Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism - Report from the Women's Health Study

Background-Supplementation with vitamin E may antagonize vitamin K in healthy adults, but it is unclear whether intake of vitamin E decreases the risk of venous thromboembolism (VTE). Methods and Results-The Women's Health Study randomized 39 876 women >= 45 years of age to receive 600 IU of natural source vitamin E or placebo on alternate days. Before randomization, 26 779 participants gave blood samples, which were used to determine factor V Leiden, G20210A prothrombin, and 677C > T MTHFR polymorphisms. Documented VTE ( including deep vein thrombosis or pulmonary embolism) and unprovoked VTE ( no recent surgery, trauma, or cancer diagnosis) were prospectively evaluated, secondary end points of the trial. During a median follow-up period of 10.2 years, VTE occurred in 482 women: 213 in the vitamin E group and 269 in the placebo group, a significant 21% hazard reduction ( relative hazard, 0.79; 95% CI, 0.66 to 0.94; P=0.010). For unprovoked VTE, the hazard reduction was 27% ( relative hazard, 0.73; 95% CI, 0.57 to 0.94; P=0.016). In subgroup analyses, the 3% of participants who reported VTE before randomization had a 44% hazard reduction ( relative hazard, 0.56; 95% CI, 0.31 to 1.00; P=0.048), whereas women without prior VTE had an 18% hazard reduction ( relative hazard 0.82; 95% CI, 0.68 to 0.99; P=0.040). Women with either factor V Leiden or the prothrombin mutation had a 49% hazard reduction associated with vitamin E treatment ( relative hazard, 0.51; 95% CI, 0.30 to 0.87; P=0.014). Conclusions-These data suggest that supplementation with vitamin E may reduce the risk of VTE in women, and those with a prior history or genetic predisposition may particularly benefit.