Platelet Inhibition and Transcranial Doppler (TCD)-Detected Microemboli During and After Carotid Artery Stenting (CAS) in Asymptomatic Patients Prior to Cardiac Surgery
Condition: Carotid Stenosis
MeSH terms: Carotid Stenosis
Study type: Interventional
Phase: Phase 4

Summary: 
      As with coronary artery stenting, activation and embolisation of platelets occurs with
      carotid artery stenting (CAS). Based on promising data on the use of clopidogrel plus aspirin
      in coronary stenting this dual antiplatelet regimen has been introduced as adjunctive
      treatment during CAS. There is as yet, however, no randomized controlled trial which compared
      different loading doses of clopidogrel during CAS. Taking into account that a wide
      interindividual variability in the response to a loading of clopidogrel exists, this study is
      intended to establish the optimal loading dose of clopidogrel. Therefore platelet function
      testing and a 1-hour of postprocedural TCD (transcranial doppler) monitoring will be
      performed.

      Objective: Firstly, to investigate whether the absolute magnitude of Platelet Inhibition
      inversely correlates with the number of TCD-detected microemboli during and after CAS in
      patients who are being pre-treated with either a 300 mg or a 600 mg loading dose of
      clopidogrel. Secondly, if there is any impact on early neurological outcome determined by the
      loading dose of clopidogrel.
    

Detailed description: 
      Carotid angioplasty with stent placement (CAS) has become a well-accepted treatment option
      for carotid artery stenosis. In combination with experience in CAS procedures and the
      introduction of protection devices and low-profile systems, the periprocedural risk of
      thromboembolic complications are comparable to that of standard surgical carotid
      endarterectomy (CEA) In our centre, all patients with severe asymptomatic carotid artery
      disease ( luminal diameter reduction of more than 80%, according to NASCET criteria)
      scheduled for cardiac surgery are eligible for CAS.

      As with coronary artery stenting , activation and embolisation of platelets occurs with CAS.
      Based on promising data on the use of clopidogrel plus aspirin in coronary stenting, this
      dual antiplatelet regimen has been introduced in CAS. Specifically, an antiplatelet regimen
      with aspirin(300mg) and a 300 mg loading dose of clopidogrel at least 24 hours before carotid
      angioplasty has currently been the treatment of choice in carotid angioplasty with stent
      placement.

      However, several studies have reported a wide interindividual variability in the response to
      a 300 mg loading of clopidogrel with a subsequent substantial proportion of patients not
      receiving the optimal benefit from it. Therefore, it has been suggested that a 600 mg loading
      dose will result in a faster onset, a higher responsiveness and a higher magnitude of
      platelet inhibition without any increase in bleeding complications. For these reasons, the
      interventional cardiology has already adopted the 600 mg loading dose regimen as standard of
      care during percutaneous coronary interventions. There is as yet, however, no randomized
      controlled trial which compared different loading doses of clopidogrel during CAS.

      Using transcranial Doppler (TCD) monitoring of the middle cerebral artery during CAS, it is
      possible to register the number of TCD-detected microembolic signals during and after CAS.
      This monitoring enables the operator to diminish the risk of stroke during CAS. However, a
      significant number of patients develop an ischemic stroke in the hours following CAS after a
      symptom-free interval As published by van der Schaaf et al., in TCD monitoring after CEA, one
      hour of monitoring appeared to be effective to select those patients in whom the number of
      microemboli did not spontaneously decrease. More important, postoperative TCD monitoring was
      able to detect those patients who were at risk for new adverse cerebral events after the
      operation. Other studies demonstrate the potential application of ultrasonic emboli detection
      to examine the efficacy of new platelet agents in relatively small number of patients.

      It remains to be established whether a higher magnitude of platelet inhibition before CAS has
      an additional protective effect by decreasing the microembolic load measured on TCD after the
      procedure. Moreover, such a TCD-monitoring post-CAS has not been performed systematically in
      the past and thus could reveal valuable information helpful to the understanding of post
      procedural cerebral complications and risk stratification.
    

Intervention name(s): Clopidogrel
Intervention type(s): Drug
Intervention description(s): All patients will receive a loading dose of 600mg of study medication. The first group will receive 300 mg of clopidogrel and 300 mg placebo, the second group will receive 600mg of clopidogrel at least 24h before carotid stenting
Intervention MeSH terms: Clopidogrel
Primary purpose: Treatment
Keywords: Platelet Aggregation Inhibitors; Coronary Artery Bypass Grafting