Dual Antiplatelet Therapy With Clopidogrel and Aspirin in Symptomatic Carotid Stenosis Evaluated Using Doppler Embolic Signal Detection
Top Cited Papers
- 3 May 2005
- journal article
- clinical trial
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 111 (17), 2233-2240
- https://doi.org/10.1161/01.cir.0000163561.90680.1c
Abstract
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.Keywords
This publication has 23 references indexed in Scilit:
- 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 trialThe Lancet, 2004
- Population based study of early risk of stroke after transient ischaemic attack or minor stroke: implications for public education and organisation of servicesBMJ, 2004
- Cerebral Microembolism Is Blocked by Tirofiban, a Selective Nonpeptide Platelet Glycoprotein IIb/IIIa Receptor AntagonistCirculation, 2003
- Cessation of embolic signals after antithrombotic prevention is related to reduced risk of recurrent arterioembolic transient ischaemic attack and strokeJournal of Neurology, Neurosurgery & Psychiatry, 2002
- Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patientsBMJ, 2002
- Doppler microembolic signals predict ischemic recurrences in symptomaticcarotid stenosisActa Neurologica Scandinavica, 2000
- Prevalence and frequency of microembolic signals in 105 patients with extracranial carotid artery occlusive diseaseJournal of Neurology, Neurosurgery & Psychiatry, 1999
- A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE)The Lancet, 1996
- Tissue Plasminogen Activator for Acute Ischemic StrokeNew England Journal of Medicine, 1995
- Quantification of Atheromatous Stenosis in the Extracranial Internal Carotid ArteryCerebrovascular Diseases, 1995