Guidelines for the early diagnosis and treatment of transient ischemic attacks in China . publish

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Stroke Prevention and Control Engineering Committee

2022-2024 is the year of quality management of stroke prevention and control projects, in order to promote the standardization of stroke prevention and control work in stroke centers around the world, and implement the "Comprehensive Plan for Strengthening Stroke Prevention and Control Work to Reduce Millions of New Disabilities Project", the Office of the Brain Prevention and Control Commission of the National Health Commission has sorted out the "China Stroke Prevention and Control Guidance Specifications (2021 Edition)"

Guidelines for the early diagnosis and treatment of transient ischemic attacks in China

A transient ischemic attack (TIA) is a transient neurologic deficit

1.

【Guidelines】

Essentially, TIA and cerebral infarction are different stages

【Evidence】

1.

2.

3.

4.

2.

【Guidelines】

1.

2.

3.

(1) General examination: the evaluation includes electrocardiogram, complete blood count, coagulation function, blood electrolyte, renal function and rapid blood glucose and lipid measurement

(2) Vascular examination: CT angiography (CTA), magnetic resonance angiography (MRA), vascular ultrasound, and total cerebral angiography (DSA) can find important extracranial and extracranial vascular lesions

(3) Assessment of collateral circulation compensation and cerebral blood flow reserve: DSA, cerebral perfusion imaging, and/or transcranial color Doppler ultrasound (TCD) to assess collateral circulation compensation and cerebral blood flow reserve are necessary

(4) Examination of vulnerable plaques: fragile plaques are an important source of

(5) Cardiac evaluation: if cardioembolism is suspected, or if cervical and cerebrovascular examination and hematological screening under 45 years of age fail to determine the cause, transthoracic echocardiography (TTE) and/or transesophageal echocardiography (TEE) examination, it may be possible to find heart wall thrombosis, atrial septal abnormalities (atrioventricular wall tumors, Multiple embolitanal sources
such as ovoid closure, atrial septal defect), mitral valve vegetation, and atherosclerosis of the aortic arch.

(6) Do other relevant tests based on medical history

【Evidence】

1.
The ABCD2 score, published in 2007, is used to predict the risk
of stroke within 2 days of TIA.
The content of the score increases the risk factor for diabetes compared to the ABCD score
.
ABCD2 scores were derived from a cohort study of 2 893 people in four groups of people, and the results showed that patients in the high-risk group (6 to 7 points), the intermediate-risk group (4 to 5 points), and the low-risk group (0 to 3 points) had a high risk of stroke risk in the 2 days after TIA, respectively, which had a high predictive value
of stroke risk.
At present, the ABCD2 score is the most widely used score in the ABCD scoring system, and it has also been well verified
in the Chinese population.

2.
At present, with the increasing popularity of imaging technology, the role of imaging in predicting the risk of stroke after TIA has been gradually valued
.
If patients with clinical manifestations of TIA have a new cerebral infarction or intracranial and extracranial artery stenosis, the risk of stroke is significantly increased
.
Studies have questioned the value of a scoring system based solely on symptoms and history, highlighting the role of imaging in predicting stroke risk, but more research is needed to confirm
it.

3.
SOS-TIA (a Transient Ischemic Attack Clinic with Round-the-Clock Access) study was designed to investigate whether rapid assessment and treatment of patients with TIA could reduce the risk
of stroke recurrence.
The study enrolled 1 085 outpatients with suspected TIA within 24 hours of symptom onset to be rapidly evaluated and diagnosed, and patients with mild, positive, or suspected TIA were given immediate antithrombotic therapy
.
Results showed that the 90-day stroke incidence in confirmed patients with TIA was only 1.
24%, well below the 5.
96%
predicted by ABCD2.

4.
EXPRESS (Effect of Urgent Treatment of Transient Ischemic Attack and Minor Stroke on Early Recurrent Stroke) study is a before-and-after controlled study
。 The study consisted of two phases, the first phase enrolled 310 TIA patients, treatment was treated by TIA outpatient appointment, and the first physician recommended treatment; In the second stage, 281 patients with TIA were enrolled and appointments were cancelled, a TIA clinic was established, and treatment
was given immediately after the diagnosis of TIA.
Results showed that early active intervention in patients with TIA reduced the risk of stroke for 90 days by up to 80% without increasing adverse events such as bleeding, while early aggressive intensive intervention significantly reduced hospital stays, hospital costs, and 6-month disability rates
.

The results of the SOS-TIA and EXPRESS studies suggest that secondary prophylaxis in patients with TIA should be implemented
from the acute stage.
An analysis of the results of the database of TIA specialist clinics in the UK from 2010 to 2012 showed that the incidence of stroke in 90 days of TIA or mild stroke patients treated in the TIA specialist clinic was only 1.
3%.

