Clopidogrel resistance in stroke patients (The CRISP Trial)

Abstract

Objective: To investigate the incidence of clopidogrel resistance in patients with acute ischaemic stroke and to evaluate whether there is an association between clopidogrel resistance and the occurrence of a further cerebrovascular ischaemic event using the vasodilator-stimulated phosphoprotein (VASP) index as a marker of clopidogrel resistance. Methods: It is a prospective cohort study that recruited 120 patients from the acute stroke unit at the Royal Liverpool University Hospital. All patients with confirmed acute ischaemic stroke had clopidogrel 75mg/day at discharge or after 14 days of acute stroke if deemed by the direct clinical team to be the most appropriate treatment. After at least 7 days of clopidogrel 75mg/day, all those patients fulfilling inclusion/exclusion criteria had phosphorylation of vasodilator-stimulated phosphoprotein (VASP) measured. If VASP measured ≥50% after ≥7 days of clopidogrel maintenance, these patients were deemed as ‘clopidogrel resistant’, while those with VASP <50% were deemed as ‘clopidogrel responder’. Statistical analysis was by univariable analysis which considered the association of each variable – diagnosis, age, duration of clopidogrel, VASP, days to VASP, and number of comorbidities – with the outcome. Risk of second stroke after a first at 6, 12 and 24 months was estimated using logistic regression. Results: No variables were significantly associated with risk of stroke at 6 months with clopidogrel resistance having no significant effect on likelihood of a further stroke compared to the no clopiodgrel resistance cohort (p value= 0.39). Results were similar at 12 months follow up. However, at 24 months VASP index was significantly associated with risk of a further stroke; each one unit increase in VASP was associated with a 3% increase in risk of stroke at 24 months (p value = 0.05, CI Interval of 1.00- 1.06). Conclusion: No variables were significantly associated with risk of further stroke at 6 months and 12 months after a first stroke. However, VASP was significantly associated with risk of further stroke at 24 months with increasing VASP leading to a higher risk of further stroke.