Research Advances in Timing of Anticoagulant Therapy Following Cardioembolic Stroke

Cardioembolic stroke primarily results from thromboembolism caused by cardiac conditions such as atrial fibrillation, characterised by high recurrence rates, high rates of disability, and high mortality. Anticoagulation therapy is a key measure for the prevention of stroke recurrence, though the timing of its initiation remains debated, requiring a balance between the risk of thromboembolic recurrence and the risk of bleeding. The widely adopted "1-3-6-12-day rule" is based on expert consensus but lacks support from high-level evidence. In recent years, multiple randomized controlled trials (such as TIMING, ELAN, OPTIMAS, and START) have demonstrated that for patients with mild-to-moderate cardioembolic stroke, early initiation (within 2-4 days after stroke) of direct oral anticoagulants (DOACs) is not only safe but also significantly reduces the risk of early recurrence, without increasing the incidence of symptomatic intracranial hemorrhage. In particular, the recently completed individual participant data meta-analysis (CATALYST) has provided robust evidence for early anticoagulation. Unlike previous reviews that have focused solely on the timing of anticoagulation in non-valvular atrial fibrillation, this review provides a critical appraisal of the evidence gaps for severe stroke and post-reperfusion populations, a practical comparison of individual DOACs to guide drug selection, and a summary of management principles for other cardioembolic sources (mechanical valves, infective endocarditis, patent foramen ovale, left ventricular thrombus, and atrial flutter). This review summarises the pathophysiological mechanisms of cardioembolic stroke, clinical strategies for anticoagulation timing, characteristics of different anticoagulant agents and their indications for use. It emphasises the importance of individualised treatment and indicates that future research should further clarify the optimal timing of anticoagulation in patients with severe stroke and those undergoing reperfusion therapy.