Stroke Prevention With Abciximab in Carotid Endarterectomy
Stroke Prevention With Abciximab in Carotid Endarterectomy
In the first portion of the study, the goal will be to determine the safety of the drug
 Abciximab for use during and in the period after open carotid artery surgery. In addition,
 using specialized ultrasound equipment (a probe that is placed on the outside of your skin of
 your head), we will aim to measure the number of particles released around the time of
 surgery while being treated with Abciximab. The second phase of the study will be determine
 if Abciximab can safely reduce the number of particles released into the bloodstream around
 the time of surgery in order to reduce the risk of stroke.
Carotid endarterectomy is the most frequently performed vascular procedure in the United
 States. In the last decade, there has been a large increase in case volume following
 confirmation of the efficacy of endarterectomy for carotid artery atherosclerotic disease by
 the NASCET and ACAS trials. Estimates for 1994 suggested that over 130,000 patients underwent
 carotid endarterectomy in the United States.

 Despite the efficacy of endarterectomy over medical management for extra cranial cerebral
 vascular disease, the risk of having an ipsilateral perioperative stroke after carotid
 endarterectomy remains at 2-7%. There are two main types of operation-related stroke. The
 intra-operative stroke is apparent upon recovery from anesthesia and is directly attributable
 to intra-operative ischemia or embolization. The post-operative stroke occurs sometime after
 an uneventful recovery from surgery and is due to vessel occlusion or embolization off the
 thrombogenic endarterectomy surface. Evidence suggests that platelets adhere to the exposed
 collagen of the endarterectomy surface within minutes of restoring flow. The maximal rate of
 adherence appears to be one hour after clamp release. Postoperative strokes are preceded by
 micro-particulate embolization, which can be detected by transcranial Doppler ultrasound.
 There is good correlation between TCD detection of 25 or more emboli in the middle cerebral
 artery distribution during any ten-minute period after surgery and an increased occurrence of
 transient ischemic attack and or stroke. Another study found an embolic rate greater than 50
 per hour predicted stroke in 50% of patients.

 Further study by TCD of the prevalence of post-operative micro particulate thromboembolic
 events after carotid endarterectomy found five percent of patients have sustained
 postoperative embolization. The embolic rate is maximal in the first two hours
 postoperatively and if no evidence is found for embolization by the third post-operative hour
 then it is unlikely to occur thereafter. Infusion of Dextran 40 has been shown to decrease
 the rate of embolization of micro particulate debris.

 Recent success in decreasing thrombotic events in both percutaneous coronary interventions
 and acute myocardial infarction with platelet glycoprotein IIB/IIIA antagonists has
 stimulated interest in furthering the applications of these drugs. A recent randomized
 clinical trial using Abciximab in acute ischemic stroke documented safety when administered
 up to twenty-four hours after stroke onset, with a trend toward improvement in functional
 outcomes. Abciximab has also been used in conjunction with heparin and aspirin in carotid
 artery percutaneous angioplasty and stenting and is thought to potentially reduce recurrent
 stenoses. Unfortunately, the use of platelet IIb/IIIa inhibitors with open surgical
 procedures not been studied due to concerns of bleeding.

 Study Aims:

 Use of a platelet glycoprotein IIb/IIIa antagonist holds great potential for diminishing or
 eliminating the micro particulate embolization seen with TCD and thus helping lower the
 combined operative morbidity and mortality to less than the five percent rate that is
 commonly accepted. Our primary aim is to document the safety and ideal dosing of Abciximab
 for use in open vascular surgery, namely Carotid Endarterectomy. Our secondary aim is to
 evaluate the incidence of perioperative embolic events after carotid endarterectomy as
 monitored by transcranial Doppler with the perioperative administration of Abciximab.
Inclusion Criteria:

 Subjects will be eligible if the following criteria are met:

 -  Ability to provide written informed consent and comply with study assessments for the
 full duration of the study.

 -  Age >18 years

 -  Diagnosis of >75% asymptomatic carotid artery stenosis by ultrasound or angiographic
 evaluation

 -  No contraindication to Abciximab or anticoagulation

 -  Ability to insonate an adequate window for Transcranial Doppler Imaging
 pre-operatively

 -  In women of childbearing capacity a negative pregnancy test

 -  Signed authorization of release of protected health care information

 Exclusion Criteria:

 -  Inability to insonate an ipsilateral window; bilateral monitoring will be performed
 when possible.

 -  CT or MRI positive CVA within past 12 weeks

 -  Active internal bleeding

 -  Recent within six weeks gastrointestinal or genitourinary bleeding of clinical
 significance

 -  Bleeding diathesis

 -  Administration of oral anti-coagulants within seven days unless prothrombin time is
 less than or equal to 1.2 times control

 -  History of CVA within two years or CVA with a significant residual neurological
 deficit

 -  Thrombocytopenia (<100,000 cells/uL)

 -  Recent (within six weeks) major surgery or trauma Intracranial neoplasm, AVM, or
 aneurysm

 -  Severe uncontrolled hypertension

 -  Presumed or documented history of vasculitis

 -  Use of intravenous dextran before PCI or intent to use during an intervention

 -  Known hypersensitivity to any component of ReoPro

 -  Known hypersensitivity to murine proteins