Abstract 5134: Effects of Vitamins C and E and Beta Carotene on the Occurrence of Venous Thromboembolism: A Randomized Trial in Women at High Cardiovascular Risk
Background: Limited observational and randomized evidence suggests that antioxidant intake or supplement use may lower the risk of venous thromboembolism (VTE).
Methods: The Women’s Antioxidant Cardiovascular Study randomized 8,171 female health professionals with a history of cardiovascular disease or 3 or more cardiovascular risk factors to receive 500 mg/d of ascorbic acid or placebo, 600 IU of vitamin E or placebo every other day, and 50 mg beta carotene or placebo every other day, in a 2×2×2 factorial design. Documented VTE (including pulmonary embolism or deep vein thrombosis) and unprovoked VTE (no recent surgery, trauma, or cancer) were prospectively evaluated as secondary endpoints of the trial.
Results: During a median follow-up of 9.4 years, VTE occurred in 219 women for an incidence rate (per 1,000 person-years) of 3.05. This incidence was 90% higher than the age-adjusted rate observed in a parallel trial of vitamin E in female health professionals without CVD that used comparable methods of VTE ascertainment. There was no overall effect of ascorbic acid (hazard ratio [HR], 0.91; 95% CI, 0.70 –1.18, [P=0.47]), vitamin E (HR, 0.93; 95% CI, 0.71–1.21, [P= 0.59], or beta carotene (HR, 1.19; 95% CI, 0.91–1.55, [P=0.21] on occurrence of VTE. Unprovoked VTE occurred in 141 women and similar, non-significant treatment effects were observed for this outcome: ascorbic acid HR, 0.81 (95% CI, 0.58 –1.13); vitamin E HR, 1.00 (95% CI, 0.72–1.40); and beta carotene HR, 1.34 (95% CI, 0.96 –1.88). There were also no significant pairwise interactions between agents on risk, although women who received active vitamin E only or active vitamin C only had observed 42% and 45% reductions, respectively, in the hazard of VTE relative to women receiving all placebo agents, and the reduction was nominally significant for vitamin E only (P=0.038).
Conclusion: There were no overall effects of ascorbic acid, vitamin E, or beta carotene on VTE among women at high risk for cardiovascular disease, although in light of prior evidence and the possible benefits of vitamin E or vitamin C alone, further study of these agents seems warranted.