NPC Archive Item: Treat TIAs and minor strokes urgently

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Rothwell PM et al. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. Lancet Neurology Published early online 9th October 2007

What is the background to this?
Stroke describes the rapidly developing signs of focal or global disturbance of cerebral functions which arise from vascular problems, mainly cerebral infarction. These last more than 24 hours and/or may result in death. Transient ischaemic attack (TIA) is a clinical syndrome characterised by an acute loss of focal cerebral or ocular function with symptoms lasting less than 24 hours. It is thought to be due to inadequate cerebral or ocular blood supply. The risk of stroke after a TIA may be as high as 20% within the first month, with the greatest risk in the first 72 hours. You can find more information about stroke and TIA and secondary prevention of stroke on the stroke section of NPC.

What does this study claim?
Earlier initiation of existing treatments after TIA or minor stroke (by making access to a specialist clinic easier) was associated with an 80% relative risk reduction (RRR) in the risk of early recurrent stroke (within 90 days), among patients managed in outpatient care (absolute risk reduction 8.2%, NNT=12 , P<0.0001).

How does this relate to other studies?
The most up-to-date guidelines on the treatment of stroke (all aspects) were issued by the Royal College of Physicians (RCP) in 2004. The RCP guideline recommends that patients with TIA or with a stroke but having made a good recovery should be assessed and investigated in a specialist service as soon as possible within seven days of the incident. Patients with stroke should be assessed by an experienced clinician and have brain imaging undertaken within 24 hours (at most) of onset of symptoms (and even sooner in some circumstances). In patients with a TIA, once all symptoms have resolved, aspirin 300 mg daily should be given immediately and continued until a definitive management plan has been established (note that if symptoms are still present, it is important to exclude the possibility of a haemorrhagic stroke). If patients have a previous history of gastrointestinal (GI) side-effects to aspirin, or are at particular risk of GI problems (e.g. already taking an NSAID), gastro-protection with a PPI seems reasonable.

This study suggests that it is beneficial to make access to specialist care as easy and rapid as possible – by making direct referral without the need for appointment – as well as starting treatment with the minimum of delay.

A paper also published early online in Lancet Neurology this week (the FASTER study) appears to show that prompt treatment with clopidogrel plus aspirin within 24 hours of TIA or minor stroke has no significant effect on reducing the risk of recurrent stroke compared to aspirin alone. The trial was stopped early due to a failure to recruit patients at the prespecified minimum enrolment rate. This may have reduced the power of the study to detect a difference. Nevertheless, this result is in keeping with the MATCH study, which looked at longer term secondary prevention. In the MATCH study, patients who had suffered a TIA or ischaemic stroke within the previous three months, and who had at least one additional cardiovascular risk factor were randomised to receive either clopidogrel plus aspirin (both 75mg daily) or clopidogrel 75mg daily alone. Combination therapy did not reduce the risk of the primary endpoint (a composite of ischaemic stroke, myocardial infarction, vascular death and rehospitalisation for an acute ischaemic event). However, patients taking the combination were twice as likely to experience significant life-threatening bleeds as those taking clopidogrel alone.

So what?
Very rapid access to specialist care and prompt initiation of treatment can reduce the risk of stroke in people who have had a TIA, and further stroke in those who have had a minor stroke. The authors of this paper suggest that, extrapolated across the UK, their findings would equate to the prevention of nearly 10,000 strokes per year. Quite apart from the costs to individual patients and their families and carers, the health care costs of treating stroke are huge. The Faster study confirms that clopidogrel in combination with aspirin has an extremely limited role in the management of patients who have had a stroke or TIA – see the stroke section of NPC for details.

All health professionals should recognise that stroke and TIA are neurological emergencies. The Stroke Association calls stroke “brain attack” and promotes the Face Arm Speech Test (FAST) to help with recognition of stroke and TIA:

Facial weakness – can the person smile? Has their mouth or eye drooped?
Arm weakness – can the person raise both arms?
Speech problems – can the person speak clearly and understand what you say?
Test all three symptoms.

If stroke or TIA is suspected, the patient needs urgent medical attention. Clinicians should consider the RCP guidelines described above, that once symptoms have resolved after a TIA, aspirin 300 mg daily should be given immediately and continued until a definitive management plan has been established (note that if symptoms are still present, it is important to exclude the possibility of a haemorrhagic stroke).

Study details

Design: Prospective before-and-after study.

Patients: 1278 patients in the Oxford Vascular Study (OXVASC) who presented with stroke or TIA. Patients were well matched, except that in phase 2 more patients were taking statins at study entry.

Intervention and Comparison: In the first phase (April 1st 2002 to September 30th 2004), a daily specialist clinic was established where GPs could refer patients with suspected TIA and minor stroke for an appointment by fax. Treatments were not started in the clinic but recommendations were made to the patients’ GPs. In the second phase (October 1st 2004 to March 31st 2007) no appointments were necessary and treatment was started in the clinic.

Outcomes and Results: The primary outcome was the proportion of patients who had recurrence of stroke within 90 days of first presentation. The authors followed up all patients with TIA or minor stroke in the geographical area, whether or not they were referred to the specialist clinic. Among all out-patient managed patients, the rate of recurrence decreased from 10.2% in phase 1 to 2.0% in phase 2 (relative risk reduction 80.4%, absolute reduction 8.2%, NNT=12 , P<0.0001).

Sponsorship: EXPRESS is part of the OXVASC project, which is funded by the UK Medical Research Council, the Dunhill Medical Trust, the Stroke Association, the BUPA Foundation, the National Institute for Health Research, and the Thames Valley Primary Care Research Partnership.