Letter by Powers Regarding Article, “Failure of Cerebral Hemodynamic Selection in General or of Specific Positron Emission Tomography Methodology? Carotid Occlusion Surgery Study (COSS)”
To the Editor:
On behalf of the Carotid Occlusion Surgery Study (COSS) investigators, I would like to respond to Carlson et al in their article concerning the COSS.1
They have incorrectly stated that the oxygen extraction fraction (OEF) ratio threshold used to determine eligibility for COSS as 1.12. It was 1.13. This error is understandable because the article was accepted for publication (June 6, 2011) before the publication of COSS with its final methodology (November 9, 2011).2 However, it is difficult to understand how peer review of this article criticizing the methodology of COSS could have been carried out properly before the final trial methodology and results were available.
We question the relevance to COSS of the positron emission tomography data on 14 patients presented by the authors because these patients must have been clinically ineligible for COSS. As participating institutions in COSS, both the University of New Mexico and the University of Pittsburgh agreed to follow the COSS protocol, which states that all clinically eligible participants will be referred to COSS and that COSS data available locally may not be published without approval of the Executive Committee. Because there was no request from these investigators to publish COSS data, we must conclude that these 14 patients were clinically ineligible for COSS and the data presented are not relevant to the patients enrolled in COSS.
We do have data that allow us to specifically address the issue raised by Carlson et al about whether a 50% quantitative OEF threshold is superior to the count-based ratio method used in COSS. Our data come from 36 subjects with symptomatic internal carotid artery occlusion enrolled in a previous study of prognosis in medically treated subjects who met the clinical eligibility criteria for COSS of hemispheric symptoms within 120 days.3 Quantitative measurements of OEF with arterial catheterization were compared with count-based OEF ratios calculated identically to those subjects enrolled in COSS. We agree with Carlson et al that these methods do not identify the same patients. However, in contrast to Carlson et al who only speculate that the quantitative threshold of 50% better identifies patients at high risk of stroke on medical therapy than the COSS ratio method, we have follow-up data to test this hypothesis. Of these 36 patients, 9 had subsequent ipsilateral stroke. The quantitative OEF threshold only identified 4 of these, whereas the COSS ratio method identified 7, including all 4 identified by the quantitative threshold. The risk of subsequent stroke in patients who met the COSS ratio criteria (7 of 18 [39%]) was virtually identical to those with quantitative OEF ≥50% (4 of 10 [40%]). Because the COSS criteria identified more patients (7 of 9) who would go on to develop a stroke that the absolute OEF criteria (4 of 9), it is the superior method for identifying patients with hemodynamic comprise who are at high risk for subsequent stroke.
As we stated in the publication of the COSS trial, improved hemodynamics in those who underwent extracranial–intracranial bypass surgery without perioperative stroke was associated with low risk of recurrent stroke. However, the risks of surgery and the better-than-expected efficacy of medical therapy in the nonsurgical group were sufficient to nullify any overall benefit in the surgical group.2 There are many possible reasons for the better-than-expected outcome of the nonsurgical group, but our data presented here show that it was not caused by a failure to use an quantitative OEF threshold of 50% instead of the COSS ratio method.
William J. Powers, MD
Department of Neurology
University of North Carolina at Chapel Hill
Chapel Hill, NC
Sources of Funding
This research was supported by US Public Health Service grants NS28947, NS39526, NS42157 and NS41895 from the National Institutes of Neurological Disorders and Stroke.
W.J.P. received salary and other support from the grants.
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- © 2012 American Heart Association, Inc.