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Results from the Carotid Occlusion Surgery Study (COSS; NCT00029146), presented by William Powers, MD, University of North Carolina, Chapel Hill, North Carolina, failed to show an overall benefit on 2-year stroke recurrence when extracranial-intracranial (EC-IC) bypass surgery was added to standard medical therapy.

The COSS study was a prospective, randomized, blinded endpoint, controlled trial in which subjects with a recent (≤120 days) symptomatic, ipsilateral hemisphere carotid territory transient ischemic attack or mild-to-moderate ischemic stroke (Barthel index >12/20) were randomly assigned to standard medical treatment plus EC-IC (n=97) or medical treatment only (n=98). All subjects were required to have occlusion of an internal carotid artery, as detected by contrast arteriography; vessels that were suitable for anastomosis; and a PET O¹⁵O/H₂ ¹⁵O count-based ratio image with an ipsilateral-to-contralateral oxygen extraction fraction (OEF) ratio >1.130. The primary study endpoint was a combination of all stroke and death at 30 days from randomization for the medical-only group or from the day of surgery for the surgical group plus ipsilateral ischemic stroke within 2 years.

For the medical-only group, the investigators projected a 40% rate of ipsilateral stroke, based on data from medically treated patients with high OEF in the St. Louis Carotid Occlusion Study [Grubb RL et al. JAMA 1998]. For the combined group, the investigators projected a 24% rate of ipsilateral stroke, based on surgical morbidity and mortality from the EC-IC Bypass Trial [EC-IC Bypass Group. N Engl J Med 1985] and medically treated patients with normal OEF in the St. Louis Carotid Occlusion Study.

The first subject was enrolled in July 2002. Of the 4967 subjects who were screened, 705 were enrolled for PET and 195 were randomized to treatment. COSS was stopped in June 2010 for two reasons: the prespecified boundary for futility to determine a clinically meaningful difference had been reached, and there was an unexpectedly low rate of observed primary endpoints in the medically treated group. Dr. Powers presented the results of the intent-to-treat analysis, which was based on all 195 randomized patients.

With the exception of systolic blood pressure, which was significantly (p=0.02) higher in the medical treatment-only group (139+20 mm Hg vs 133+20 mm Hg in the combined treatment group), the baseline characteristics for the two groups were similar.

A total of 93 subjects (93/98; 95%) received surgery. The mean time from randomization to surgery was 10+13 (SD) days. Thirty-day graft patency was 98%, and patency at last follow-up was 96%. Mean ipsilateral-contralateral OEF ratio improved from 1.258 at baseline to 1.109 at 30 days in the surgical group (data for 87 of 93 subjects). Fourteen subjects in the surgical group experienced the primary endpoint of ipsilateral ischemic stroke in the 30-day postoperative period (one fatal). None occurred between randomization and surgery. This perioperative stroke rate of 15% was not significantly different from the EC-IC Bypass Trial. Six additional surgical patients experienced an endpoint ipsilateral stroke, yielding a 2-year primary endpoint rate in the surgical group of 21%. In the nonsurgical group, the 2-year primary endpoint rate was 23%. This difference was not statistically significant (p=0.7279; 95% CI [for the true difference],- 0.104 to 0.141).

In 1985, the EC-IC Bypass Trial demonstrated no benefit of bypass surgery to prevent recurrent stroke in a study of 1377 patients, including the subgroup of 808 with symptomatic carotid artery occlusion. At the time this trial was designed, there was no proven method for identifying patients for whom hemodynamic factors were of primary importance in the pathogenesis of recurrent stroke. Since that time, advances in medical imaging have made it possible to identify patients who are at high risk of recurrent stroke due to hemodynamic factors. COSS was designed to determine if EC-IC bypass could reduce subsequent ipsilateral ischemic stroke in a select group of patients with symptomatic carotid artery occlusion who were at high risk due to poor effective collateral circulation (high OEF). Based on the results of this study and the original EC-IC Bypass Trial, EC-IC should not be employed as a treatment to prevent stroke recurrence in patients with presumed atherosclerotic carotid occlusion, even when imaging demonstrates poor cerebral perfusion.

• © 2011 MD Conference Express