Recommendations
Urgent
Treat all patients with suspected transient ischaemic attack (TIA) urgently.[40]
The risk of recurrent stroke is up to 10% in the first 7 days following a TIA.[42]
Give a loading dose of aspirin immediately, unless contraindicated, to patients with suspected TIA (in the accident and emergency department or in the community).[9][40]
Give a proton-pump inhibitor to anyone with dyspepsia associated with aspirin use.[9]
Give clopidogrel as an alternative to aspirin in patients who are allergic or intolerant to aspirin.
Refer the patient immediately for specialist assessment and investigation to a TIA clinic (or suitable alternative) to be seen within 24 hours of onset of symptoms.[9][40] Assessment should be conducted by a stroke specialist clinician in a neurovascular clinic or an acute stroke unit.[40]
Key Recommendations
Start dual antiplatelet therapy with either aspirin and clopidogrel for 21 days, or aspirin and ticagrelor for 30 days, in patients presenting within 24 hours of TIA and with a low risk of bleeding. For patients who are not appropriate for dual antiplatelet therapy, give a clopidogrel loading dose followed by a daily maintenance dose.[40]
A proton-pump inhibitor should be considered for concurrent use with dual antiplatelet therapy to reduce the risk of gastrointestinal haemorrhage.[40]
Give a proton-pump inhibitor to anyone with dyspepsia associated with aspirin use.[9]
After completion of dual antiplatelet treatment (or clopidogrel loading dose where dual treatment is inappropriate), for long-term prevention of vascular events in people with TIA without paroxysmal or permanent atrial fibrillation, single antiplatelet treatment should be used with clopidogrel recommended as standard treatment.[40] Aspirin should be used for those who are unable to tolerate clopidogrel.
Give an anticoagulant with a rapid onset of action to patients with paroxysmal, persistent, or permanent atrial fibrillation or atrial flutter as soon as intracranial bleeding or other contraindications (such as severe hypertension - clinic blood pressure of 180/120 or higher, which should be treated first) are excluded.[40]
Start high-intensity statin therapy immediately, unless contraindicated, in all patients (independent of baseline low-density lipoprotein) for long-term secondary prevention.[40]
Treat all patients with suspected TIA urgently.[40] Consider all people with suspected TIA to be at high risk of having a stroke.[9]
Aspirin and immediate referral for specialist assessment
Give a loading dose of aspirin immediately, unless contraindicated.[9][40]
Give a proton-pump inhibitor to anyone with dyspepsia associated with aspirin use.[9]
Give clopidogrel as an alternative to aspirin in patients who are allergic or intolerant to aspirin. This is standard practice.
Do this before the patient has been assessed by a specialist.
Refer the patient immediately to a TIA clinic (or suitable alternative) to be seen within 24 hours of onset of symptoms following your initial assessment.[9][40] Assessment should be conducted by a stroke specialist clinician in a neurovascular clinic or an acute stroke unit.[40] For more information see Aspirin and immediate referral for specialist assessment under Diagnosis recommendations.
Evidence: Aspirin administration before specialist assessment
Early aspirin probably reduces the risk of recurrent stroke in patients with suspected TIA without increasing the risk of intracranial haemorrhage; however, the evidence is from indirect populations.
Due to debate on the timing of aspirin administration in patients with suspected TIA the UK National Institute for Health and Care Excellence (NICE) carried out an evidence review in 2019. NICE looked at the evidence for the efficacy and safety of early aspirin, prior to someone being seen by an expert.[59] The review included one study, an individual patient data (IPD) meta-analysis, which compared aspirin with placebo (11 studies, n=31844).[60]
Only one post-hoc subgroup analysis was included in the NICE review as the rest of the evidence was too indirect.
This subgroup only included people given aspirin within 48 hours of the index event (2 randomised controlled trials [RCTs]: the Chinese Acute Stroke Trial [CAST] and the International Stroke Trial [IST]).
The population in this subgroup analysis was still indirect as it included people with confirmed TIA or minor ischaemic stroke; aspirin was given up to 48 hours after the index event, including in secondary care, and not necessarily at first contact with a healthcare professional.
From this indirect evidence, aspirin seemed to reduce the risk of recurrent stroke.
Risk was 3.2 times less at 3 days following the event and 1.5 times less at 14 days with aspirin compared with placebo (1 RCT, n=28552).
