Clopidogrel resistance in stroke patients (The CRISP Trial)
- Journal of Neurology & Stroke
E Qazi,1 Syed AH Zaidi,1 Olukolade O Owojori,2 LJ Bonnett,3 PR Fitzsimmons,1 N Sharma,1 B Menezes,4 J Thachil,3 W Greenhalf,4 M Oates,3 P Lopez,1 G Fletcher,1 P Cox,1 F Hussain,1 J Lloyd,3 A Manoj1
- 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 aprospective 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.
clopidogrel resistance, ischaemic stroke, vasodilator-stimulated phosphoprotein