Current Best Practice in TIA

ManagementDr Patrick Salvaris

Stroke Physician

SJOG Midland Hospital; Ambulance Victoria

Defining TIA

Outline:

Investigations

Imaging

Cardiac monitoring

Managing TIA in 2019

Prognosis

Defining a TIA….

Australian Stroke Foundation guidelines:

TIA is: Focal neurological symptoms due to focal ischaemia that have fully resolved AND should have urgent clinical assessment

Patients with symptoms that are present or fluctuating at time of initial assessment should be treated as having a stroke (and thus be sent to an emergency department)

Up to date TIA is now defined as:

A transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction

The end point, stroke, is biologic (tissue injury) rather than arbitrary (≥24 hours)

Therefore ischaemic stroke is: Infarction of central nervous system tissue

Historically

TIA was originally defined as:

A sudden onset of a focal neurologic symptom and/or sign lasting < 24 hours and caused by reversible cerebral ischemia.

However, this classic, time-based definition of TIA was inadequate for several reasons:

Risk of permanent tissue injury (infarction) even when focal transient neurologic symptoms.

50% of patients with classically defined TIA syndromes (<24 hours in duration) have corresponding ischemic lesions on MRI imaging

TIA Mimics:

Syncope

Migraine

Ocular pathology: Retinal detachment / glaucoma etc.

Chest pain / cardiac ischaemia with arm heaviness

Seizure

Hypoglycaemia

Bell’s palsy

Functional neurological disorder

And many more…….

Investigating TIAs

Investigations: Imaging:

CT brain

Urgent Carotid imaging (recommended within first 2 days):

If anterior circulation symptoms:

Either: CT angiogram or carotid Doppler (or MR angiography)

If posterior symptoms: CT angiogram

Weak recommendation that MRI, when available, increases diagnostic accuracy

Often a thorough HISTORY is most important

CT brain / MRI:

For diagnosis of a TIA: CT brain and MRI should NOT show an acute stroke

There may be underlying evidence of vascular disease:

Extra-cranial / intra-cranial atherosclerosis

White matter disease

Previous infarcts

Cerebral microbleeds (can represent hypertension / vascular damage / amyloid angiopathy)

Intracranial atherosclerosis

ICA stenosis:

Carotid imaging: For the majority of patients the decision to offer

intervention for a carotid stenosis depends mainly on degree of stenosis:

50-75%

75-99%

99% (near occlusion, evidence less robust for intervention)

BUT:

Increasingly we are evaluating plaque morphology either on CTA / Doppler / MRI (or a combination of modalities)

Especially in patients with borderline 50% stenosis

MRI carotid imaging is often challenging to interpret, depends on patient factors (lying still), but does add information to inform decision

MRI report as an example:

There is a dorsolateral eccentric predominantly lipid rich core plaque of the left carotid bulb and the proximal left ICA with MRI features strongly suggestive of plaque rupture - plaque instability.

The plaque causes approximately 55-60% luminal narrowing of the proximal left internal carotid artery

Cardiac monitoring

Challenges:

ECG and 24 hour holter often are INSUFFICIENT to diagnose:

Paroxysmal atrial fibrillation

Heart block

Significant bradycardia / sinus node abnormality

Echocardiogram: Structural abnormalities greatly increase the risk of AF

Especially enlarged left atrial dimensions

Valvular disease, especially mitral valve disease, increases risk for AF

Options:

If high risk for AF / heart block then further Ix is highly desirable

In cases where syncope occurs / suspicion of heart block a cardiology review and consideration for implantable loop recorder is suitable

Patients with paroxysmal AF / chronic AF without stroke / TIA should routinely be offered anticoagulation by their GPs

Aspirin DOES NOT reduce AF stroke risk

The AF story: Complexities

The AF story: Complexities 1965 adults with paroxysmal AF, mean age 69yo, 880

(45%) were women, median CHA2DS2-VASc score = 3.

Median burden of atrial fibrillation was 4.4%.

After adjusting for CHA2DS2-VASc stroke risk scores:

Highest tertile of AF burden (>11.4%) was associated with > 3x increased rate of thromboembolism while not taking anticoagulants vs combined lower 2 tertiles of AF burden.

A greater burden of atrial fibrillation is associated with a higher risk of ischemic stroke independent of known stroke risk factors in adults with paroxysmal atrial fibrillation.

