When anticoagulant therapy is not enough: recurrent stroke.

Despite the use of oral anticoagulants, the residual risk of recurrent ischaemic stroke in patients with atrial fibrillation (AF) is ∼4% per year; however, in patients who experience a stroke despite oral anticoagulant therapy (OAT), this risk approaches 9% per year. It is therefore essential to identify patients at higher risk and to develop new strategies for secondary prevention. These strategies include the exclusion of non-AF-related causes, optimization of OAT and its early initiation after stroke, as well as an aggressive rhythm-control approach. Additional non-pharmacological options include surgical or percutaneous left atrial appendage occlusion, although its effectiveness in secondary prevention after ischaemic stroke is still under evaluation. Novel pharmacological therapies targeting factors XI and XIa are currently under investigation and may provide comparable efficacy with improved safety compared with direct oral anticoagulants. Conversely, switching from one anticoagulant to another or adding antiplatelet therapy is completely ineffective. The mechanisms underlying recurrent stroke despite anticoagulant therapy are therefore complex, making an individualized, patient-specific approach mandatory.