Note to myself: I’ve included the European Stroke Organization’s guidelines on how to determine TIA risk to decide when dual antiplatelet therapy is indicated and when monotherapy is indicated.
In this post I link to and excerpt from StatPearls‘ Transient Ischemic Attack, by Kiran K. Panuganti; Prasanna Tadi; Forshing Lui. Last Update: September 29, 2021.
All that follows is from the above resource.
A transient ischemic attack (TIA) is a medical emergency. It is defined as a transient episode of neurologic dysfunction due to the focal brain, spinal cord, or retinal ischemia, without acute infarction or tissue injury. The definition of a TIA has moved from time-based to tissue-based. A TIA typically lasts less than an hour, more often minutes. TIA can be considered as a serious warning for an impending ischemic stroke; the risk is highest in the first 48 hours following a transient ischemic attack. Differentiating transient ischemic attack from other mimicking conditions is important. Transient ischemic attacks are usually associated with a focal neurologic deficit and/or speech disturbance in a vascular territory due to underlying cerebrovascular disease. It is always sudden in onset. Evaluation of TIA should be done urgently with imaging and laboratory studies to decrease the risk of subsequent strokes. The subsequent risk of TIA or ischemic stroke can be stratified with a simple clinical measure. Immediate multimodality therapeutic interventions should be initiated. These will include aggressive treatment of blood pressure, high dose statin, antiplatelet therapy, blood sugar control, diet, and exercises. Specific underlying etiology needs to be managed accordingly. This treatment scheme may substantially reduce the risk of recurrent strokes or future TIA by at least 80%.
TIA subtypes, classified according to the pathophysiological mechanisms are similar to ischemic stroke subtypes. They include large artery atherothrombosis, cardiac embolism, small vessel (lacunar), cryptogenic, and uncommon subtypes such as vascular dissection, vasculitis, etc. The common risk factors for all TIA include diabetes, hypertension, age, smoking, obesity, alcoholism, unhealthy diet, psychosocial stress, and lack of regular physical activity. A previous history of stroke or TIA will increase substantially the subsequent risk of recurrent stroke or TIA. Among all risk factors, hypertension is the most important one for an individual as well as in a population.
TIA incidence in a population is difficult to estimate due to other mimicking disorders, but TIA incidence in the United States could be around half a million per year, and estimates are about 1.1 per 1000 in the United States population. The estimated overall prevalence of TIA among adults in the United States is approximately 2%. It has been shown that previous stroke history increases the prevalence of TIA. Few studies have shown that the majority of people who presented with initial stroke had prior TIA symptoms.
The pathophysiology of TIA depends on the subtype as follows. The common issue is the transient interruption of arterial blood flow to an area of the brain supplied by that particular artery.
- Large artery atherothrombosis. This may be intracranial or extracranial atherothrombosis. The mechanism may be a lack of blood flow distal to the site of arterial stenosis or an artery to artery embolism which is actually the more common mechanism.
- Small vessel ischemic diseases. The underlying pathology is either lipohyalinosis* or small vessel arteriolosclerosis. The commonest risk factor is hypertension followed by diabetes and age.
*See Lipohyalinosis, from Radiopaedia.
Last revised by Assoc Prof Frank Gaillard◉◈ on 08 Sep 2020
- Cardiac embolism. A clot in the cardiac chamber most commonly in the left atrium secondary to atrial fibrillation.
- Cryptogenic. This is usually a cortical pattern of ischemia without any identifiable large artery atherothrombosis or cardiac source of emboli. More recently it is often referred to as ESUS (embolic stroke of unknown source).
- Other uncommon causes such as arterial dissection or hypercoagulable states.
History and Physical
The 2009 AHA/ASA guidelines include “neuroimaging within 24 hours of symptom onset and further recommend MRI and diffusion-weighted MR imaging as preferred modalities.”
A head CT preferably with a CT angiogram is recommended if an MRI cannot be performed.
Brain MRI with diffusion-weighted imaging has a greater sensitivity than CT for detecting small infarcts in patients with TIA.
The practitioner should assess the patient’s cervicocephalic vasculature for atherosclerotic lesions using carotid ultrasonography/transcranial Doppler ultrasonography, magnetic resonance angiography, or CT angiography. These lesions are treatable. In candidates for carotid endarterectomy, carotid imaging should be performed within 1 week of the onset of symptoms.
