Initial 3-Weeks’ Apixaban Versus Dual-Antiplatelet Therapy (Clopidogrel and Aspirin) Followed by Clopidogrel Alone in High-Risk Patients with Acute Non-Disabling Cerebrovascular Events (ADANCE): Study Protocol for a Randomized Controlled Trial

BACKGROUND: Nondisabling cerebrovascular events represent the largest group of cerebrovascular disease with a high risk of recurrent stroke. A recent trial demonstrated that dual-antiplatelet therapy (clopidogrel and aspirin), compared with aspirin monotherapy, reduced the risk of recurrent stroke and was not associated with increased risk of hemorrhagic events. Apixaban, a new oral anticoagulant, has been proven to be as safe and effective as traditional anticoagulants while carrying significantly less risk of intracranial hemorrhage. Patients with transient ischemic attack (TIA)/minor stroke might benefit from apixaban treatment; therefore, an adequately powered randomized study is needed. METHODS AND RESULTS: The ADANCE [Apixaban Versus Dual-antiplatelet Therapy (Clopidogrel and Aspirin) in Acute Non-disabling Cerebrovascular Events] study is a randomized, double-blind clinical trial with a target enrollment of 5,500 patients. A 21-day regimen of apixaban or of clopidogrel with aspirin followed by clopidogrel on days 22 through 90 will be administered to randomized participants with acute TIA or minor ischemic stroke. The primary efficacy endpoint is the percentage of patients with any new stroke (ischemic or hemorrhage), including fatal stroke, at day 21. Study visits will be performed on the day of randomization, and at days 7, 22, and 90. DISCUSSION: The novel oral anticoagulant apixaban has been widely used with fewer adverse effects than traditional anticoagulants. We designed the ADANCE trial to observe the effects of apixaban on recurrent stroke after TIA or minor stroke. The results should better guide the selection of anticoagulant or dual-antiplatelet therapy for patients with acute TIA or minor ischemic stroke.