset time is less than 4.
5 hours, if they have undergone major surgery on non-compressible parts (such as the abdomen, chest, intracranial, well-vascularized tissue or large arteries) within 14 days, and subsequent internal bleeding May cause severe bleeding, and thrombolysis is not recommended (strong recommendation, very low-quality evidence).

▌ History of intracranial hemorrhage 34.
Patients with acute ischemic stroke whose onset time is less than 4.
5h have a history of intracranial hemorrhage, and there is insufficient evidence to make evidence-based recommendations (the relevant evidence is insufficient, see the expert consensus below).

Expert consensus: In patients with acute ischemic stroke whose onset time is less than 4.
5h, with a history of intracranial hemorrhage, 8 out of 9 experts recommend intravenous thrombolysis with alteplase in specific cases.

For example, the bleeding has passed for a long time, or the bleeding is non-recurrent (such as trauma) or the root cause of the bleeding has been removed (such as subarachnoid hemorrhage through endovascular aneurysm embolization or surgical aneurysm clipping, or caused Specific antithrombotic drugs for bleeding have been discontinued), then intravenous thrombolysis can be considered.

▌ Cerebral microhemorrhage 35.
Patients with acute ischemic stroke whose onset time is less than 4.
5h have cerebral microhemorrhage.
If the burden of cerebral microhemorrhage is unknown or has low knowledge (for example, <10), intravenous alteplase is recommended Shuan (weak recommendation, low-quality evidence).

36.
Patients with acute ischemic stroke whose onset time is less than 4.
5h have cerebral microhemorrhage.
If the burden of cerebral microhemorrhage is known to be high (for example, >10), thrombolysis is not recommended (weak recommendation, low-quality evidence).

Expert consensus: For duration <4.

▌ White matter lesions 37.
In patients with acute ischemic stroke whose onset time is less than 4.
5h, if there are mild to moderate white matter lesions, intravenous thrombolysis with alteplase is recommended (strong recommendation, moderate quality evidence).

38.
In patients with acute ischemic stroke whose onset time is less than 4.
5h, if there are severe white matter lesions, intravenous thrombolysis with alteplase is recommended (weak recommendation, low-quality evidence).

▌ Cerebral aneurysm 39.
For patients with acute ischemic stroke with a duration of less than 4.
5 hours, if there is an unruptured cerebral aneurysm, intravenous thrombolysis with alteplase is recommended (weak recommendation, very low-quality evidence).

14.
Other comorbid diseases▌ History of ischemic stroke 40.
For patients with acute ischemic stroke with a duration of less than 4.
5 hours, and patients with a history of ischemic stroke in the past three months, there is insufficient evidence-based evidence For recommendations, please refer to the expert consensus (insufficient evidence).

Expert consensus: Patients with acute ischemic stroke whose onset time is less than 4.
5h have a history of ischemic stroke in the past three months.
All 9 experts recommend the use of alteplase for intravenous thrombolysis in patients who meet certain conditions , Such as in the case of small infarction, stroke occurring more than one month or good clinical recovery.

▌ Epilepsy 41.
Patients with acute ischemic stroke whose onset time is less than 4.
5 hours, are accompanied by seizures at the time of onset, and are not suspected of stroke mimics, and have not found serious head trauma.
Alteplase intravenous thrombolysis is recommended (weak recommendation, Very low-quality evidence).

▌ Dissection 42.
For patients with acute ischemic stroke and aortic arch dissection with an onset time of <4.
5h, it is recommended not to dissolve thrombolysis (strong recommendation, very low-quality evidence).

43.
For patients with acute ischemic stroke and solitary carotid artery dissection with an onset time of <4.
5h, intravenous thrombolysis with alteplase is recommended (weak recommendation, low-quality evidence).

44.
There is insufficient evidence to make recommendations for patients with acute ischemic stroke and intracranial artery dissection with an onset time of <4.
5h.

Please refer to the following expert consensus (insufficient evidence).

Expert consensus: For patients with acute ischemic stroke and intracranial artery dissection with an onset duration of <4.
5h, 6 out of 9 experts recommend no thrombolysis. ▌ Myocardial infarction 45.
For patients with acute ischemic stroke whose onset time is less than 4.
5h, if there is a subacute (> 6 hours) ST-segment elevation myocardial infarction in the last 7 days, thrombolysis is recommended (weak recommendation, very low quality evidence).

46.
​​For patients with acute ischemic stroke whose onset time is less than 4.
5h, if there is a non-ST-segment elevation myocardial infarction within the last 3 months, intravenous thrombolysis with alteplase is recommended (weak recommendation, very low-quality evidence).

47.
For patients with acute ischemic stroke whose onset time is less than 4.
5h, if there is an ST-segment elevation myocardial infarction in the last 1 week to 3 months, there is insufficient evidence to make recommendations.

Please refer to the following expert consensus (insufficient evidence).

Expert consensus: All team members recommend the use of alteplase under specific circumstances.

The variables to consider are the size of the myocardial infarction, whether to recanalize the myocardial infarction, and the echocardiographic results.

▌ Infective endocarditis 48.
For patients with acute ischemic stroke whose onset time is less than 4.
5h, if infective endocarditis is diagnosed or suspected, thrombolysis is recommended (strong recommendation, weak quality evidence).

References: [1] Berge E, Whiteley W, Audebert H, et al.
European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke.
European Stroke Journal.
February 2021.
doi:10.
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