Cardiac assessment should be done with ECG, Echocardiogram/TEE to find a cardioembolic source and the presence of patent foramen ovale, valvular disease, cardiac thrombus, and atherosclerosis. Holter monitor or more prolonged cardiac rhythm monitor in the outpatient setting is reasonable for patients with cortical infarct without any clear source of emboli, primarily to evaluate for paroxysmal atrial fibrillation.
Routine blood tests including complete blood count (CBC), PT/INR, CMP, FBS, lipid panel, urine drug screen, and ESR should be considered..
National Stroke Association has established guidelines for TIA evaluation as follows in 2006:
CBC = complete blood countCEA = carotid endarterectomyTCD = transcranial Doppler TEE = transesophageal echocardiogram TTE = transthoracic echocardiogram
The ABCD2 score is very important for predicting subsequent risks of TIA or stroke. The ABCD2 score was derived from providing a more robust prediction standard. The ABCD2 score includes factors including age, blood pressure, clinical symptoms, duration, and diabetes.
- Age: older than 60 years (1 point)
- Blood pressure greater than or equal to 140/90 mmHg on first evaluation (1 point)
- Clinical symptoms: a focal weakness with the spell (2 points) or speech impairment without weakness (1 point)
- Duration greater than 60 min (2 points), or 10 min to 59 min (1 point)
- Diabetes mellitus (1 point).
The 2-day risk of stroke was 0% for scores of 0 or 1, 1.3% for 2 or 3, 4.1% for 4 or 5, and 8.1% for 6 or 7. Most stroke centers will admit patients with TIA to the hospital for expedited management and observation if the score is 4 or 5 or higher. For those patients who have a lower score, expedited evaluation and management is still warranted. This expedited approach has been proven to improve the outcome. *
*Cutting S, Regan E, Lee VH, Prabhakaran S. High ABCD2 Scores and In-Hospital Interventions following Transient Ischemic Attack. Cerebrovasc Dis Extra. 2016;6(3):76-83. [PMC free article] [PubMed] [Reference list]
Treatment / Management
The main aim of treatment of TIA is to decrease the risk of subsequent stroke or TIA. Early treatment after a TIA can significantly reduce the risk of early stroke. Post TIA, the risk of stroke within 3 months has been reported to be around 20%, with approximately 50% of these strokes occurring within the first 2 days after the initial presentation. It is extremely important to evaluate the vessel status and look for atrial fibrillation when a patient comes with TIA. This will significantly reduce future strokes. Management of TIAs should focus on treating underlying etiologies.
10. Bath PM, Woodhouse LJ, Appleton JP, Beridze M, Christensen H, Dineen RA, Flaherty K, Duley L, England TJ, Havard D, Heptinstall S, James M, Kasonde C, Krishnan K, Markus HS, Montgomery AA, Pocock S, Randall M, Ranta A, Robinson TG, Scutt P, Venables GS, Sprigg N. Triple versus guideline antiplatelet therapy to prevent recurrence after acute ischaemic stroke or transient ischaemic attack: the TARDIS RCT. Health Technol Assess. 2018 Aug;22(48):1-76. [PMC free article] [PubMed] [Reference list]
11. Boulanger JM, Lindsay MP, Gubitz G, Smith EE, Stotts G, Foley N, Bhogal S, Boyle K, Braun L, Goddard T, Heran M, Kanya-Forster N, Lang E, Lavoie P, McClelland M, O’Kelly C, Pageau P, Pettersen J, Purvis H, Shamy M, Tampieri D, vanAdel B, Verbeek R, Blacquiere D, Casaubon L, Ferguson D, Hegedus Y, Jacquin GJ, Kelly M, Kamal N, Linkewich B, Lum C, Mann B, Milot G, Newcommon N, Poirier P, Simpkin W, Snieder E, Trivedi A, Whelan R, Eustace M, Smitko E, Butcher K. Canadian Stroke Best Practice Recommendations for Acute Stroke Management: Prehospital, Emergency Department, and Acute Inpatient Stroke Care, 6th Edition, Update 2018. Int J Stroke. 2018 Dec;13(9):949-984. [PubMed] [Reference list]
12. Ranta A, Dovey S, Gommans J, Tilyard M, Weatherall M. Impact of General Practitioner Transient Ischemic Attack Training on 90-Day Stroke Outcomes: Secondary Analysis of a Cluster Randomized Controlled Trial. J Stroke Cerebrovasc Dis. 2018 Jul;27(7):2014-2018. [PubMed] [Reference list]
Studies in the new millennium already confirmed the importance of expedited evaluation and treatment plus the polytherapy approach. The EXPRESS study in the UK has shown the importance of early intervention versus regular treatment by reducing 80% of the stroke risk.  Hackam et al did a meta-analysis in 2007 showing that combination of diet, exercise, antiplatelet, statin and antihypertensive therapy may↑ reduce the subsequent stroke by 80-90%.