Therefore, the establishment of the TIA clinic is an effective measure
.
National guidelines also emphasize early intervention
in patients with TIA.

3.
Treatment of transient ischemic attack

Because TIA is very similar in pathogenesis and clinical presentation to ischemic stroke, TIA and ischemic stroke are often included internationally in
the same prevention and treatment guidelines.
In order to simplify the operation process, the specific evidence-based medical evidence of the TIA treatment guidelines can be found in the "China Ischemic Stroke and Transient Ischemic Attack Secondary Prevention Guidelines 2014" and "China Acute Ischemic Stroke Diagnosis and Treatment Guidelines 2018", and the latest evidence-based medical evidence
is supplemented.

(1) Acute thrombolytic therapy

1.
TIA is an important acute condition, the early disability rate and the risk of recurrence is high, in the emergency department, the symptoms continue to ≥ 30 minutes, should be followed by acute ischemic stroke process to start the green channel assessment
.

2.
So far, TIA thrombolytic therapy still lacks evidence-based medical evidence, and it is recommended that for patients with aortic stenosis and high NIHSS scores, intravenous thrombolysis or mechanical thrombolysis is carried out with reference to the principle of aphrombolysis therapy in the acute stage of ischemic stroke
.

(2) Oral antithrombotic drug therapy

1.
Antithrombotic therapy of non-cardiac TIA

(1) For patients with non-cardiac TIA, it is recommended to give oral antiplatelet drugs instead of anticoagulant drugs to prevent stroke recurrence and other cardiovascular events
.

(2) Aspirin (50 to 325 mg/day) or clopidogrel (75 mg/day) monotherapy can be used as the preferred antiplatelet drug
.
The optimal dose for aspirin antiplatelet therapy is 75 to 150 mg/day
.
Aspirin (25 mg) + extended-release dipyridamole (200 mg) twice daily/day or silotrazole (100 mg) twice daily, both as an alternative therapy for
aspirin and clopidogrel 。 Latest Evidence: The results of a recently published study of Acute Stroke or Transient ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) suggest that patients with noncardiogenic high-risk TIA (ABCD2 score ≥4) have an incidence of 24 Tigrelor treatment given within hours is no different from aspirin's safety, but its efficacy is not superior to that of aspirin
.
Therefore, antiplatelet agents should be individualized based on patient risk factors, cost, tolerability, and other clinical characteristics
.

(3) Acute non-cardiac TIA with a high risk of recurrence of stroke (ABCD2 score ≥4) within 24 hours of onset should be treated with aspirin plus clopidogrel as early as possible for 21 days
.
Thereafter, either aspirin or clopidogrel can be used as first-line agents
for long-term secondary prevention.
Latest Evidence: The newly released Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) study further justifies this treatment regimen
。 The study showed that 90 days of treatment with aspirin in combination with clopidogrel reduced the risk of combined cardiovascular events in patients with non-cardiac high-risk TIA for 90 days, but also increased the incidence
of bleeding events.
Therefore, non-cardiogenic high-risk TIA, acute aspirin plus clopidogrel therapy is preferable
for 21 days.

(4) Patients with TIA who have symptomatic intracranial artery severe stenosis (stenosis rate of 70% to 99%) within 30 days of onset should be treated with aspirin plus clopidogrel as soon as possible for 90 days
.
Thereafter, either aspirin or clopidogrel can be used as first-line agents
for long-term secondary prevention.

(5) For patients with TIA with evidence of atherosclerotic plaque of the aorta arch, antiplatelet and statin therapy
are recommended.
There is no positive conclusion
on the therapeutic effect of oral anticoagulants with aspirin combined with clopidogrel.

(6) Patients with non-cardiac TIA do not recommend routine long-term aspirin combined with clopidogrel antiplatelet therapy
.

2.
Antithrombotic therapy of cardioembolic TIA

(1) For patients with TIA with atrial fibrillation (including paroxysmal fibrillation), oral anticoagulation with appropriate doses of warfarin is recommended to prevent recurrent thromboembolic events
.
The target dose of warfarin should be maintained at an INR of 2.
0 to 3.
0
.

(2) The new oral anticoagulant can be used as an alternative drug for warfarin, and the new oral anticoagulant includes dabigatran, rivaroxaban, apixaban and edoxaban, and the choice of which drug should consider individualized factors
.

(3) If patients with TIA with atrial fibrillation cannot receive oral anticoagulant therapy, aspirin monotherapy
is recommended.
Aspirin plus clopidogrel antiplatelet therapy
may also be an option.

(4) For patients with TIA with atrial fibrillation, the timing of anticoagulation should be selected according to the severity of ischemia and the risk of bleeding transformation, and anticoagulation therapy should be given to prevent stroke recurrence, and for patients with high bleeding risk, the initiation time
of anticoagulation should be appropriately delayed.

