Carotid Revascularization Endarterectomy Versus Stenting Trial

The primary aim of the Carotid Revascularization Endarterectomy versus Stenting Trial
(CREST) is to contrast the relative effectiveness of carotid artery stenting (CAS) versus
carotid endarterectomy (CEA) in preventing stroke, myocardial infarction, and death. Stents
are medical devices approved and commonly used for treatment of heart disease. The stent
that will be used in this trial is the Rapid Exchange(RX) ACCULINK(TM) Carotid Stent System,
an elastic-like metal scaffold that is expanded inside a carotid artery to hold the vessel
open.

The RX ACCUNET(TM) Embolic Protection System (an umbrella-like device that expands above the
narrowed portion of the carotid artery) will be used in conjunction with the RX ACCULINK
stent. The RX ACCUNET system is designed to capture embolic material that could break off
from the narrowed area in the carotid artery while still allowing blood to flow through the
vessel during the procedure. Embolic material could block blood flow to the arteries beyond
the narrowing and be harmful to the brain. The RX ACCUNET System is closed and removed after
the stent is placed.

CEA involves a neck incision and physical removal of the plaque from the inside of the
artery. CAS involves insertion of a catheter or tube into an artery in the groin and then
threading the catheter through the arteries of the body to the location of the plaque within
the carotid artery in the neck. The stent is then placed to cover the plaque and hold the
artery open. Participants will be randomly assigned to undergo either CAS or CEA, and all
patients will receive best medical management, which includes treatment with aspirin,
treatment of high blood pressure, and treatment of other stroke risk factors. Participants
will be followed for up to ten years.

With the simplification of the protocol for long-term follow-up, the focus for secondary
outcomes is to assess restenosis and viability of the procedure. Restenosis rates on an
annual basis in both the endarterectomy and stenting arms of the study will be assessed
using carotid duplex ultrasound exams performed annually (standard of care).

In addition to restenosis, the "viability" of the procedures will be assessed by the need
(or lack of need) for repeat revascularization (either open surgical or endovascular) after
the index procedure. The question "has a new carotid intervention been performed since last
follow-up" will be asked at every contact with the patient. If answered positively,
additional data will be collected on the appropriate case report forms(CRFs).

LINKAGE OF CREST COHORT WITH CENTERS FOR MEDICAID AND MEDICARE SERVICES(CMS) ADMINISTRATIVE
DATA

The purpose of linking Medicare-eligible CREST participants with CMS data files is to assess
patient outcomes and utilization of health care services. This plan to link in- and
out-patient episodes of care using national Medicare data establishes a new resource that
will enhance current follow-up strategies, as well as explore alternative strategies to
ascertain patient outcomes for future clinical studies.

Inclusion Criteria:

- Symptomatic patients with recent neurological events (TIA or non-disabling stroke)
with an associated carotid stenosis greater than or equal to 50% by angiography or
greater than or equal to 70% by ultrasound or greater than or equal to 70% by
Computed Tomography Angiography (CTA) or Magnetic Resonance Angiography (MRA) are
eligible for randomization.

- Asymptomatic patients with no recent (in the last 6 months) neurological events
referable to the study with artery and carotid stenosis (patients with symptoms
beyond 180 days are considered asymptomatic) greater than or equal to 60% by
angiography or greater than or equal to 70% by ultrasound or greater than or equal to
80% by CTA or MRA are eligible for randomization.

Exclusion Criteria:

- Conditions that: (1) interfere with the evaluation of endpoints, (2) are known to
interfere with the completion of CEA or CAS, or (3) affect the likelihood of survival
for the study period (4 years). Chronic atrial fibrillation and/or anti-coagulation
or episodic atrial fibrillation within the last 6 months.