This was also the case for a subgroup analysis in those with mild ischaemic stroke at 14 days (n=8464; relative risk 0.5, 95% CI 0.33 to 0.76).
There was no difference at 24 hours (1 RCT, n=28552; hazard ratio [HR] 0.94, 95% CI 0.67 to 1.32), except in people who had been given aspirin prior to randomisation (1 RCT, n=3292; HR 0.31, 95% CI 0.11 to 0.87).
All outcomes were very low quality as assessed by GRADE.
No evidence was available from the IPD for risk of mortality, intracranial haemorrhage, major bleeding complications, functional outcomes, or quality of life.
Due to the importance of avoiding an increased risk of intracranial haemorrhage NICE considered additional evidence from the IPD study.
NICE noted that, in general, intracranial haemorrhage is rarely a cause of TIA symptoms and is only the cause of 5% of minor strokes.
In people with minor stroke given low-dose aspirin, there was no increase in the risk of intracerebral haemorrhage at 12 weeks (3/4125 with aspirin vs. 5/4137 in the control group).
The guideline development group members decided, based on this and their clinical experience, that it would therefore be safe for any healthcare professional to give a loading dose of aspirin as a one-off prior to specialist referral.
Secondary prevention
Give secondary prevention as soon as possible to all patients after the diagnosis of TIA is confirmed.[9][40]
Antiplatelet therapy
Start dual antiplatelet therapy with either aspirin and clopidogrel for 21 days, or aspirin and ticagrelor for 30 days, in patients presenting within 24 hours of TIA and with a low risk of bleeding. For patients who are not appropriate for dual antiplatelet therapy, give a clopidogrel loading dose followed by a daily maintenance dose.
A proton-pump inhibitor should be considered for concurrent use with dual antiplatelet therapy to reduce the risk of gastrointestinal haemorrhage.[40]
Give a proton-pump inhibitor to anyone with dyspepsia associated with aspirin use.[9]
After completion of dual antiplatelet therapy (or clopidogrel loading dose where dual treatment is inappropriate), for long-term secondary prevention of vascular events in patients without paroxysmal or permanent atrial fibrillation, single antiplatelet treatment should be used with clopidogrel as standard treatment.[40] Aspirin should be used for those who are unable to tolerate clopidogrel.[40]
The European Stroke Organisation (ESO) recommends that clopidogrel and aspirin should be combined in adults with a high-risk TIA (ABCD2 score ≥4) within 24 hours of the TIA. The ESO recommends that dual therapy should be continued for 21 days followed by single antiplatelet therapy.[61] In March 2021, the ESO guidelines made a weak recommendation based on moderate-quality evidence for 30 days of dual antiplatelet therapy with ticagrelor and aspirin in people with high-risk TIA (ABCD2 score of 6 or more or other high-risk features, defined as either intracranial atherosclerotic disease or at least 50% stenosis in an internal carotid artery that could account for the presentation) in the past 24 hours.[61] The ESO stated that this regimen should be considered as an alternative to clopidogrel plus aspirin, particularly in people known to be intolerant of clopidogrel.[61] The use of dual antiplatelet therapy with aspirin and ticagrelor is also supported by the European Society of Cardiology.[62] However, an application to the European Medicines Agency (EMA) to change the marketing authorisation of ticagrelor to include the prevention of stroke in adults who have had a mild to moderate ischaemic stroke or high-risk TIA was withdrawn in December 2021. Based on trial data and the company's response to its questions, the EMA expressed concern that the benefits of short-term treatment with ticagrelor plus aspirin in preventing stroke in these patients did not clearly outweigh the risks of fatal and non-fatal bleeding.
Evidence: Dual antiplatelet therapy with aspirin and clopidogrel
Guidelines from the National Clinical Guideline for Stroke for the UK and Ireland and from the European Stroke Organisation recommend to consider dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in patients presenting with TIA and with a low risk of bleeding, followed by single antiplatelet therapy, if there are no contraindications.[40][61] See panel below for evidence supporting DAPT with aspirin and ticagrelor.
The National Clinical Guideline for Stroke for the UK and Ireland cites the CHANCE and POINT trials to support the use of DAPT with aspirin and clopidogrel.[63][64][65]
Guidance from the European Stroke Organisation additionally cites the FASTER trial.[61][66]
CHANCE[63]
This trial was conducted at 114 centres in China and recruited 5170 patients.
