Hooman Kamel1, W T Longstreth2,3,4, David L Tirschwell2, Richard A Kronmal5, Joseph P Broderick6, Yuko Y Palesch7, Caitlyn Meinzer7, Catherine Dillon7, Irene Ewing6, Judith A Spilker6, Marco R Di Tullio8, Eldad A Hod9, Elsayed Z Soliman10, Seemant Chaturvedi11, Claudia S Moy12, Scott Janis12, Mitchell Sv Elkind13,14. 1. 1 Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medical College, New York, NY, USA. 2. 2 Department of Neurology, University of Washington, Seattle, WA, USA. 3. 3 Department of Medicine, University of Washington, Seattle, WA, USA. 4. 4 Department of Epidemiology, University of Washington, Seattle, WA, USA. 5. 5 Department of Biostatistics, University of Washington, Seattle, WA. 6. 6 Department of Neurology, University of Cincinnati, Cincinnati, OH, USA. 7. 7 Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA. 8. 8 Department of Medicine, Columbia University, New York, NY, USA. 9. 9 Department of Pathology and Cell Biology, Columbia University, New York, NY, USA. 10. 10 Epidemiological Cardiology Research Center, Department of Epidemiology and Prevention, and Department of Internal Medicine, Section on Cardiology, Wake Forest School of Medicine, Winston-Salem, NC, USA. 11. 11 Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA. 12. 12 National Institutes of Neurological Disease and Stroke, Bethesda, MD, USA. 13. 13 Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA. 14. 14 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Abstract
RATIONALE: Recent data suggest that a thrombogenic atrial substrate can cause stroke in the absence of atrial fibrillation. Such an atrial cardiopathy may explain some proportion of cryptogenic strokes. AIMS: The aim of the ARCADIA trial is to test the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in subjects with cryptogenic ischemic stroke and atrial cardiopathy. SAMPLE SIZE ESTIMATE: 1100 participants. METHODS AND DESIGN: Biomarker-driven, randomized, double-blind, active-control, phase 3 clinical trial conducted at 120 U.S. centers participating in NIH StrokeNet. POPULATION STUDIED: Patients ≥ 45 years of age with embolic stroke of undetermined source and evidence of atrial cardiopathy, defined as ≥ 1 of the following markers: P-wave terminal force >5000 µV × ms in ECG lead V1, serum NT-proBNP > 250 pg/mL, and left atrial diameter index ≥ 3 cm/m2 on echocardiogram. Exclusion criteria include any atrial fibrillation, a definite indication or contraindication to antiplatelet or anticoagulant therapy, or a clinically significant bleeding diathesis. Intervention: Apixaban 5 mg twice daily versus aspirin 81 mg once daily. Analysis: Survival analysis and the log-rank test will be used to compare treatment groups according to the intention-to-treat principle, including participants who require open-label anticoagulation for newly detected atrial fibrillation. STUDY OUTCOMES: The primary efficacy outcome is recurrent stroke of any type. The primary safety outcomes are symptomatic intracranial hemorrhage and major hemorrhage other than intracranial hemorrhage. DISCUSSION: ARCADIA is the first trial to test whether anticoagulant therapy reduces stroke recurrence in patients with atrial cardiopathy but no known atrial fibrillation.
RCT Entities:
RATIONALE: Recent data suggest that a thrombogenic atrial substrate can cause stroke in the absence of atrial fibrillation. Such an atrial cardiopathy may explain some proportion of cryptogenic strokes. AIMS: The aim of the ARCADIA trial is to test the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in subjects with cryptogenic ischemic stroke and atrial cardiopathy. SAMPLE SIZE ESTIMATE: 1100 participants. METHODS AND DESIGN: Biomarker-driven, randomized, double-blind, active-control, phase 3 clinical trial conducted at 120 U.S. centers participating in NIH StrokeNet. POPULATION STUDIED: Patients ≥ 45 years of age with embolic stroke of undetermined source and evidence of atrial cardiopathy, defined as ≥ 1 of the following markers: P-wave terminal force >5000 µV × ms in ECG lead V1, serum NT-proBNP > 250 pg/mL, and left atrial diameter index ≥ 3 cm/m2 on echocardiogram. Exclusion criteria include any atrial fibrillation, a definite indication or contraindication to antiplatelet or anticoagulant therapy, or a clinically significant bleeding diathesis. Intervention: Apixaban 5 mg twice daily versus aspirin 81 mg once daily. Analysis: Survival analysis and the log-rank test will be used to compare treatment groups according to the intention-to-treat principle, including participants who require open-label anticoagulation for newly detected atrial fibrillation. STUDY OUTCOMES: The primary efficacy outcome is recurrent stroke of any type. The primary safety outcomes are symptomatic intracranial hemorrhage and major hemorrhage other than intracranial hemorrhage. DISCUSSION: ARCADIA is the first trial to test whether anticoagulant therapy reduces stroke recurrence in patients with atrial cardiopathy but no known atrial fibrillation.
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