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BMJ. 2007 June 16; 334(7606): 1244–1245.
PMCID: PMC1892460
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Lowering homocysteine doesn't reduce the risk of thromboembolism

Observational studies have found an association between raised total homocysteine concentrations in the serum and venous thromboembolism. Homocysteine is thought to promote thrombosis by enhancing platelet aggregation, increasing thrombin generation, impairing fibrinolysis, and causing endothelial dysfunction.

A placebo controlled trial carried out in 145 centres in 13 countries enrolled more than 5500 people who were over 55 years, had cardiovascular disease or diabetes mellitus, and had at least one other risk factor for atherosclerosis. Patients were randomised to a daily supplement of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 or placebo and were followed up for five yearsyears.

figure scut1606.f2

As expected, the intervention decreased total plasma homocysteine concentrations, but this wasn't coupled with a change in the risk for symptomatic deep venous thrombosis or pulmonary embolism. In the intervention group, the mean plasma homocysteine value decreased by 2.2 µmol/l, while it increased by 0.80 µmol/l in the group randomised to placebo. Nonetheless, compared with the group that received placebo, people who received the vitamins had a hazard ratio of 1.01 (95% CI 0.66 to 1.53) for venous thromboembolism, 1.04 (0.63 to 1.72) for deep venous thrombosis, and 1.14 (0.57 to 2.28) for pulmonary embolism.

Thus, decreasing homocysteine concentrations with folic acid and B vitamins did not reduce the risk of symptomatic venous thromboembolism in these patients. Because the lack of efficacy of this treatment was independent of plasma concentrations of homocysteine in this trial's population, measuring plasma homocysteine in older adults with thromboembolism may not be justified. It may still make sense in children and young adults with venous thromboembolism or arterial thrombosis, the authors say.

References

  • Ann Intern Med 2007;146:761-7 [PubMed]

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