Transient Ischaemic Attack is an Emergency: Think about Best Current Stroke Prevention Options

A medical emergency is a condition that requires immediate action to prevent severe disability or death. Despite the apparent well-being of the patient after the ictus, transient ischaemic attack (TIA) is an emergency.

Transient ischemic attack has long been known as a precursor to major ischaemic stroke. In a recent meta-analysis, the risk of stroke after TIA was estimated to be 3.1%, 6.4% and 8.7% at 2 days, 1 month and 3 months, respectively. In the same review, using only data from studies using active outcome ascertainment, the risk was estimated at 9.9%, 13.4% and 17.3% for the same time points (1). Half of the 90-day stroke risk occurs in the first 2 days after TIA, and 76% of strokes required hospitalization (2). The FASTER trial provided the first prospective evaluation of early risk of stroke after TIA in a randomized trial, enrolling patients within 24 h of symptom onset. In this selected population of minor stroke or TIA patients with weakness or speech disturbance for more than five minutes as part of their clinical event, the 90-day risk of stroke was 8.9% across treatment groups and the median time to the event was only 1 day (3). Thus, TIA portends a serious risk of early major stroke and the time window for intervention is short.

Immediately after the resolution of neurological deficits, a patient has the whole high risk period before him. For patients with rapidly improving or fully resolved deficits, several reports indicate a high risk of deterioration and permanent deficits, especially for patients with a marked initial improvement on the National Institute of Health Stroke Scale (NIHSS) (4). Indeed, as a general rule, the risk of stroke and new neurological deficits is higher in patients with TIA than among patients with completed stroke, indicating an unstable ongoing process. In parallel, the long-term prognosis after TIA is grave. The combined risk of stroke, MI or death in the first year after TIA has been estimated at 22%, with the composite outcome primarily driven by the high stroke rate (5). A meta-analysis estimated a similar 2.2% annual rate of MI and a 2.1% annual rate of non-stroke vascular death after TIA (6).

The concept of TIA has evolved, and a new definition has been proposed (7). The current WHO definition states that TIA is a sudden episode of neurological dysfunction, of vascular origin, lasting < 24 h. It is suggested that the diagnosis of TIA be defined by a brief episode of neurological dysfunction caused by focal brain or retinal ischaemia, with clinical symptoms typically lasting < 1 h, and without evidence of acute infarction. As a corollary, imaging evidence of ischaemia, either on computed tomography (CT) or more commonly on diffusion weighted magnetic resonance (MR) imaging, implies a stroke regardless of the clinical duration of symptoms. This definition has not been formally adopted by the stroke community, but it is our opinion that it is a biologically sensible approach and where MR imaging is available, this new definition is being adopted in routine practice.

On a practical basis, however, the clinical TIA syndrome is sufficient in itself to mandate immediate evaluation, even more so if there is biological proof of an infarct. Importantly, there is little distinction between TIA (where there is full and complete resolution of all symptoms) and minor stroke. Few physicians and even patients, distinguish between full resolution and residual minor paresthesiae or very mild weakness. We believe that it is unlikely that published studies on TIA, do not include minor stroke as well.

Characteristics of the TIA patients and the symptomatic event allow stratification of a patient's stroke risk as low, moderate or high risk. The recently reported ABCD2 score identified the possibility of estimating risk based on age, blood pressure, presence of diabetes, duration and clinical features of the event (8, 9). Magnetic resonance imaging (MRI) can both support the diagnosis of an ischaemic event and further stratify the risk of stroke. A lesion identified by diffusion weighted MR scan performed within 24 h of symptom onset carried 2.6 times the risk of a new stroke within 90 days compared with no lesion in a selected population of paretic or aphasic TIA or minor stroke patients (NIHSS 3 or less) (10). Aetiology is relevant: data from the medical treatment group of the NASCET trial revealed a 5.5% risk of stroke at two days and a 20.1% risk at 90 days from symptom onset among patients with hemispheric TIA and ipsilateral carotid stenosis (any degree) (11).

Conversely, patients with sensory symptoms only, numbness, isolated dizziness or vertigo, and no stroke risk factors are not at high risk. Some of these patients may not, in fact, have had ischaemia as the underlying cause of their neurological symptoms. Stroke mimics such as migraine, somatization, seizure, metabolic disturbance, drug use may be responsible, all of which have a relatively benign prognosis (12).

The long-term preventive treatments for stroke and TIA patients are relatively better studied. A quantitative modelling study using data from the meta-analysis of randomized controlled trials evaluating the five proven secondary preventive therapies (diet, exercise, aspirin, statins and antihypertensive therapy) after stroke or TIA estimated a 80% relative risk reduction of recurrent stroke, Myocardial infarction or vascular death over 5-years (13). However, akin to acute coronary syndromes or acute limb ischaemia, the risk-benefit equation is different acutely. Treatments for acute TIA are poorly studied to date and the best treatments in the first 2–4 weeks after TIA are unknown. In the first randomized study of hyper acute stroke prevention after TIA or minor stroke, the FASTER pilot study showed an approximately 4% (non-significant) risk reduction in the risk of stroke with clopidogrel and acetylsalicylic acid (ASA) vs. ASA alone (3). Whatever the best strategy, the early risk of stroke after TIA and the efficacy of secondary preventive therapies started after 2–4 weeks indicates a large window of opportunity to save strokes if we treat in the early period.

The EXPRESS and SOS-TIA trials gave us a glimpse of how much we can do when we apply powerful therapeutic measures in the early, high-risk period after TIA and minor stroke. In the SOS-TIA study, the implementation of a 24 h-7 days a week TIA clinic allowing to assess patients within short range of symptom onset (53% in < 24 h) and begin appropriate treatment immediately resulted in a very low 90 days risk of stroke (1.24% for the study population) compared with a historical control (estimate from the ABCD (2) score of 5.96%) (14). The EXPRESS study, using a prospective before and after comparison design evaluating the effect of early assessment and treatment with existing preventive strategies of patients with TIA and minor stroke on stroke risk within the Oxford vascular population-based incidence study, revealed a 80% relative risk reduction of stroke in the 90 days following the first contact with medical services, with an absolute risk reduction of 8.2% (10.3% vs. 2.1%) (15). Caution is warranted in making definitive conclusions from observational cohort studies comparing to historical controls. The effect size may be overestimated.

Best current stroke prevention options will vary by stroke mechanism. Early assessment also means early investigation. The ideal method to investigate the TIA patient is multi-modal MRI, due to its sensitivity to small volume ischaemia and potential for ‘one-stop shopping’ imaging of the neurovasculature, but this modality is not always available for high-throughput imaging. At minimum, patients with TIA should have same-day CT of the head and carotid artery imaging with ultrasound or CT angiography. Patients should receive antiplatelet therapy. Whether or not admission to hospital is required remains uncertain (16). Future trials in this area will help us to elucidate the best methods for hyper acute stroke prevention. The best stroke is the one that never happens.