Residual Platelet Reactivity in Patients on Antiplatelet Therapy After Carotid Angioplasty With Stenting

Study Overview
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Brief Summary
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A carotid stenosis is treated with invasive procedures of revascularization when the lumen is reduced by more than 70% or when the lumen is reduced by more than 50% in patients who have had symptoms attributable to the affected carotid district in last the 6 months. Two options for the treatment of patients with carotid stenosis exist currently: the traditional surgical intervention of removal of the plaque by carotid endoarterectomy (CEA)and percutaneous transluminal carotid angioplasty with a balloon associated to the positioning of a stent through a catheter brought directly in the carotid artery (CAS). The main complication of both the procedures is early thrombosis, a phenomenon in which platelets play a central role. The importance of an effective inhibition of platelet activation in these patients has been widely demonstrated. Clinical studies in patients undergoing PTCA have demonstrated that the optimal treatment for the prevention of stent thrombosis is a dual antiplatelet regimen with aspirin plus clopidogrel, as compared with the single drugs. Given that no specific clinical trial has assessed the best antiplatelet therapeutic regimen in CAS with stenting, by extension from these findings in ischemic heart disease CAS patients are treated with aspirin plus clopidogrel. Several studies have demonstrated that an elevated residual platelet reactivity despite treatment with clopidogrel is associated to an increased risk of major adverse cardiovascular events (MACE) after stenting for coronary disease. No data are instead available on the possible predictive value of residual platelet reactivity for the incidence of ischemic cardiovascular events in patients with atherosclerotic carotid disease undergoing CAS with stenting. Aim of the study will be to assess the predictive value of residual platelet reactivity, as measured by different laboratory tests in patients undergoing CAS with stenting and treated with aspirin plus clopidogrel, for the incidence of cardiovascular complications (major adverse ischemic events).

Detailed Description
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STUDY DESIGN The study will enroll 110 patients undergoing stenting for critical carotid stenosis, either symptomatic (previous events of cerebral ischemia) or asymptomatic, undergoing CAS. All patients undergoing CAS in our Center and that fit the predefined Criteria will be enrolled in the study. Dual-antiplatelet treatment with aspirin and clopidogrel will be administered to all patients with the same modalities in use for coronary heart disease patients undergoing PTCA. Implanted stents after CAS will be in all patients bare metal stents (BMS) and therefore, by analogy with the studies in ACS, the duration of dual-antiplatelet treatment will be of one month; later all patients will be continued indefinitely on aspirin. Clopidogrel, will be started 48 hours before the procedure with a loading dose of of 300mg and continued at 75mg/day; aspirin will be given at the dose of 100-325mg/day. Platelet reactivity assessment will be carried-out: before intervention, after 1 week of treatment, after 1 month of treatment after 1 year. All patients will be recalled for clinical examination at 1 and 6 months and at 1 year.

Official Title
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Observational Study on Predictive Value for Vascular Events of Residual Platelet Aggregation in Patients on Antiplatelet Therapy After Carotid Angioplasty With Stenting

Conditions
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Carotid Artery Disease

Intervention / Treatment
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* Drug: Aspirin plus clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Informed written consent No contraindications to dual-antiplatelet treatment Exclusion criteria Age < 18 or > 80 years old Use of oral anticoagulants Use of dipyridamole, cilostazol, NSAIDs Myeloproliferative syndrome or paraproteinemia Liver or kidney failure Thrombocytopathies Platelets count < 100000 or > 450000/µl Haemoglobin < 8g/dl

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Aspirin plus clopidogrel<br>Patients undergoing stenting for critical carotid stenosis, either symptomatic (previous events of cerebral ischemia) or asymptomatic, undergoing CAS. | Drug: Aspirin plus clopidogrel<br>* Clopidogrel, will be started 48 hours before the procedure with a loading dose of of 300mg and continued at 75mg/day. Aspirin will be given at the dose of 100-325mg/day.<br>* Other names: Plavix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Platelet reactivity | assessed by VerifyNow (ASA and P2Y12 cartridges), Multiplate (ASA and ADP cartridges), PFA100 (coll/epi; coll/adp; coll/P2Y12 cartridges) | 1, 6 and 12 months | 
| Change in Occurrence of stroke | assessed by subsequent follow-up | 1, 6 and 12 months | 
| Change in Occurence of myocardial infarction | assessed by subsequent follow-up | 1, 6 and 12 months | 
| Change in occurrence of lower limb ischemia | assessed by subsequent follow-up | 1, 6 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Incidence of restenosis | assessed by Eco Color Doppler | 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carotid stenosis, Aspirin plus Clopidogrel, Residual platelet reactivity