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Homocysteine-Lowering Therapy After Venous Thromboembolism

A randomized trial found that homocysteine lowering with B vitamins did not reduce the risk for recurrence.

Elevated homocysteine levels are associated with both arterial and venous thrombotic events. However, in recent trials, homocysteine-lowering B-vitamin therapy did not prevent arterial events such as myocardial infarction or stroke (Journal Watch Mar 28 2006 and Feb 17 2004). But what about secondary prevention of venous thromboembolism?

European researchers enrolled 701 patients with recent venous thromboembolism (VTE; either proximal deep-vein thrombosis or pulmonary embolism), but without major predisposing risk factors such as recent surgery or immobilization. At baseline, half the patients had hyperhomocysteinemia (mean, 15.5 µmol/L), and half had normal levels (mean, 9.0 µmol/L). Patients were randomized to receive a B-vitamin supplement (5 mg folic acid, 0.4 mg B₁₂, and 50 mg B₆) or placebo, in addition to standard anticoagulation.

During 2.5 years of follow-up, the overall incidence of recurrent VTE was not significantly different in the B-vitamin and placebo groups (5.4% vs. 6.4%). In hyperhomocysteinemic patients, the incidence of recurrent VTE was nonsignificantly higher in B-vitamin recipients than in placebo recipients (6.7% vs. 6.0%); in those with normal homocysteine, the incidence of recurrent VTE was nonsignificantly lower in B-vitamin recipients (4.1% vs. 7.0%).

Comment: In this, the first randomized trial of homocysteine-lowering therapy to prevent recurrent venous thromboembolism, B vitamins did not reduce the risk for recurrence. The authors note that their study might have been underpowered to detect a small beneficial effect. However, they also speculate that homocysteine's observed epidemiologic association with VTE might in fact be mediated by some other thrombophilic factor that is correlated with homocysteine.

— Allan S. Brett, MD

Published in Journal Watch General Medicine February 6, 2007

Citation(s):

den Heijer M et al. Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: A randomized, placebo-controlled, double-blind trial. Blood 2007 Jan 1; 109:139-44.

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