Elsevier

The Lancet Neurology

Volume 6, Issue 11, November 2007, Pages 961-969
The Lancet Neurology

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Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial

https://doi.org/10.1016/S1474-4422(07)70250-8Get rights and content

Summary

Background

Patients with transient ischaemic attack (TIA) or minor stroke are at high immediate risk of stroke. The optimum early treatment options for these patients are not known.

Methods

Within 24 h of symptom onset, we randomly assigned, in a factorial design, 392 patients with TIA or minor stroke to clopidogrel (300 mg loading dose then 75 mg daily; 198 patients) or placebo (194 patients), and simvastatin (40 mg daily; 199 patients) or placebo (193 patients). All patients were also given aspirin and were followed for 90 days. Descriptive analyses were done by intention to treat. The primary outcome was total stroke (ischaemic and haemorrhagic) within 90 days. Safety outcomes included haemorrhage related to clopidogrel and myositis related to simvastatin. This study is registered as an International Standard Randomised Controlled Trial (number 35624812) and with ClinicalTrials.gov (NCT00109382).

Findings

The median time to stroke outcome was 1 day (range 0–62 days). The trial was stopped early due to a failure to recruit patients at the prespecified minimum enrolment rate because of increased use of statins. 14 (7·1%) patients on clopidogrel had a stroke within 90 days compared with 21 (10·8%) patients on placebo (risk ratio 0·7 [95% CI 0·3–1·2]; absolute risk reduction −3·8% [95% CI −9·4 to 1·9]; p=0·19). 21 (10·6%) patients on simvastatin had a stroke within 90 days compared with 14 (7·3%) patients on placebo (risk ratio 1·3 [0·7–2·4]; absolute risk increase 3·3% [−2·3 to 8·9]; p=0·25). The interaction between clopidogrel and simvastatin was not significant (p=0·64). Two patients on clopidogrel had intracranial haemorrhage compared with none on placebo (absolute risk increase 1·0% [−0·4 to 2·4]; p=0·5). There was no difference between groups for the simvastatin safety outcomes.

Interpretation

Immediately after TIA or minor stroke, patients are at high risk of stroke, which might be reduced by using clopidogrel in addition to aspirin. The haemorrhagic risks of the combination of aspirin and clopidogrel do not seem to offset this potential benefit. We were unable to provide evidence of benefit of simvastatin in this setting. This aggressive prevention approach merits further study.

Introduction

Time is crucial to the treatment of patients with cerebrovascular disease. Systems of care have been forced to become more responsive with the evidence that selected patients who receive thrombolysis with alteplase (recombinant tissue plasminogen activator, rt-PA) within 3 h of the onset of ischaemic stroke have an increased chance of excellent functional outcome.1 However, the introduction of alteplase has also indicated those populations of patients for whom alternative treatment strategies need to be found, analogous to cardiology in which different treatments have evolved for ST elevation and non-ST elevation myocardial infarction.2, 3

Patients have an unstable clinical course in the immediate aftermath of transient ischaemic attack (TIA) and minor stroke and have a high risk of recurrent stroke, most of which accrues in the initial 48 h after symptom onset.4, 5, 6, 7 Patients who substantially recover from their initial deficit are at the greatest risk of deterioration.8, 9 Alteplase is contraindicated in patients who recover, particularly those either rapidly improving or with a mild deficit,10 but those patients excluded from alteplase treatment for these reasons are at a high subsequent risk of death or dependence at hospital discharge.11 Secondary stroke prevention trials have either not focused on this period of immediate high risk (eg, MATCH [within 3 months of symptom onset] and ESPRIT [within 6 months] trials, trial acronyms defined in panel),12, 13 or actively excluded such patients from randomisation (eg, SPARCL [patients not eligible for randomisation within 1 month of symptoms] and CAPRIE [not within 1 week of symptoms] trials).14, 15 Only the International Stroke Trial and Chinese Acute Stroke Trial have previously concentrated on enrolling patients with acute stroke within 48 h to an antiplatelet trial, both of which showed a reduction in the risk of recurrent stroke with the use of aspirin.16, 17, 18

The Fast Assessment of Stroke and TIA to prevent Early Recurrence (FASTER) trial was designed to assess, in a factorial design, whether clopidogrel and simvastatin, if started within 24 h of symptom onset and continued for 90 days, would reduce the risk of stroke after TIA or minor stroke.

Section snippets

Participants

Between May, 2003, and December, 2006, patients aged 40 years or older with a minor stroke, as defined by a US National Institutes of Health stroke scale (NIHSS) score of 3 or less at the time of randomisation, or TIA within 24 h of onset were eligible for enrolment. In addition, weakness or speech disturbance, dysarthria or dysphasia, had to be part of the symptom complex for greater than 5 min for patients to be eligible. The institutional review boards of each of the participating hospitals

Results

3101 patients with suspected TIA or ischaemic stroke presenting within 24 h of symptom onset were screened at 18 centres for study enrolment, among which 288 (9·3% of the screened population) were excluded for failure to meet an inclusion criterion and 2417 (77·9%) were excluded for meeting an exclusion criterion (table 1). 396 (12·8%) patients took the trial medication and were thus enrolled into the trial. However, four patients withdrew consent from involvement in the trial within 24 h of

Discussion

The FASTER trial underscores the high risk of stroke in the immediate aftermath of symptom onset in patients with acute ischaemic cerebrovascular events, whose symptoms have either completely recovered or are too mild, precluding them from treatment with alteplase. Early aggressive antiplatelet therapy may be associated with a reduction in these events, although at the cost of slightly increased haemorrhagic complications. Early simvastatin use does not seem to have a similar effect, and may

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