Trial Summary:
In one-third of ischemic strokes, a specific cause cannot be identified. Many of these cryptogenic strokes appear to arise from a distant embolic source. Recent evidence suggests that some cryptogenic strokes arise from left atrial thromboembolism that goes unrecognized because it is not associated with atrial fibrillation/flutter (AF). Under the prevailing clinical paradigm, it is thought that AF is required for blood clots to form in the left atrium. Therefore, unless AF is apparent, patients do not receive anticoagulant therapy to prevent atrial thromboembolism. However, recent research indicates that embolization from the left atrium can occur when there are abnormal changes to atrial tissue and function even before there is AF. Such an “atrial cardiopathy” may explain many of the strokes that are currently of unknown cause. Since anticoagulant drugs such as apixaban have already proven more effective than standard aspirin therapy for preventing stroke from AF, the parallels between AF and atrial cardiopathy suggest that apixaban may also be more effective than aspirin for stroke prevention in patients with atrial cardiopathy and no AF.
ARCADIA is a randomized trial of apixaban versus aspirin specifically in patients with cryptogenic stroke who have evidence of atrial cardiopathy. This trial will address several important knowledge gaps. First, it will advance our understanding of stroke pathophysiology by assessing whether atrial cardiopathy is a valid therapeutic target, which may set the stage for a primary prevention trial. Second, this trial will advance our understanding of optimal secondary stroke prevention therapy.