Homocysteine-lowering therapy and risk for venous thromboembolism: a randomized trial.

BACKGROUND

Elevated total homocysteine levels are associated with a higher risk for venous thromboembolism. Whether decreasing homocysteine levels with vitamin therapy reduces the risk for venous thromboembolism is not known.

OBJECTIVE

To determine whether decreasing homocysteine levels alters the risk for symptomatic venous thromboembolism.

DESIGN

Secondary analysis of data from the randomized, placebo-controlled Heart Outcomes Prevention Evaluation 2 (HOPE-2) trial.

SETTING

145 clinical centers in 13 countries.

PARTICIPANTS

5522 persons 55 years of age or older with known cardiovascular disease or diabetes mellitus and at least 1 other risk factor for vascular disease.

INTERVENTION

A daily supplement of 2.5 mg of folic acid, 50 mg of vitamin B(6), and 1 mg of vitamin B(12) or matching placebo for 5 years.

MEASUREMENT

Prospectively diagnosed and confirmed symptomatic deep venous thrombosis or pulmonary embolism.

RESULTS

The geometric mean homocysteine level decreased by 2.2 micromol/L in the vitamin therapy group and increased by 0.80 micromol/L in the placebo group. Venous thromboembolism occurred in 88 participants during a mean follow-up of 5 years. The incidence rate of venous thromboembolism was the same in the vitamin therapy group and the placebo group (0.35 per 100 person-years; hazard ratio, 1.01 [95% CI, 0.66 to 1.53]). Vitamin therapy did not reduce the risk for deep venous thrombosis (hazard ratio, 1.04 [CI, 0.63 to 1.72]), pulmonary embolism (hazard ratio, 1.14 [CI, 0.57 to 2.28]), or unprovoked venous thromboembolism (hazard ratio, 1.21 [CI, 0.66 to 2.23]).

LIMITATIONS

The proportion of patients with a previous episode of venous thromboembolism at enrollment was not known, and venous thromboembolism events were not centrally adjudicated.

CONCLUSION

Decreasing homocysteine levels with folic acid and vitamins B6 and B12 did not reduce the risk for symptomatic venous thromboembolism.