Secondary Prevention Strategies for Ischemic Stroke in Antiphospholipid Syndrome

Introduction: Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder associated with both venous and arterial thrombosis, most notably ischemic stroke. Patients face a high risk of recurrence, and yet optimal strategies for secondary prevention remain uncertain. Methods: We conducted a narrative review of the literature on secondary prevention of ischemic stroke in APS. We performed a comprehensive literature search of PubMed for English-language articles on secondary stroke prevention in APS. Studies were included if they were original human research (e.g., randomized trials, cohort, or case-control studies) or relevant reviews addressing APS-related stroke prevention. Results: Vitamin K antagonists (VKAs) remain the standard of care for high-risk patients with arterial events. Several randomized controlled trials demonstrated higher recurrence rates, particularly of stroke, among APS patients treated with direct oral anticoagulants (DOACs). The optimal target INR remains debated; pooled analyses suggest no clear advantage of high-intensity anticoagulation (INR 3-4) over standard-intensity (INR 2-3), but individualized adjustment is warranted in select cases. In patients with recurrence despite adequate anticoagulation, adding an antiplatelet agent may be beneficial, although supporting evidence is limited. Adjunctive statin therapy shows promise in reducing endothelial dysfunction and prothrombotic markers, with observational data suggesting a possible protective effect, although randomized evidence is lacking. In addition, patent foramen ovale (PFO) closure has been proposed in selected APS patients with paradoxical embolisms, particularly when combined with anticoagulation. Non-pharmacological strategies, including structured lifestyle modification and rigorous vascular risk-factor management, are strongly recommended, as traditional cardiovascular risk factors synergistically increase recurrence risk. Conclusions: Secondary prevention of ischemic stroke in APS requires an individualized approach. VKAs remain first-line, with consideration of antiplatelet add-on, statins, lifestyle interventions, and PFO closure in appropriate settings. Future well-designed clinical trials are needed to refine INR targets, validate combination strategies, and clarify the role of adjunctive therapies in this complex patient population.