Vitamin E Serum Levels and Bleeding Risk in Patients Receiving Oral Anticoagulant Therapy: a Retrospective Cohort Study

BACKGROUND: Hemorrhagic risk assessment is a crucial issue in patients with nonvalvular atrial fibrillation (NVAF) who are receiving oral anticoagulant therapy (OAT). Our aim was to analyze the relationship between vitamin E, which possesses anticoagulant properties, and bleeding events in NVAF patients. METHODS AND RESULTS: In this retrospective observational study we analyzed baseline serum cholesterol‐adjusted vitamin E (vit E/chol) levels in 566 consecutive patients (59% males, mean age 73.6 years) receiving OAT followed up for a mean time of 22 months. Mean time in therapeutic INR range (TTR) was 64%. The overall incidence rate of any bleeding event was 9.2/100 person‐years. Compared to patients who did not bleed, those who experienced bleeding events (n=92, 73 minor and 15 major bleedings and 4 cerebral hemorrhages according to International Society on Thrombosis and Haemostasis [ISTH] ) classification) showed a significant difference for history of coronary heart disease (P=0.039), HAS‐BLED score (P=0.002), and vit E/chol levels (P<0.001). Higher vit E/chol serum levels were found in patients who bled compared to those who did not (5.27±1.93 versus 4.48±1.97 μmol/cholesterol; P<0.001), with a progressive increase from minor (5.16±1.91 μmol/mmol cholesterol, P=0.006) to major bleedings (5.72±2.0 μmol/mmol cholesterol, P=0.008). A Cox proportional hazard model demonstrated that serum vit E/chol quartiles (global P=0.0189) and HAS‐BLED scores (P=0.005) predicted bleeding events. CONCLUSIONS: In a NVAF population being treated with warfarin, serum vitamin E predicted hemorrhagic events. Further study is necessary to see if the relationship between serum levels of vitamin E and bleeding is still maintained with the use of new anticoagulants. CLINICAL TRIAL REGISTRATION: URL: ClinicalTrials.gov. Unique identifier NCT01882114.