Published online before print April 25, 2005, doi: 10.1161/01.CIR.0000163561.90680.1C
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(Circulation. 2005;111:2233-2240.)
© 2005 American Heart Association, Inc.
Stroke |
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
From the Department of Clinical Neuroscience, St George’s Hospital Medical School, London, UK (H.S.M.); Service de Neurologie, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg (D.W.D.); Klinik und Poliklinik für Neurologie, Westfälische Wilhelms Universität, Münster, Germany (D.W.D., E.B.R.); Department of Neurology, Justus-Liebig Universitaet, Giessen, Germany (M.K.); Department of Neurology, University of Toulouse, Toulouse, France (V.L.); Acute Stroke Unit and Cerebrovascular Clinic, University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary and University of Glasgow, Glasgow, UK (K.R.L.); and Klinik für Neurologie, Heinrich-Heine Universität, Düsseldorf, Germany (M.S.).
Correspondence to Dr Hugh Markus, Department of Clinical Neuroscience, St George’s Hospital Medical School, Cranmer Terrace, London, SW17 ORE, UK. E-mail h.markus{at}sghms.ac.uk
Received August 10, 2004; revision received January 13, 2005; accepted January 19, 2005.
Background— Evidence for efficacy of dual antiplatelet therapy in stroke is limited. Symptomatic carotid stenosis patients are at high risk of early recurrent stroke. In this group, asymptomatic microembolic signals (MES), detected by transcranial Doppler ultrasound (TCD), are markers of future stroke and transient ischemic attack (TIA) risk. They offer a surrogate marker to evaluate antiplatelet therapy, but no multicenter study has evaluated the feasibility of this approach.
Methods and Results— Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) is a randomized, double-blind study in subjects with recently symptomatic 
50% carotid stenosis. Patients were screened with TCD, and if MES were detected, they were randomized to clopidogrel and aspirin or aspirin monotherapy. Repeated TCD recordings were made on days 2 and 7. MES were detected in 110 of 230 patients by online analysis at baseline, of whom 107 were randomized. Intention-to-treat analysis revealed a significant reduction in the primary end point: 43.8% of dual-therapy patients were MES positive on day 7, as compared with 72.7% of monotherapy patients (relative risk reduction 39.8%; 95% CI, 13.8 to 58.0; P=0.0046). The secondary end point of MES frequency per hour was reduced (compared with baseline) by 61.4% (95% CI, 31.6 to 78.2; P=0.0013) in the dual-therapy group at day 7 and by 61.6% (95% CI, 34.9 to 77.4; P=0.0005) on day 2. There were 4 recurrent strokes and 7 TIAs in the monotherapy group versus no stroke and 4 TIAs in the dual-therapy group that were treatment emergent and ipsilateral to the qualifying carotid stenosis; 2 additional ipsilateral TIAs occurred before treatment started. MES frequency was greater in the 17 patients with recurrent ipsilateral events compared with the 90 without (mean±SD: 24.4±27.7 versus 8.9±11.5 per hour; P=0.0003).
Conclusions— In patients with recently symptomatic carotid stenosis, combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing asymptomatic embolization. Doppler MES detection is a feasible method to evaluate the efficacy of antiplatelet therapy in multicenter studies.
Key Words: trials • embolism • stroke • ultrasonics • carotid arteries
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