In patients with high-risk TIA or minor ischaemic stroke (National Institutes of Health Stroke Scale [NIHSS] 0-3), DAPT with clopidogrel plus aspirin started within 24 hours of onset for 21 days resulted in a significant reduction in ischaemic stroke over the first 90 days from 11.7% with aspirin plus placebo versus 8.2% with aspirin plus clopidogrel (hazard ratio [HR] 0.68, 95% CI 0.57 to 0.81; P<0.001).
DAPT with clopidogrel plus aspirin did not increase the risk of moderate or severe haemorrhage in comparison with aspirin alone.[63] The benefit persisted during 1-year follow-up.[67]
POINT[64]
This trial recruited 4881 patients with high-risk TIA or minor ischaemic stroke (NIHSS 0-3) across 269 international sites in North America, Europe, Australia, and New Zealand.
DAPT with clopidogrel plus aspirin, started within 12 hours of onset and continued for 90 days, resulted in a significant reduction of ischaemic stroke from 6.5% with aspirin alone versus 5.0% with the aspirin plus clopidogrel (HR 0.75, 95% CI 0.59 to 0.95; P=0.02), with most events occurring during the first week after the initial event.
The trial was stopped early because of a lower risk of major ischaemic events and a higher increase in major haemorrhage (mostly gastrointestinal) in the DAPT group, with an absolute risk increase of 0.5%. There was no difference in fatal haemorrhage or intracranial haemorrhage.
The higher rate of bleeding in the POINT trial compared with the CHANCE trial was postulated to be due to a shorter duration of combined treatment in the CHANCE trial (21 days in the CHANCE trial vs. 90 days in the POINT trial) and differences in the metabolism of clopidogrel in Asian versus non-Asian persons.[68]
The National Clinical Guideline for Stroke for the UK and Ireland and the European Stroke Organisation cite a pooled analysis of these two trials, finding benefit of DAPT with aspirin plus clopidogrel in this population was confined to the first 21 days.[69]
FASTER[66]
This trial, conducted in patients in North America, compared DAPT with aspirin and clopidogrel with aspirin alone within 24 hours of symptom onset in patients with TIA or minor ischaemic stroke.
At 90 days, it found a 7.1% stroke rate on combined therapy versus 10.8% on aspirin alone (risk ratio [RR] 0.7, 95% CI 0.3 to 1.2; absolute risk reduction -3.8%, 95% CI -9.4 to 1.9; P=0.19).
There was a statistically non-significant increase in symptomatic bleeding with aspirin and clopidogrel compared with aspirin alone.
A 2018 systematic review of these three randomised placebo-controlled trials (CHANCE, FASTER, POINT; n=10,447), found:[70]
Compared with aspirin alone, DAPT (clopidogrel and aspirin) started within 24 hours of high-risk TIA or minor ischaemic stroke reduced the risk of non-fatal recurrent stroke by about 20 in 1000 population at 90 days (RR 0.70, 95% CI 0.61 to 0.81; absolute reduction 1.9%)
There was a possible increase in moderate to severe extracranial bleeding of 2 per 1000 population.
The reviewers concluded that discontinuation of dual antiplatelet therapy within 21 days and possibly as early as 10 days of initiation was likely to maximise benefit and minimise harm.
Evidence: Dual antiplatelet therapy with aspirin and ticagrelor
In its guidance on dual antiplatelet therapy (DAPT), the National Clinical Guideline for Stroke for the UK and Ireland also recommends aspirin and ticagrelor if there are no contraindications (as an equal alternative to dual treatment with aspirin and clopidogrel) for 30 days in patients presenting with TIA and with a low risk of bleeding.[40]
This guidance is supported by the THALES randomised controlled trial of 11,016 patients with high-risk TIA or minor ischaemic stroke (National Institutes of Health Stroke Scale [NIHSS] ≤5), none of whom received thrombolysis or thrombectomy or required anticoagulation.[65]
THALES demonstrated that, compared with aspirin plus placebo, dual treatment with ticagrelor and aspirin reduced the risk of disabling stroke or death within 30 days.
The primary composite outcome of recurrent stroke or death occurred in 303 patients (5.5%) in the dual antiplatelet group and 362 patients (6.6%) in the aspirin plus placebo group (hazard ratio [HR] 0.83, 95% CI 0.71 to 0.96; P=0.02).
