Edip Gurol, MD, Massachusetts General Hospital and Harvard Medical School, Boston, MA, discusses the challenges associated with preventing ischemic stroke in patients with atrial fibrillation treated with direct oral anticoagulants. Dr Gurol explains these medications’ failures in preventing stroke and then discusses a multi-center observational study evaluating oral anticoagulant failure in patients with atrial fibrillation. Currently, there are not very efficient approaches to preventing ischemic stroke in patients who have previously failed oral anticoagulants. Therefore, there is a need to improve diagnostics and plan randomized trials to compare therapeutic agents and choose the best treatment approaches for these patients. This interview took place at the American Academy of Neurology 2022 Congress in Seattle, WA.