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J Neurol Sci. 2016 Aug 15;367:18-21. doi: 10.1016/j.jns.2016.05.042. Epub 2016 May 21.

The curative effect comparison of two kinds of therapeutic regimens on decreasing the relative intensity of microembolic signal in CLAIR trial.

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Department of Neurology, Jing'an District Central Hospital of Shanghai, Shanghai, China. Electronic address:
Department of Neurology, Huashan Hospital affiliated to Fudan University, Shanghai, China. Electronic address:
Department of Pharmacology, National University of Singapore, Singapore. Electronic address:
Department of Clinical Neuroscience, St George's, University of London, London, UK. Electronic address:
Department of Neurology, Peking University First Hospital, Beijing, China. Electronic address:
Department of Neurology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China. Electronic address:
Ramathibodi Hospital, Bangkok, Thailand. Electronic address:
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China. Electronic address:
Department of Neurology, Huashan Hospital affiliated to Fudan University, Shanghai, China; Department of Neurology, Pudong hospital, Shanghai, China. Electronic address:



Microembolic signals (MESs) are direct markers of unstable large artery atherosclerotic plaques. In a previous study, we found that the number of MESs is associated with stroke recurrence and that clopidogrel plus aspirin more effectively reduce the number of MESs than does aspirin alone. Stroke recurrence is associated with not only the number of MESs but also the size of the MES, which can theoretically be estimated by monitoring the MES intensity via transcranial doppler (TCD). Thus, we compared the effects of clopidogrel and aspirin with aspirin alone on MES intensity using TCD.


We recruited 100 patients who experienced acute ischemic stroke or transient ischemic attack (TIA) within 7days of symptom onset. All patients also had large artery stenosis in the cerebral or carotid arteries and the presence of MES as revealed by TCD. The patients were randomized to receive either aspirin or clopidogrel and aspirin for 7days. MES monitoring was performed on days 2 and 7.


Intent-to-treat (ITT) analysis (46 patients in the dual therapy group, 52 patients in the monotherapy group) and per-protocol (PP) analysis (25 patients in the dual therapy group, 31 patients in the monotherapy group) were performed on 98 patients. The primary finding was that the MES intensity was dramatically reduced in the dual therapy group. ITT analysis of the dual therapy group revealed that the MES intensity was 8.04 (0-16) dB before treatment, 0.00 (0-17) dB on day 2, and 0.00 (0-12) dB on day 7 (P=0.000). In the monotherapy group, the MES intensity was 9.00 (0-20) dB before treatment, 8.25 (0-17) dB on day 2, and 7.0 (0-18) dB on day 7 (P=0.577). PP analysis revealed similar results. No severe hemorrhagic complications were detected. The two patients in this study who experienced stroke recurrence were in the monotherapy group.


Clopidogrel and aspirin more effectively decrease the MES intensity than aspirin alone in patients with large artery stenotic minor stroke or TIA.


Aspirin; Clopidogrel; Large artery stenosis; Microembolic signals; The relative intensity; Transcranial doppler

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