Elsevier

The Lancet

Volume 370, Issue 9596, 20–26 October 2007, Pages 1432-1442
The Lancet

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Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison

https://doi.org/10.1016/S0140-6736(07)61448-2Get rights and content

Summary

Background

The risk of recurrent stroke is up to 10% in the week after a transient ischaemic attack (TIA) or minor stroke. Modelling studies suggest that urgent use of existing preventive treatments could reduce the risk by 80–90%, but in the absence of evidence many health-care systems make little provision. Our aim was to determine the effect of more rapid treatment after TIA and minor stroke in patients who are not admitted direct to hospital.

Methods

We did a prospective before (phase 1: April 1, 2002, to Sept 30, 2004) versus after (phase 2: Oct 1, 2004, to March 31, 2007) study of the effect on process of care and outcome of more urgent assessment and immediate treatment in clinic, rather than subsequent initiation in primary care, in all patients with TIA or minor stroke not admitted direct to hospital. The study was nested within a rigorous population-based incidence study of all TIA and stroke (Oxford Vascular Study; OXVASC), such that case ascertainment, investigation, and follow-up were complete and identical in both periods. The primary outcome was the risk of stroke within 90 days of first seeking medical attention, with independent blinded (to study period) audit of all events.

Findings

Of the 1278 patients in OXVASC who presented with TIA or stroke (634 in phase 1 and 644 in phase 2), 607 were referred or presented direct to hospital, 620 were referred for outpatient assessment, and 51 were not referred to secondary care. 95% (n=591) of all outpatient referrals were to the study clinic. Baseline characteristics and delays in seeking medical attention were similar in both periods, but median delay to assessment in the study clinic fell from 3 (IQR 2–5) days in phase 1 to less than 1 (0–3) day in phase 2 (p<0·0001), and median delay to first prescription of treatment fell from 20 (8–53) days to 1 (0–3) day (p<0·0001). The 90-day risk of recurrent stroke in the patients referred to the study clinic was 10·3% (32/310 patients) in phase 1 and 2·1% (6/281 patients) in phase 2 (adjusted hazard ratio 0·20, 95% CI 0·08–0·49; p=0·0001); there was no significant change in risk in patients treated elsewhere. The reduction in risk was independent of age and sex, and early treatment did not increase the risk of intracerebral haemorrhage or other bleeding.

Interpretation

Early initiation of existing treatments after TIA or minor stroke was associated with an 80% reduction in the risk of early recurrent stroke. Further follow-up is required to determine long-term outcome, but these results have immediate implications for service provision and public education about TIA and minor stroke.

Introduction

The risk of recurrent stroke in the week after a transient ischaemic attack (TIA) or minor stroke is up to 10%.1, 2, 3 About 150 000 suspected TIAs and minor strokes are referred to secondary care for assessment and investigation in England alone each year,4 and rates are similar in the USA.5 These warning events provide a short window of opportunity for prevention,6 but there is considerable variation in service provision, ranging from emergency inpatient care to non-urgent outpatient clinic assessment,7, 8 with little consensus about the most cost-effective strategy.9, 10 In the UK, it is recommended that patients are seen in specialist outpatient clinics,11 but many hospitals offer only a weekly clinic and about half of all patients in the UK wait more than 14 days to be seen, and have even longer delays to investigation, and treatment.12

Several treatments are effective in preventing stroke in the long term after a TIA or minor ischaemic stroke, including aspirin,13 other antiplatelet agents,14, 15, 16 blood-pressure-lowering drugs,17 statins,18 anticoagulation for atrial fibrillation,19 and endarterectomy for 50% or greater symptomatic carotid stenosis.20, 21 Assuming that these effects are independent, use of all of these interventions in appropriate patients would be predicted to reduce the long-term group risk of recurrent stroke by 80–90%.22 Moreover, evidence from trials of treatment in acute stroke and acute coronary syndromes suggests that the relative benefits of several of these interventions are, if anything, likely to be even greater in the acute phase.23, 24, 25, 26, 27, 28 However, there are no large randomised trials of these, or any other interventions, in the acute phase after TIA and minor ischaemic stroke; this lack of evidence has undoubtedly contributed to the variation in service provision.

In 2002, in light of increasing evidence of the high early risk of stroke after TIA,1, 29 and of high rates of stroke before assessment in an audit of referrals to our weekly TIA clinic,30 we aimed to determine the effect of more rapid treatment after TIA and minor stroke in patients who are not admitted direct to hospital. Given the predicted benefits of early treatment, and emerging evidence of substantial benefits of early endarterectomy for symptomatic carotid stenosis,31 we considered randomisation to early versus delayed assessment and treatment to be unethical and unfeasible. We therefore instigated a rigorous observational study of the phased introduction of early assessment and treatment (Early use of EXisting PREventive Strategies for Stroke; EXPRESS), nested within a population-based study of all incident and recurrent TIA and stroke in Oxfordshire, UK (Oxford Vascular Study; OXVASC).32, 33

Section snippets

Patients

The methods of OXVASC and details of the study population have been reported previously.32, 33 Briefly, the study population consisted of all 91 000 individuals, irrespective of age, registered with 63 primary-care physicians in nine primary-care practices in Oxfordshire, UK. In the UK, almost all individuals register with a primary-care practice, which holds a lifelong medical record. OXVASC was approved by our local research ethics committee and began on April 1, 2002, after a 3-month pilot

Results

Table 1 shows the number of patients seeking medical attention after a first event, stratified by place of presentation and by type of first event (probable or definite TIA or stroke). 51 patients sought medical attention after an event in both phases. 40 OXVASC patients presenting with subarachnoid haemorrhage and ten patients with stroke who died in the community before reaching medical attention were excluded; 23 patients who first sought medical attention outside Oxfordshire were included.

Discussion

Our data indicate that urgent assessment and early initiation of a combination of existing preventive treatments can reduce the risk of early recurrent stroke after TIA or minor stroke by about 80%, and reduce the total number of all early recurrent strokes in the whole population by over half. Extrapolated across the UK population, this equates to the prevention of nearly 10 000 strokes per year.

Our study was not a randomised comparison, but it has produced a reliable estimate of the effect of

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