Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis - CARESS


The goal of the trial was to evaluate dual antiplatelet therapy with aspirin plus clopidogrel compared with aspirin alone among patients with recently symptomatic ≥50% carotid stenosis and asymptomatic microembolic signals.

Study Design

Study Design:

Patients Screened: 230
Patients Enrolled: 107
Mean Follow Up: 7 days
Mean Patient Age: Mean age 64 years
Female: 31

Patient Populations:

Age >18 years; ≥50% carotid stenosis; and had experienced ipsilateral carotid territory TIA or stroke within the last 3 months.


Clinical and/or brain CT findings compatible with hemorrhagic transformation; recent strokes with focal hypodensity in> 33% of corresponding middle cerebral artery territory on initial CT scan or National Institutes of Health Stroke Scale score >22; carotid endarterectomy scheduled within the next 2 weeks; acoustic window that did not allow TCD recordings; atrial fibrillation or other major cardiac source of embolism; thrombolysis within the last 2 weeks; anticoagulation within the last 3 days; administration of antiplatelet agents other than aspirin within the last 3 weeks; history of clinically significant or persistent thrombocytopenia or of bleeding diathesis or coagulopathy; history of clinically significant or persistent neutropenia; history of drug allergy to thienopyridine derivatives and/or aspirin.

Primary Endpoints:

Proportion of patients who were MES positive at day 7

Secondary Endpoints:

Proportion of patients who were MES positive on day 2, the rate of embolization (number of MES per hour) on both days 2 and 7, and their percent change from baseline.

Drug/Procedures Used:

Patients underwent transcranial Doppler ultrasound prior to enrollment in the trial to ensure the presence of asymptomatic microembolic signals (MES), a risk factor for future stroke or transient ischemic attack (TIA). Once the presence of asymptomatic MES was confirmed, patients were randomized to clopidogrel (300 mg loading dose and 75 mg per day thereafter) and aspirin (75 mg per day) (n=51) or aspirin alone (75 mg per day) (n=56). Follow-up transcranial Doppler ultrasound was performed on day 2 and day 7.

Principal Findings:

Of the 230 patients who underwent a screening transcranial Doppler ultrasound, 47.8% (n=110) had MES detected and 107 were enrolled in the trial. The qualifying event was TIA in 61.7% of patients and stroke in 38.3% of patients. The mean carotid stenosis was 84.3% in the dual therapy group and 80.2% in the monotherapy group (p=0.082).

The primary endpoint of MES positive at day 7 was significantly lower in the dual therapy group (43.8% vs 72.7%, relative risk reduction [RRR] 39.8%, p=0.005). Evidence of benefit for MES reduction was beginning to be observed at day 2 (56.0% vs 74.1%, p=0.065). Likewise, the frequency of MES per hour was lower in the dual therapy group at both day 2 (mean 3.3 vs 9.5, p<0.001) and day 7 (mean 1.8 vs 5.9, p=0.001). Results were similar in the per protocol analysis.

Recurrent ipsilateral ischemic stroke during the 1 week follow-up occurred in 4 patients in the monotherapy group and none in the dual therapy group. The rate of TIA or ischemic stroke was 9.8% in the dual therapy group and 21.4% in the monotherapy group (p=NS). Bleeding events did not differ significantly in the dual therapy group vs monotherapy group (3.9% vs 1.8%).

In a platelet substudy (n=71), the mean maximum intensity of platelet aggregation at day 7 higher in the monotherapy group (106.7% of baseline) compared with the dual-therapy group (70.9% of baseline) (p=0.0001).


Among patients with recently symptomatic ≥50% carotid stenosis and asymptomatic microembolic signals, use of dual therapy with clopidogrel plus aspirin was associated with a reduction in both the proportion and number of MES at day 7 compared with aspirin monotherapy. The MATCH trial showed no additional benefit of clopidogrel plus aspirin over clopidogrel alone. However, there are several differences in the trial, including a different control arm (clopidogrel monotherapy) and enrollment of patients several weeks after the index event, which could include any ischemic stroke.


Markus HS, et al. Dual Antiplatelet Therapy with Clopidogrel and Aspirin in Symptomatic Carotid Stenosis Evaluated Using Doppler Embolic Signal Detection. Circulation. 2005;111:2233-2240.

Keywords: Stroke, Ischemic Attack, Transient, Platelet Aggregation Inhibitors, Cerebrovascular Disorders, Platelet Aggregation, Risk Factors, Ticlopidine, Carotid Stenosis, Hemorrhage

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