Left atrial size

Left atrial volume index (LAVI) were greater in patients with cardoembolic stroke vs non-cardioembolic stroke:

41mL/m2 vs 28.6mL/m2

Among 99 patients with ESUS (embolic stroke of unknown source) 18.2% had AF detected

LAVI was independently associated with AF detection

Odds ratio: 1.09

More data is coming……

AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke (ARCADIA) trial, completion April 2022

Aspirin vs apixaban in preventing stroke recurrence after cryptogenic stroke

Practice points:

Patients with “resolved AF” still have an elevated stroke risk

Of 11,000 patients with “resolved AF” vs 22,000 without AF…..

During a median of 3 years rate of stroke / TIA with resolved AF was 59% higher VS without previous AF

Only 17% of patients had current anticoagulant prescription

WE MUST DO BETTER TO ANTICOAGULATE PATIENTS WITH AF AND ALSO PAROXYSMAL AF

Management Dual antiplatelets for 3 weeks with aspirin +

clopidogrel for TIA has been shown to reduce recurrence and limit time / bleeding risk associated with dual antiplatelets

Carotid disease carotid endarterectomy / stenting

Atrial fibrillation anticoagulation

Secondary prevention:

Statin, BP management, smoking cessation

POINT trial outcomes: A total of 4881 patients were enrolled at 269

international sites.

The trial was halted after 84% of the anticipated number of patients had been enrolled because the data and safety monitoring board had determined that: The combination of clopidogrel and aspirin was

associated with BOTH a:

Lower risk of major ischemic events AND

A higher risk of major haemorrhage than aspirin alone at 90 days.

POINT outcomes:

Major ischemic events occurred in:

121 of 2432 patients (5.0%) receiving clopidogrel plus aspirin vs

160 of 2449 patients (6.5%) receiving aspirin plus placebo (hazard ratio, 0.75; 95% CI 0.59 to 0.95; P = 0.02), with most events occurring during the first week after the initial event.

Major haemorrhage occurred in 23 patients (0.9%) receiving clopidogrel plus aspirin and in 10 patients (0.4%) receiving aspirin plus placebo (hazard ratio, 2.32; 95% CI, 1.10 to 4.87; P = 0.02).

Statin use If a patient has atrial fibrillation as a cause of TIA /

stroke I do not prescribe a statin purely on the basis of the TIA / stroke

In older patients > 90 years of age, consider the benefit in the trial occurred only AFTER 2 years of treatment

Those with high cholesterol / family history of lipid disorder should be encouraged to take statins continuously and IF side-effects trial patients on other statins (e.g. rosuvastatin vs atrovastatin)

Diabetics should also be considered for a fibrate If TG > 2

SPARCL study:

Eligible patients were men and women over 18 years of age who had had an ischemic or haemorrhagic stroke or a TIA (diagnosed by a neurologist within 30 days after the event) 1 to 6 months before randomization

The exclusion criteria included:

Atrial fibrillation

Other cardiac sources of embolism

Subarachnoid haemorrhage.

The absolute difference in Kaplan–Meier rates at five years was 2.2%

High-Dose Atorvastatin after Stroke or Transient Ischemic Attack

Fitness:

Cardiovascular fitness and risk of stroke and death

Oslo Ischemia Study analysed 1403 healthy men between 40-59 years in 1972 to 1975 and followed up for a mean of 23.6 years

If fit at baseline AND became unfit VS remaining fit:

HR 2.35 and 1.74 for risk for ischaemic stroke and death

If unfit at baseline AND became fit VS remaining unfit:

HR 0.4 and 0.66 becoming fit showed significantly lower risk of stroke and death

Depression 5095 people studied from 1993 to 2005 who were free of

depression at baseline were assessed whether occurrence of a TIA boosted risk of later life depression.

Population study people aged > 55yrs

BASELINE: 32% had history of depression

FOLLOW UP: 40 depressive syndromes occurred, 25% met DSM-IV criteria for depressive disorders

Outcomes:

TIA was associated with 68% increase risk of depression and 2.5 fold increase in DSM-IV defined depressive disorders.

As the number of TIAs increased, the risk of depressive syndromes increased by 45%

Reinforces the seriousness of TIA and neurological damage

Prognosis following a TIA:

Prognosis despite best medical management: In a 5-year study involving patients who had a TIA or minor

stroke, the rate of cardiovascular events including stroke in a selected cohort was:

6.4% in the first year

6.4% in the second through fifth years

Total: 12.8% over 5 years

Total stroke at 5 years: 9.5%

“Among patients who had had a TIA or minor stroke, we observed a sustained risk of cardiovascular events over a period of 5 years, with half of the events occurring during years 2 through 5. There may be potential for reducing recurrent strokes by ongoing secondary prevention measures.”