Secondary prevention of recurrent ischemic stroke: from guidelines to precision medicine

Recurrent ischemic stroke remains a major global health challenge, accounting for substantial disability and mortality despite advances in acute management. Secondary prevention has undergone a fundamental paradigm shift-from standardized, population-based regimens toward individualized, mechanism-targeted precision medicine. This review integrates evidence from recent AHA/ASA and ESO guidelines^[2,3] and landmark clinical trials including NAVIGATE ESUS^[5], RE-SPECT ESUS^[6], CHANCE-2^[2,13], INSPIRES^[18], and COMPASS^[24], highlighting how etiological diagnosis and multimodal risk stratification have reshaped secondary prevention strategies. In Embolic Stroke of Undetermined Source (ESUS), empirical anticoagulation has given way to systematic etiological investigation guided by advanced imaging and biomarkers. For non-cardioembolic stroke, dual antiplatelet therapy (DAPT) exemplifies precision in patient selection, timing, and pharmacogenomic-guided drug choice. Direct oral anticoagulants (DOACs) have become the standard for atrial fibrillation-related stroke and are being explored for broader vascular protection, while lipid management now pursues earlier, lower, and more intensive LDL-C targets through combination therapy. Finally, emerging fields-including metabolomics, genomics, and artificial intelligence-are driving the next generation of risk prediction and individualized therapeutic optimization; yet a substantial translational gap persists between these research advances and their routine clinical operationalization, a theme this review addresses explicitly throughout. Together, these developments define the future landscape of precision secondary prevention, bridging evidence-based guidelines with personalized vascular medicine.