Approximately 730,000 first-ever or recurrent strokes occur each year in the United States. Ten to fifteen per cent of patients presenting with carotid territory stroke or transient ischemic attacks (TIA) are found to have carotid occlusion. This results in an estimated 61,000 first ever strokes and 19,000 TIAs per year in the United States that are associated with carotid occlusion. Prevention of subsequent stroke in patients with carotid artery occlusion remains a difficult challenge. The overall rate of subsequent stroke is 7% per year for all stroke and 5.9% per year for ischemic stroke ipsilateral to the occluded carotid artery (Cerebrovasc Dis 1991;1:245-256). These risks persist in the face of platelet inhibitory drugs and anticoagulants (JAMA 1998; 280:1055-1060).

The technique of extracranial-intracranial (EC/IC) arterial bypass surgery was developed in the late 1960s and applied to patients with carotid occlusion in an attempt to prevent subsequent stroke by improving the hemodynamic status of the cerebral circulation distal to the occluded vessel. In 1977, an international multicenter randomized trial was begun to determine the efficacy of EC/IC bypass for the prevention of subsequent stroke (N Engl J Med 1985;313:1191-1200). Among 808 patients with symptomatic carotid occlusion who were randomized, no benefit of the surgery could be demonstrated. Based on the results of this well-conducted trial, EC/IC bypass was generally abandoned as a treatment for symptomatic carotid artery occlusion. This trial has, however, been criticized for failing to identify and separately analyze the subgroup of patients with hemodynamic compromise in whom surgical revascularization might be more beneficial. Unfortunately, at the time that this trial was conducted, there was no reliable and proven method for identifying a subgroup of patients in whom cerebral hemodynamic factors were of primary importance in causing subsequent stroke.

Modern neuroimaging techniques have now made it possible to evaluate cerebral hemodynamics in patients with carotid occlusion. Two prospective natural history studies have demonstrated that patients with symptomatic carotid artery disease who have increased oxygen extraction fraction (OEF) measured by PET have a high rate of subsequent stroke within the next two years if maintained on medical therapy. Depending on the precise clinical and PET criteria used, the two-year ipsilateral stroke rates ranged from .26 to .57 (JAMA 1998; 280:1055-1060; Radiology 1999; 212:499-506, J Nucl Med 1999; 40:1992-1998) In contrast, the comparable stroke rates in the patients with normal OEF were .05 to .15, corresponding to absolute rate reductions of .21 to .42 and relative rate reductions of 75 to 80%. EC/IC bypass has been shown to return areas of increased OEF to normal in patients with carotid occlusion, but its effect on the subsequent risk of stroke in these patients is unknown. If the subsequent risk of stroke in patients with symptomatic carotid occlusion and ipsilateral increased OEF who undergo EC/IC bypass is the same as those in whom OEF was normal to start with, then surgery has the potential to produce an absolute rate reduction of .13 to .33 and a relative rate reduction of 40-50% in the subsequent occurrence of stroke within two years in these patients, even taking into account the peri-operative risk of 12.2% found in the EC/IC Bypass Trial. It is appropriate at this time to perform a new trial of EC/IC bypass surgery restricted to patients with symptomatic carotid occlusion and increased OEF identified by PET.