(5) For patients with TIA, undergo 24-hour Holter examination
as much as possible.
In patients of unknown origin, prolonged ECG monitoring is recommended to determine indications for anticoagulation
.

(6) In patients with TIA with acute myocardial infarction, imaging studies reveal thrombosis of the left ventricular wall, and oral anticoagulation with warfarin for at least 3 months is recommended (target INR value is 2.
5; range 2.
0 to 3.
0).

If there is no left ventricular wall thrombosis, but no or abnormal movement of the anterior wall is found, a 3-month oral anticoagulation of warfarin (target INR 2.
5; range 2.
0 to 3.
0)
should also be considered.

(7) For patients with TIA who have rheumatic mitral valve lesions but no atrial fibrillation and other risk factors (eg, carotid stenosis), oral anticoagulation with warfarin (target INR 2.
5; range 2.
0 to 3.
0)
is recommended.

(8) For patients with rheumatic mitral valve disease who have been treated with warfarin anticoagulation, antiplatelet therapy
should not be routinely combined after the occurrence of TIA.
However, if ischemic stroke or TIA is still present during adequate warfarin therapy, aspirin antiplatelet aggregation therapy may be added
.

(9) Antiplatelet aggregation therapy
may be considered in patients with TIA who do not have nonrheumatic mitral valve lesions or other valvular lesions (local aortic toxar calcification, mitral ring calcification, mitral valve prolapse, etc.
).

(10) For patients with TIA implanted with artificial heart valves, long-term oral anticoagulation with warfarin is
recommended.

(11) For patients with a prior history of TIA who have been implanted with an artificial heart valve, if the risk of bleeding is low, aspirin can be added on the basis of warfarin anticoagulation
.

(3) Non-drug treatment of symptomatic atherosclerotic transient ischemic attacks

1.
Stenosis of the external cranial segment of the carotid artery

(1) For patients with recent TIA complicated by ipsilateral extracranial stenosis (50% to 99%), CEA or CAS therapy
is recommended if the risk of perioperative death and stroke recurrence is expected to <6%.
The choice of CEA or CAS should be based on patient individualization<b11>.

(2) When the degree of stenosis of the external part of the carotid artery is < 50%, CEA or CAS treatment<b10> is not recommended.

(3) When patients with TIA have indications for treatment of CEA or CAS, if there is no contraindication to early retransmission, surgery
should be performed within 2 weeks.

2.
Extracranial vertebral artery stenosis

In patients with TIA with symptomatic atherosclerotic stenosis of the extracranial vertebrae, stent placement may be an adjunct to medical pharmacotherapy when medical therapy is ineffective
.

3.
Subclavian artery stenosis and skull and arm stem stenosis

(1) TIA patients with symptoms of posterior circulatory ischemia (subclavian artery hemoracy syndrome) caused by stenosis or occlusion of the subclavian artery may be stented or surgical if
the standard medical treatment is ineffective and there are no surgical contraindications.

(2) In patients with TIA caused by lesions of the common carotid artery or stem of the head and arms, the internal medicine treatment is ineffective and there are no surgical contraindications, and stenting or surgical treatment can be performed
.

4.
Intracranial artery stenosis

For patients with TIA who ≥ 70% of symptomatic intracranial atherosclerotic stenosis, vascular intervention may be chosen as an adjunctive technical means of medical therapy in the absence of standard medical therapy, but the choice of patient should be strict and prudent
.

(4) Risk factor control

1.
High blood pressure

(1) Patients with TIA who have not previously received antihypertensive therapy, if the systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥90mmHg several days after the onset of the disease, antihypertensive therapy should be initiated; The antihypertensive benefit of patients with blood pressure < 140/90 mmHg is unclear<b10>.

(2) If there is no absolute contraindication to patients with TIA who have a history of hypertension and have been receiving antihypertensive drugs for a long time, antihypertensive therapy
should be restarted a few days after the onset of the disease.

(3) For patients with TIA due to intracranial atherosclerotic stenosis (stenosis rate of 70% to 99%), it is recommended to reduce systolic blood pressure to less than 140 mmHg and diastolic blood pressure to less than
90 mmHg.
In patients with TIA due to low hemodynamic causes, the rate and magnitude of the blood pressure reduction should be weighed against the patient's tolerance and hemodynamic effects
.

(4) The selection of antihypertensive drugs and the selection of the type and dose and the target value of antihypertensive drugs should be individualized, and the three factors
of drugs, strokes and patients should be fully considered.

2.
Abnormal lipid metabolism

(1) For patients with non-cardiac TIA, whether accompanied by other evidence of atherosclerosis, long-term treatment with intensive statins is recommended to reduce the risk of
stroke and cardiovascular events.
There is evidence that secondary prevention is more effective
when LDL-C decreases ≥ 50% or LDL ≤ 70 mg/dl (1.
8 mmol/L).

