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Circulation. 2007;116:1497-1503
Published online before print September 10, 2007, doi: 10.1161/CIRCULATIONAHA.107.716407
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(Circulation. 2007;116:1497-1503.)
© 2007 American Heart Association, Inc.


Vascular Medicine

Effects of Random Allocation to Vitamin E Supplementation on the Occurrence of Venous Thromboembolism

Report From the Women’s Health Study

Robert J. Glynn, PhD, ScD; Paul M Ridker, MD; Samuel Z. Goldhaber, MD; Robert Y.L. Zee, PhD; Julie E. Buring, ScD

From the Division of Preventive Medicine (R.J.G., P.M.R., R.Y.L.Z., J.E.B.), Center for Cardiovascular Disease Prevention (P.M.R.), and Division of Cardiovascular Medicine (P.M.R., S.Z.G.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; and the Departments of Biostatistics (R.J.G.) and Epidemiology (J.E.B.), Harvard School of Public Health, Boston, Mass.

Correspondence to Robert J. Glynn, Phd, ScD, Division of Preventive Medicine, Brigham and Women’s Hospital, 900 Commonwealth Ave E, Boston, MA 02215-1204. E-mail rglynn{at}rics.bwh.harvard.edu

Received May 19, 2007; accepted July 30, 2007.

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.


 

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