Beyond Anticoagulation: Limitations of Oral Anticoagulants in Preventing Stroke Recurrence in Atrial Fibrillation

<b>Background/Objectives</b>: Despite the widespread use of oral anticoagulants (OACs), acute ischemic stroke (AIS) remains a significant risk for patients with atrial fibrillation (AF). The real-world effectiveness of OACs in preventing recurrent strokes, particularly following an initial stroke of cardioembolic (CE) origin, continues to be a major challenge for clinicians managing AF patients. This study evaluated the efficacy of OACs in secondary stroke prevention and investigated the influence of anticoagulation type and quality on recurrence risk. <b>Methods</b>: We analyzed data from 128 AF patients in the prospective Transzlációs Idegtudományi Nemzeti Laboratórium (TINL) STROKE-registry, admitted with CE stroke between February 2023 and September 2024. Patients were categorized by anticoagulation status at admission (OAC-users, <i>n</i> = 89; anticoagulation-naïve, <i>n</i> = 39). Recurrence rates were assessed using logistic regression models, adjusted for age, sex, hypertension, diabetes, and pre-stroke disability. Subgroup analyses explored the effects of anticoagulation type and quality. <b>Results</b>: Recurrence rates were similar between the OAC-treated and anticoagulation-naïve patients after adjusting for confounders (19.10% vs. 17.95%, <i>p</i> = 0.870). Among the anticoagulated patients, neither anticoagulation type nor quality alone significantly influenced the recurrence risk. However, their interaction was statistically significant (<i>p</i> = 0.049), suggesting that the effectiveness of anticoagulation in preventing strokes is strongly affected by treatment quality. <b>Conclusions</b>: Although OACs are a cornerstone of stroke prevention in patients with AF, their efficacy in reducing recurrence depends on optimal management. These findings highlight that adequate anticoagulation, not just its use, is critical to minimize recurrence risk. To effectively prevent strokes in high-risk AF patients, future strategies must focus on standardized protocols, tailored monitoring, and individualized dosing regimens.