(2) For patients with non-cardiac TIA with LDL-C≥100 mg/dl (2.
6 mmol/L), intensive statin therapy is recommended to reduce the risk of stroke and cardiovascular events; Intensive statin therapy is recommended in patients with TIA with LDL-C<100 mg/dl (2.
6 mmol/L), although evidence is lacking<b10>.

(3) For patients with TIA caused by atherosclerotic stenosis of the large arteries in the skull (stenosis rate of 70% to 99%), long-term treatment with high-intensity statins is recommended to reduce the risk of stroke and cardiovascular events, and the recommended target value is LDL-C≤70mg/dl (1.
8 mmol/L).

In patients with TIA due to extracranial aortic stenosis, long-term treatment with high-intensity statins is recommended to reduce stroke and cardiovascular events
.

(4) Long-term use of statins is generally safe
.
Patients with non-cardiac TIA with a history of intracerebral hemorrhage should weigh the risks and benefits of rational use
.

(5) During the treatment of statins, if the monitoring indicators continue to be abnormal and exclude other influencing factors, or the clinical manifestations corresponding to the abnormal indicators appear, the drug should be reduced or stopped for observation in time (reference: liver enzymes exceed the upper limit of 3 times the normal value, and the drug should be reduced for observation; Muscle enzymes exceed 5 times the upper limit of normal values and should be discontinued for observation); In the elderly or in patients with severe organ insufficiency, the initial dose should not be too large
.

3.
Abnormal glucose metabolism and diabetes

(1) The prevalence of abnormal glucose metabolism in patients with TIA is high, diabetes and prediabetes are independent risk factors for stroke recurrence or death in patients with ischemic stroke, and clinicians should pay more attention
to the management of blood glucose in patients with TIA.

(2) TIA patients should undergo fasting blood glucose and glycosylated hemoglobin monitoring after the onset of illness, and patients without a clear history of diabetes should routinely undergo oral glucose tolerance tests after the acute phase to screen for glucose metabolism abnormalities and diabetes
.

(3) Lifestyle and/or drug interventions in patients with diabetes mellitus or prediabetes can reduce the incidence of ischemic stroke and TIA events, and the recommended target of HbA1c treatment is <7%.
<b10> The hypoglycemic regimen should fully consider the clinical characteristics of the patient and the safety of the drug, formulate individualized blood glucose control goals, and be vigilant against the harm
caused by hypoglycemic events.

(4) While controlling blood glucose levels, patients with TIA should also carry out comprehensive and comprehensive management of other risk factors of
patients.

(5) TIA patients with insulin resistance can be given oral pioglitazone according to the individualized situation to prevent stroke, but pay attention to the risk of fractures and other risks
caused by treatment.
New evidence: studies have shown a significantly increased risk of stroke in patients with insulin resistance, and patients with acute ischemic stroke with insulin resistance have a poor post-thrombolytic prognosis
。 The newly published Insulin Resistance Intervention after Stroke (IRIS) study shows that in patients with non-diabetic ischemic stroke/TIA with insulin resistance, the diabetes drug pioglitazone is more likely than placebo to reduce the risk of
stroke or myocardial infarction (MI).
。 However, the treatment may cause the risk of weight gain, edema, and fractures requiring surgery or hospitalization, so individualized treatment
should be taken.

4.
Smoking

(1) It is recommended that patients with ischemic stroke or TIA with a history of smoking quit smoking
.

(2) It is recommended that patients with ischemic stroke or TIA avoid passive smoking and stay away from smoking places
.

(3) Possible effective means of smoking cessation include counseling, the use of nicotine substitute products or oral smoking cessation drugs
.

5.
Sleep apnea

(1) Encourage sleep respiration monitoring
in patients with TIA with conditions.

(2) The use of continuous positive airways pressure (CPAP) can improve the prognosis of patients with TIA with sleep apnea syndrome, and CPAP therapy
may be considered for these patients.

6.
Hyperhomocysteinemia

In patients with recent ischemic stroke or TIA with mild to moderate blood homocysteine levels, folic acid, vitamin B6, and vitamin B12 may reduce homocysteine levels
.
There is insufficient evidence to support that lowering homocysteine levels reduces the risk
of stroke recurrence.

(5) Secondary preventive drug compliance

1.
Drug adherence to secondary prevention in patients with ischemic stroke/TIA will affect the clinical prognosis
of stroke patients.

2.
Physician factors, patient factors, and medical system factors all affect the patient's adherence
to secondary prevention drugs.

3.
Standardized secondary prevention processes may increase the implementation rate
of secondary prevention drugs.