Submitted April 4, 2006
Accepted August 9, 2006
Homocysteine lowering by B vitamins and the secondary
prevention of deep-vein thrombosis and pulmonary
embolism. A randomized, placebo-controlled, double blind
trial
Martin den Heijer*, Huub PJ Willems, Henk J Blom, Wim BJ Gerrits, Marco Cattaneo, Sabine Eichinger, Frits R. Rosendaal, and Gerard MJ Bos
Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Dept. of Hematology, Leyenburg Hospital, The Hague, The Netherlands
Laboratory of Paediatrics and Neurology, Radboud University Nijmegen Medical Centre, Nijmegen
Unit of Hematology and Thrombosis, Ospedale San Paolo, University of Milano, Milano, Italy
Dept. of Internal Medicine I, Medical University of Vienna, Vienna, Austria
Dept. of Clinical Epidemiology and Dept. of Hematology, Leiden University Medical Center, Leiden
Dept. of Hematology, University Hospital Maastricht, Maastricht, The Netherlands
* Corresponding author; email: m.denheijer{at}endo.umcn.nl.
The VITRO (Vitamins and Thrombosis) study investigated the effect of homocysteine lowering by daily supplementation of B-vitamins on the risk reduction of deep-vein thrombosis and pulmonary embolism. Patients between 20 to 80 years old with a first objectively confirmed proximal deep-vein thrombosis or pulmonary embolism in the absence of major risk factors and a homocysteine concentration above the 75th percentile of a reference group were asked to participate (hyperhomocysteinemic group). A similar study was conducted in a random sample of patients with a homocysteine below the 75th percentile of the reference group (normohomocysteinemic group). After informed consent patients were randomized to daily multivitamin supplementation (5 mg folic acid, 50 mg pyridoxine and 0.4 mg cyanocobalamin) or placebo and were followed for 2.5 years. End-points were objectively diagnosed recurrent deep-vein thrombosis or pulmonary embolism. A total of 701 patients were enrolled (360 in the hyper- and 341 in the normo homocysteinemic group). The number of recurrent events of venous thrombosis was 43 out of 353 in the vitamin group (54/1000yr) and 50 out of 348 in the placebo group (64/1000yr ). The hazard ratio associated with vitamin treatment was 0.84 (95%CI 0.56-1.26): 1.14 (95%CI 0.65-1.98) in the hyperhomocysteinemic group and 0.58 (95%CI 0.31-1.07) in the normohomocysteinemic group. The results of our study do not show that homocysteine lowering by B-vitamin supplementation prevents recurrent venous thrombosis. (ClinicalTrials.gov number NCT00314990)