More recent studies in China (CHANCE trial) and the multinational POINTE trail also confirmed dual antiplatelet with aspirin and clopidogrel for 3 weeks to 1 month followed by a single antiplatelet agent is the best scheme for antiplatelet therapy. *
The other part of the treatment will depend on the underlying etiology of the TIA. Revascularization is recommended for symptomatic cervical internal carotid artery stenosis of 70% or higher. Carotid endarterectomy may have a slight benefit to risk ratio compared with endovascular intervention and stenting. Whether to operate on patients with 50-69% stenosis will depend more on the surgeon’s complication rates given the vast improvement in the efficacy of aggressive medical therapy. SAPPRIS trial showed that endovascular Wingspan stenting of intracranial major arterial stenosis of 70-99% stenosis is not better than aggressive medical therapy alone. 
Oral anticoagulation is indicated for patients with atrial fibrillation or other sources of cardioembolic sources of TIA.
This section includes the ESO guidelines on when dual antiplatelet therapy is indicated.
*The European Stroke Organisation (ESO) guidelines on management of transient ischaemic attack [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Eur Stroke J. 2021 Jun;6(2):V. contain the following recommendations:
In patients with acute non-cardioembolic high risk TIA (ABCD2
score of 4 or more), we recommend short term dual antiplatelet therapy with aspirin and clopidogrel over monotherapy, subsequently followed by monotherapy.
Quality of evidence: High ΟΟΟΟ
Strength of recommendation: Strong for intervention ↑↑”
“About fifty patients need to be treated with aspirin and clopidogrel for three weeks
instead of monotherapy, to avoid one stroke.
Five hundred patients treated with aspirin and clopidogrel for three weeks compared with monotherapy will cause one to have a moderate to severe extracranial bleed.
Which patients this applies to:
These results apply to patients that have high risk TIAs according to the definition that was used in the CHANCE and POINT trials (ABCD2 score
“More studies are needed to establish if the results of these RCTs also apply to acute TIA patients with other features suggesting a high early risk of stroke (eg significant ipsilateral large artery disease eg carotid stenosis, intracranial stenosis, weakness or speech disturbance for greater than five minutes, recurrent events or with infarction on neuro-imaging).”
“Patients should have brain imaging to exclude acute intracranial bleeding, or other causes of symptoms, prior to starting DAPT.”
“Dual antiplatelet therapy with aspirin and clopidogrel should be started as soon as possible, and ideally within the first twenty-four hours.”
“When starting either aspirin or clopidogrel we suggest giving a single loading dose (at least 150 mg of aspirin, and 300 mg of clopidogrel) before switching to a daily maintenance dose.”
“The CHANCE study used clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first
21 days in comparison to placebo plus aspirin (75 mg per day for 90 days). All participants received open label aspirin at a clinician-determined dose of 75 to
300 mg on day 1. In the POINT study, patients in the clopidogrel plus aspirin group were given a 600-mg loading dose of clopidogrel, followed by 75 mg per day from day 2 to day 90, and a dose of open-label aspirin that ranged from 50 mg to 325 mg per day. Patients in the aspirin-only group received placebo that matched the appearance and taste of the clopidogrel tablets and the same range of aspirin doses. In the two groups, the dose of aspirin was selected by the treating physician. A dose of 162 mg daily for 5 days followed by 81 mg daily was recommended in the
POINT study to investigators. The first dose of trial medication was to be given as soon after randomization as possible.”
“Patients with high grade carotid stenosis and planned revascularisation were excluded from POINT, CHANCE and THALES.”
