Factors Associated with Ischemic Stroke on Therapeutic Anticoagulation in Patients with Nonvalvular Atrial Fibrillation

PURPOSE: In this study, we investigated the stroke mechanism and the factors associated with ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF) who were on optimal oral anticoagulation with warfarin. MATERIALS AND METHODS: This was a multicenter case-control study. The cases were consecutive patients with NVAF who developed cerebral infarction or transient ischemic attack (TIA) while on warfarin therapy with an international normalized ratio (INR) ≥2 between January 2007 and December 2011. The controls were patients with NVAF without ischemic stroke who were on warfarin therapy for more than 1 year with a mean INR ≥2 during the same time period. We also determined etiologic mechanisms of stroke in cases. RESULTS: Among 3569 consecutive patients with cerebral infarction or TIA who had NVAF, 55 (1.5%) patients had INR ≥2 at admission. The most common stroke mechanism was cardioembolism (76.0%). Multivariate analysis demonstrated that smoking and history of previous ischemic stroke were independently associated with cases. High CHADS2 score (≥3) or CHA(2)DS(2)-VASc score (≥5), in particular, with previous ischemic stroke along with ≥1 point of other components of CHADS(2) score or ≥3 points of other components of CHA(2)DS(2)-VASc score was a significant predictor for development of ischemic stroke. CONCLUSION: NVAF patients with high CHADS(2)/CHA(2)DS(2)-VASc scores and a previous ischemic stroke or smoking history are at high risk of stroke despite optimal warfarin treatment. Some other measures to reduce the risk of stroke would be necessary in those specific groups of patients.