Ischaemic stroke occurred in 276 patients (5.0%) in the ticagrelor plus aspirin group and 345 patients (6.3%) in the aspirin plus placebo group (HR 0.79, 95% CI 0.68 to 0.93; P=0.004).
Severe bleeding was more frequent with ticagrelor plus aspirin (0.5%) than with aspirin plus placebo (0.1%) (HR 3.00, 95% CI 1.74 to 9.14; P=0.001), including intracranial haemorrhage (0.4% with ticagrelor plus aspirin vs. 0.1% with aspirin plus placebo [HR 3.33, 95% CI 1.34 to 8.28; P=0.01).
Lipid-lowering therapy
Start high-intensity statin therapy immediately (unless contraindicated) in all patients independent of baseline low-density lipoprotein for long-term secondary prevention.[40]
Consider increasing the statin intensity or dose if the patient is not currently taking a high-intensity statin at the maximum tolerated dose.[38]
Use an alternative statin at the maximum tolerated dose if high-intensity statin therapy is unsuitable or not tolerated.[40] Check local protocols for recommended alternatives in your region.
Patients with atrial fibrillation
Give an anticoagulant with a rapid onset of action to patients with TIA and paroxysmal, persistent, or permanent atrial fibrillation or atrial flutter once intracranial bleeding and other contraindications (such as severe hypertension - clinic blood pressure of 180/120 or higher, which should be treated first) are excluded. Cerebral microbleeds (regardless of number or distribution) need not preclude the use of such treatment.[40]
Anticoagulation should include measures to reduce bleeding risk, using a validated tool to identify modifiable risk factors.[40]
Give a direct oral anticoagulant (DOAC) as first-line treatment for people with TIA due to non-valvular atrial fibrillation.[40]
Give adjusted-dose warfarin to people with TIA due to valvular/rheumatic atrial fibrillation or with mechanical heart valve replacement, and those with contraindications or intolerance to DOAC treatment (target INR 2.5, range 2.0 to 3.0) with a target time in the therapeutic range of greater than 72%.[40]
For people with cardioembolic TIA for whom treatment with anticoagulation is considered inappropriate because of a high risk of bleeding:[40]
Do not use antiplatelet treatment as an alternative when there are absolute contraindications to anticoagulation (e.g., undiagnosed bleeding)
A left atrial appendage occlusion device may be considered as an alternative, provided the short-term peri-procedural use of antiplatelet therapy is an acceptable risk.
For people with cardioembolic TIA for whom treatment with anticoagulation is considered inappropriate for reasons other than the risk of bleeding:[40]
Antiplatelet treatment may be considered to reduce the risk of recurrent vaso-occlusive disease.
People who initially present with recurrent TIA or stroke should receive the same antithrombotic treatment as those who have had a single event. More intensive antiplatelet therapy or anticoagulation treatment should only be given as part of a clinical trial or in exceptional clinical circumstances.[40] Seek specialist advice for alternatives in patients with contraindications to anticoagulants with a rapid onset. See New-onset atrial fibrillation.
Patients with symptomatic carotid stenosis
Following specialist assessment, if a patient with TIA is considered to be a candidate for carotid intervention they should have carotid imaging performed within 24 hours of assessment. This includes carotid duplex ultrasound or either computed tomographic (CT) angiography or magnetic resonance (MR) angiography.[40]
Patients with stable neurological symptoms and symptomatic carotid stenosis of 50% to 99% according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria will be assessed and referred by the specialist for urgent carotid endarterectomy to a specialist service meeting national standards.[9][40] See Carotid artery stenosis.
Patients with symptomatic carotid stenosis of less than 50% according to the NASCET criteria, or less than 70% according to the European Carotid Surgery Trial (ECST) criteria, should not be referred for surgery.[9][40]
At discharge from hospital, advise the patient not to drive for 4 weeks due to their early risk of having a stroke, and to return to the accident and emergency department if they develop any new neurological symptoms.
After the patient has been seen in the TIA clinic or suitable alternative, the specialist will contact the patient’s general practitioner.
The general practitioner will be informed of the patient’s TIA and given recommendations regarding long-term secondary prevention (including antihypertensive therapy and diet and lifestyle advice).
See Secondary prevention.
How to record an ECG. Demonstrates placement of chest and limb electrodes.
How to take a venous blood sample from the antecubital fossa using a vacuum needle.
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