“In patients already taking either aspirin or clopidogrel alone, we suggest continuing with the maintenance dose of that medication, and loading with the other,
before continuing both medications at their maintenance dose.”
“Between 10 days and three weeks after starting dual antiplatelet therapy (DAPT) we suggest stopping one of the antiplatelet medications, and thereafter continuing the other antiplatelet as monotherapy based on local protocols and patient preference”
“Expert consensus statement
For patients with acute non-cardioembolic low risk TIA or
uncertain TIA diagnosis, 9/9 experts voted against using dual
antiplatelet therapy over monotherapy.”
“Our analyses of the currently available evidence show that early initiation of DAPT with aspirin and clopidogrel in high risk non-cardioembolic TIA
patients for up to 21 days reduces the risk of stroke recurrence over single antiplatelet treatment. These results apply to patients that have high risk TIAs
according to the definition that was used in the CHANCE and POINT trials (ABCD2 score of 4). More studies are needed to establish if the results of these RCTs also apply to TIA patients with other features suggesting a high early risk of stroke (e.g. significant ipsilateral large artery disease e.g. carotid stenosis, intracranial stenosis, weakness or speech disturbance for greater than five minutes, recurrent events or with infarction on neuro-imaging).”
“In clinical trials DAPT was started within 24 hours from symptoms onset in high-risk non-cardioembolic TIA (ABCD2 score of 4). The evidence base for maximal benefit-risk balance is with early and time limited (10 to 21 days) use of DAPT. An actively recruiting RCT (CHANCE-2) seeks to answer remaining questions regarding different DAPT regimens.92 This current guideline only addressed selected issues related to TIA management. However, it is important to highlight that TIA secondary prevention also includes medium and longer-term pharmacological and nonpharmacological measures that aim to control risk factors for late vascular events.”
“Although prompt and targeted evaluation for symptomatic carotid stenosis is
a key aspect of TIA evaluation, other investigations to determine TIA aetiology and risk factor are required, such as assessment for atrial fibrillation to guide optimal secondary prevention.
Now resuming the excerpts from StatPearls‘ Transient Ischemic Attack, by Kiran K. Panuganti; Prasanna Tadi; Forshing Lui. Last Update: September 29, 2021.
- Carotid artery dissection
- Meningococcal meningitis
- Multiple sclerosis
- Stroke, ischemic
- Stroke, hemorrhagic
- Subarachnoid haemorrhage
Risk Stratification Scores
To help physicians manage patients with a TIA, several risk stratification scores have been developed. One widely used score is the ABCD2 score:
A= Age more than 60 years / Score 1
B= SBP> 140 or DBP> 90 / Score 1
C= Clinical features:
Speech impairment without weakness / Score 1
Weakness with/without speech impairment / Score 2
More than 60 mins / Score 2
Between 10-59 mins / Score 1
D= Diabetes / Score 1
Patients with an ABCD2 score of 6-7 have an 8% risk of stroke within 48 hours
Patients with an ABCD2 score of less than 4 have a 1% risk of stroke within 48 hours
Even though scales are important in the evaluation of TIA, be aware that patients with critical carotid artery stenosis may some times present with a very low ABCD2 score.
Pearls and Other Issues
Differentiating other potential causes that mimic TIA is important since diagnosing and treating TIA early can potentially help in preventing a future stroke. Differential diagnosis of TIA includes but is not limited to vertigo, dizziness, seizures, headaches, bells palsy, drug withdrawal, dementia, electrolyte disorders, acute infections, syncope, and alcoholism.
Enhancing Healthcare Team Outcomes
Patients with a TIA often present to the emergency department or the primary caregiver. Because there is a real risk of a severe stroke, it is important that these patients are managed with an interprofessional team of healthcare workers. The triage nurse must be familiar with the symptoms of a TIA and when to call the neurologist. The early risk of stroke varies from 4-9% within 90 days and without treatment, the risk of a stroke within five years varies from 20-30%. At the same time, these patients also have the same risk factors for adverse cardiac events. Once a TIA has been diagnosed, the patient must be referred to a neurologist. At the same time, the patient should be educated about the importance of blood pressure control, discontinuing smoking and eating a healthy diet. Finally, the patient should be educated about the symptoms of a stroke and when to seek immediate medical assistance. (Level V)