Culprit factors for the failure of well-conducted warfarin therapy to prevent ischemic events in patients with atrial fibrillation: the role of homocysteine

Background and Purpose—In patients with atrial fibrillation (AF), oral anticoagulant therapy (OAT) is effective in reducing stroke and embolism. However, despite OAT, ischemic events do occur in some patients. Studies specifically addressing the identification of risk factors for ischemic events during well-conducted OAT are not available. In this study, we prospectively investigated the role of classic risk factors and homocysteine levels in the occurrence of ischemic complications in 364 AF patients on OAT. Methods—The quality of anticoagulation levels and the occurrence of bleeding and thrombotic events were recorded. Results—During follow-up (859 patient years) 21 patients had ischemic complications (rate 2.4_100 patient-years). Homocysteine plasma levels were higher in these patients than in patients without ischemic complications during OAT (P_0.01), whereas no difference was observed in relation to the quality of OAT. The presence of a history of previous ischemic events, hypertension, and homocysteine plasma levels over the 90th percentile were all associated with an increased risk of ischemic events during OAT (odds ratio [OR]_7, 4.5, and 4.7, respectively). The coexistence of these risk factors markedly increased the risk (OR_13.1; 95% CI, 3.7 to 45.7; P_0.001). Conclusion—In conclusion, our results indicate that AF patients with multiple risk factors may not be sufficiently protected by OAT, even when this is well conducted.