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To the Editor.—Dr Wennberg and colleagues¹ and Dr Cebul and colleagues² demonstrate how misapplied randomized clinical trials might in the end do more harm than good when results achieved on highly selected patients treated at selected institutions are generalized to broader practice. However, the authors did not consider that high-risk patients may be more likely to benefit despite higher operative mortality. As elegantly demonstrated by Rothwell,³ in the European Carotid Surgery Trial, high-risk patients (defined by an independently derived multivariable model that included age, blood pressure, and several comorbidities) were the most likely to benefit from surgery, as their risk of stroke if they were not treated was so great. Low-risk patients, on the other hand, were unlikely to derive any benefit from surgery and may even be harmed, despite the fact that they had symptomatic, high-grade stenosis. Contrary to a common fallacy, there is not a single threshold . . . [Full Text of this Article]

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