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Research Article| Volume 367, P18-21, August 15, 2016

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

      Highlights

      • Stroke is associated with microembolic signal (MES).
      • 2 MES size can be estimated by monitoring the intensity via transcranial doppler.
      • Clopidogrel and aspirin more effectively reduce MES intensity than aspirin alone.
      • MES intensity is an important parameter in TCD monitoring.

      Abstract

      Background

      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.

      Methods

      We recruited 100 patients who experienced acute ischemic stroke or transient ischemic attack (TIA) within 7 days 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 7 days. MES monitoring was performed on days 2 and 7.

      Results

      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 (012) dB on day 7 (P = 0.000). In the monotherapy group, the MES intensity was 9.00 (020) 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.

      Conclusions

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

      Keywords

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      References

        • Rothwell P.M.
        • Buchan A.
        • Johnston S.C.
        Recent advances in management of transient ischaemic attacks and minor ischaemic strokes.
        Lancet Neurol. 2006; 5: 323-331
        • Markus H.S.
        • Droste D.W.
        • Kaps M.
        • Larrue V.
        • Lees K.R.
        • Siebler M.
        • et al.
        Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using doppler embolic signal detection: the clopidogrel and aspirin for reduction of emboli in symptomatic carotid stenosis (caress) trial.
        Circulation. 2005; 111: 2233-2240
        • Kennedy J.
        • Hill M.D.
        • Ryckborst K.J.
        • Eliasziw M.
        • Demchuk A.M.
        • Buchan A.M.
        Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (faster): a randomised controlled pilot trial.
        Lancet Neurol. 2007; 6: 961-969
        • Chimowitz M.I.
        • Lynn M.J.
        • Howlett-Smith H.
        • Stern B.J.
        • Hertzberg V.S.
        • Frankel M.R.
        • et al.
        Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis.
        N. Engl. J. Med. 2005; 352: 1305-1316
        • Wong K.S.
        • Chen C.
        • Ng P.W.
        • Tsoi T.H.
        • Li H.L.
        • Fong W.C.
        • et al.
        Low-molecular-weight heparin compared with aspirin for the treatment of acute ischaemic stroke in asian patients with large artery occlusive disease: a randomised study.
        Lancet Neurol. 2007; 6: 407-413
        • Kwon S.U.
        • Cho Y.J.
        • Koo J.S.
        • Bae H.J.
        • Lee Y.S.
        • Hong K.S.
        • et al.
        Cilostazol prevents the progression of the symptomatic intracranial arterial stenosis: the multicenter double-blind placebo-controlled trial of cilostazol in symptomatic intracranial arterial stenosis.
        Stroke. 2005; 36: 782-786
        • Spence J.D.
        • Tamayo A.
        • Lownie S.P.
        • Ng W.P.
        • Ferguson G.G.
        Absence of microemboli on transcranial doppler identifies low-risk patients with asymptomatic carotid stenosis.
        Stroke. 2005; 36: 2373-2378
        • Mackinnon A.D.
        • Aaslid R.
        • Markus H.S.
        Ambulatory transcranial doppler cerebral embolic signal detection in symptomatic and asymptomatic carotid stenosis.
        Stroke. 2005; 36: 1726-1730
        • Abbott A.L.
        • Chambers B.R.
        • Stork J.L.
        • Levi C.R.
        • Bladin C.F.
        • Donnan G.A.
        Embolic signals and prediction of ipsilateral stroke or transient ischemic attack in asymptomatic carotid stenosis: a multicenter prospective cohort study.
        Stroke. 2005; 36: 1128-1133
        • Markus H.S.
        • MacKinnon A.
        Asymptomatic embolization detected by Doppler ultrasound predicts stroke risk in symptomatic carotid artery stenosis.
        Stroke. 2005; 36: 971-975
        • Gao S.
        • Wong K.S.
        • Hansberg T.
        • Lam W.W.
        • Droste D.W.
        • Ringelstein E.B.
        Microembolic signal predicts recurrent cerebral ischemic events in acute stroke patients with middle cerebral artery stenosis.
        Stroke. 2004; 35: 2832-2836
        • Wong K.S.
        • Chen C.
        • Fu J.
        • Chang H.M.
        • Suwanwela N.C.
        • Huang Y.N.
        • et al.
        Clopidogrel plus aspirin versus aspirin alone for reducing embolisation in patients with acute symptomatic cerebral or carotid artery stenosis (clair study): a randomised, open-label, blinded-endpoint trial.
        Lancet Neurol. 2010; 9: 489-497
        • Jovanovic Z.B.
        • Pavlovic A.M.
        • Zidverc-Trajkovic J.J.
        • Mijajlovic M.D.
        • Radojicic A.P.
        • Covickovic-Sternic N.M.
        Transcranial doppler test for evaluation of cerebral artery embolism–microemboli detection.
        Srp. Arh. Celok. Lek. 2008; 136: 302-306
        • Almekhlafi M.A.
        • Demchuk A.M.
        • Mishra S.
        • Bal S.
        • Menon B.K.
        • Wiebe S.
        • et al.
        Malignant emboli on transcranial doppler during carotid stenting predict postprocedure diffusion-weighted imaging lesions.
        Stroke. 2013; 44: 1317-1322
        • Martin M.J.
        • Chung E.M.
        • Ramnarine K.V.
        • Goodall A.H.
        • Naylor A.R.
        • Evans D.H.
        Thrombus size and doppler embolic signal intensity.
        Cerebrovasc. Dis. 2009; 28: 397-405
        • Russell D.
        • Madden K.P.
        • Clark W.M.
        • Sandset P.M.
        • Zivin J.A.
        Detection of arterial emboli using doppler ultrasound in rabbits.
        Stroke. 1991; 22: 253-258
        • Kiri V.A.
        • MacKenzie G.
        How real is intention-to-treat (itt) analysis in non-interventional post authorization safety studies? We can do better.
        Curr Drug Saf. 2009; 4: 137-142
        • Diener H.C.
        • Bogousslavsky J.
        • Brass L.M.
        • Cimminiello C.
        • Csiba L.
        • Kaste M.
        • et al.
        Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (match): randomised, double-blind, placebo-controlled trial.
        Lancet. 2004; 364: 331-337
        • Telman G.
        • Sprecher E.
        • Kouperberg E.
        Potential relevance of low-intensity microembolic signals by tcd monitoring.
        Neurol. Sci. 2011; 32: 107-111