Article Text
Abstract
Background Antiplatelet agents reduce recurrence after cerebral ischaemia but are not effective in all patients, in part because of treatment resistance. The primary aim was to assess the proportion of patients who are insensitive to clopidogrel. The secondary aim was to assess the association between insensitivity to clopidogrel and recurrent cerebrovascular events.
Methods Following written informed consent, independent patients with a recent non-cardioembolic ischaemic stroke or transient ischaemic attack, and taking clopidogrel, were enrolled. Platelet function was assessed with remote measurement of surface expression of P-selectin (CD62P) using commercial kits sensitive to aspirin or clopidogrel. Participants’ general practitioners provided details on recurrent vascular events at least 90 days later. Data are mean (SD) and median [IQR]. Resistance was defined as: aspirin median fluorescence (MF) >500 units, clopidogrel MF >860 units. Non-parametric descriptors and tests were used.
Results 63 patients were recruited: mean age 64 (13.7) years, women 47%. At baseline, 59 (95%) patients were taking clopidogrel alone with 3 (5%) on combined clopidogrel and aspirin. Assessment of platelet surface P-selectin revealed: aspirin test 528 [317, 834], >500 54.8%; clopidogrel test 429 [303, 656], >860 11.3%. No participants on aspirin and clopidogrel showed aspirin resistance. Thirteen (20.6%) patients had a recurrent cerebrovascular event; those with an ischaemic stroke had a non-significantly higher baseline P-selectin using the clopidogrel test as compared with those with no recurrence: 626 [380, 801] versus 406 [265, 609], p=0.08.
Conclusions Remote measurement of platelet function assessed using the platelet surface expression of P-selectin is feasible. 11% of patients taking clopidogrel showed resistance. No significant associations were noted between clopidogrel resistance and recurrent ischaemic events.
- stroke
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Footnotes
Twitter @JPAppleton
Contributors JPA analysed and interpreted the data and wrote the manuscript. JPA and CR were involved in data collection. ND and JM performed the laboratory analysis of the blood samples. NS, SH and PMB critically appraised the manuscript. PMB is responsible for study design, delivery and is study guarantor.
Funding The study was funded by Platelet Solutions (Nottingham UK) and Innovate UK SMART award.
Competing interests JA was funded in part by a National Institute of Health Research (NIHR) Health Technology Assessment grant for the TARDIS trial. JM and SH are inventors of the P-selectin assay and own stock in Platelet Solutions Ltd (PSL). ND is an employee and owns stock in PSL. PMB is Stroke Association Professor of Stroke Medicine and is a National Institute of Health Research Senior Investigator; he owns stock in PSL and has consulted previously for Sanofi and Boehringer Ingelheim.
Patient consent for publication Not required.
Ethics approval East Midlands UK ethics committee (06/Q2403/137; version 4.1, 12.10.2015).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data pertaining to this paper are available from the corresponding author upon reasonable request.