Grant: Project Grant

One-quarter of all strokes are recurrent strokes. While initial strokes are often mild, recurrent strokes are more severe. The risk of recurrent stroke is best addressed by therapies that specifically target the cause of stroke. Historically, severely decreased ejection fraction (EF) has been considered a cause of embolic stroke. However, the optimal therapy for this form of left ventricular (LV) injury remains uncertain. We have found that a more common form of LV injury, segmental wall motion abnormality (WMA), is also a stroke risk factor. Our preliminary studies suggest that anticoagulation may be superior to standard-of-care aspirin for prevention of stroke due to LV injury, defined as the traditionally recognized but undertreated risk factor of low EF or the emerging novel stroke risk factor, WMA. LV injury is common, found in >25% of patients with ischemic stroke. The goal of this proposal is to determine if anticoagulation with apixaban is superior to standard-of-care aspirin in patients with recent ischemic stroke and LV injury. No prior trial has evaluated anticoagulant therapy in patients with recent stroke and LV injury. A dedicated secondary stroke prevention trial is necessary to answer this question. RESOLVE is a multicentre randomized adaptive double-blind phase 3 trial that will enroll 1200 patients with recent stroke and LV injury. Participants will be randomly assigned to apixaban or aspirin and followed for a minimum of 2 years. The primary outcome is recurrent stroke or systemic embolism. Secondary outcomes are symptomatic intracranial hemorrhage and major systemic hemorrhage. This study will test the hypothesis that anticoagulation will be superior to aspirin at reducing the risk of recurrent stroke or systemic embolism in patients with LV injury. The expected outcome of this research is the determination that anticoagulation is the optimal therapy for patients with recent ischemic stroke and LV injury as a means of preserving brain health.