Abstract T P344: Clopidogrel Resistance in Stroke Patients (The CRISP Trial)

Abstract

Background: Clopidogrel is a thienopyridine with ADP antagonising effects that is widely used in the secondary prevention of ischemic strokes and transient ischemic attacks (TIAs). Despite this some patients will go on to have recurrent strokes or TIAs. Cardiology trials have identified patients with clopidogrel resistance, defined as a vasodilator-stimulated phosphoprotein (VASP) index of >50% after at least 7 days of clopidogrel treatment. This was associated with recurrent cardiac events. The VASP-index measures phosphorylation of VASP in the resting state and activated states using flow cytometry techniques. As phosphorylation of VASP is dependent upon activation of the platelet P2Y12 receptor that is targeted by clopidogrel the difference in phosphorylation between the two states provides an indirect measure of platelet inhibition. Previous trials have shown a prevalence of clopidogrel resistance in stroke patients of between 8 and 18%, but no study to date has shown whether this is associated with significantly more recurrent cerebrovascular events. We are testing the hypothesis that amongst patients treated with clopidogrel for secondary prevention of cerebrovascular disease, those with resistance are more likely to have recurrent Strokes or TIAs. Should this hypothesis be confirmed, then further research would be needed to identify treatment strategies that may minimise this risk. Design A prospective cohort study recruiting 120 patients from the acute stroke unit at the Royal Liverpool hospital with a diagnosis of stroke or TIA that will be commenced on clopidogrel therapy and expected to continue it for at least one year. We will compare outcomes between those found to be 'clopidogrel responders' and 'clopidogrel resistant'. A sample size of 120 patients was chosen based on the concept of 'reproducibility probability', taking into account the number of patients needed for similar studies in cardiology patients, the prevalence of 'clopidogrel resistance' amongst stroke patients and the potential for patients to later be excluded. Outcome Recurrent cerebrovascular event within 6 months of entering trial. Trial Status Recruitment ongoing.