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

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.