Extracranial-intracranial arterial bypass surgery failed to prevent the recurrence of ischemic stroke any better than did medical therapy alone in a large clinical trial of patients with atherosclerotic internal carotid artery occlusion.
Even though graft patency was deemed "excellent" and the surgery clearly improved cerebral hemodynamics, the rate of ipsilateral recurrent stroke after 2 years was approximately 21%, which was not significantly different from the 23% rate among patients who received only medical therapy, Dr. William J. Powers of the department of neurology at the University of North Carolina at Chapel Hill, and his associates reported online Nov. 8 in JAMA.
Extracranial-intracranial (EC-IC) bypass surgery is designed to prevent recurrent stroke by improving hemodynamics distal to an index atherosclerotic occlusion in the internal carotid artery. Dr. Powers and his colleagues conducted the COSS (Carotid Occlusion Surgery Study) to determine whether the procedure, when added to optimal medical therapy, further reduced the rate of ipsilateral ischemic stroke.
They enrolled 195 patients who demonstrated complete occlusion of an internal carotid artery on vascular imaging, had experienced a transient ischemic attack (TIA) or ischemic stroke in the hemispheric territory of the occluded artery during the preceding 120 days, and showed hemodynamic cerebral ischemia on PET measurement of oxygen extraction fraction. The study subjects were randomly assigned to receive medical therapy (98 patients) or medical therapy plus EC-IC bypass surgery (97 patients) at 49 clinical centers and 18 PET centers in the United States and Canada.
The bypass surgery clearly improved cerebral hemodynamics on follow-up assessments, and overall graft patency was 98% after 30 days and 96% at last follow-up.
The 21% rate of recurrent ipsilateral ischemic stroke in the surgical group was very close to the rate of 24% that was predicted when the trial was designed, but the nonsurgical group’s rate of 23% was markedly lower than the 40% rate that had been predicted for it, based on the results of prospective observational studies performed in the 1990s. So even though the EC-IC bypass surgery cut the risk of recurrent stroke, "the better-than-expected efficacy of medical therapy in the nonsurgical group was sufficient to nullify any overall benefit of surgery," the investigators wrote (JAMA 2011;306:1983-92).
"Interpretation of the study is limited by the relatively small number of outcomes events," they added.
The COSS trial was terminated early when an interim analysis showed that given the unexpectedly low number of primary end points in the nonsurgical group, a clinically meaningful difference in favor of surgery would not be detectable unless the sample size were markedly increased. Since this wasn’t feasible, the investigators ended the study.
Later, a significant error was discovered in the interim analysis. However, it was still "highly unlikely that the COSS would have shown a statistically significant benefit for surgery if taken to completion," Dr. Powers and his associates noted.
The COSS trial was funded by grants from the National Institute of Neurological Disorders and Stroke and the U.S. Public Health Service. Several of Dr. Powers’ associates reported receiving personal compensation as a consultant for Merck, Medtronic, and W.L. Gore and Associates.
Dr. Broderick and Dr. Meyers are involved in the IMS III trial, which receives or has received interventional devices or drugs from Genentech, EKOS Corp., Concentric, and Johnson & Johnson. Dr. Broderick also reported serving as a consultant to Genentech and receiving investigational drug supply for the ongoing CLEARER trial from Schering Plough.