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Homocysteine-Lowering Therapy in Stroke Patients: No Benefit

B vitamins appear to be of limited value in secondary cardiovascular prevention.

Because high plasma total homocysteine levels are associated with vascular disease, researchers are examining whether homocysteine-lowering therapy improves clinical outcomes. In recent trials, folic acid reduced the restenosis rate after coronary angioplasty (Journal Watch Sep 6 2002), but it did not prevent vascular events in patients with stable coronary disease (Journal Watch Aug 15 2003).

In this multicenter double-blind randomized study, researchers enrolled 3680 patients with nondisabling, nonembolic ischemic strokes and total homocysteine levels above the 25th percentile for the North American stroke population. Patients received either high doses of homocysteine-lowering vitamins (2.5 mg folic acid, 25 mg pyridoxine, and 0.4 mg cobalamin) or low doses that would not be expected to lower homocysteine significantly (20 µg, 200 µg, and 6 µg, respectively). During 2 years of follow-up, mean total homocysteine decreased from 13.4 µmol/L to about 11 µmol/L in the high-dose group and changed only minimally in the control group. However, no reductions were noted in rates of recurrent stroke, coronary events, or death. Even in the subgroup with the highest homocysteine levels, high-dose therapy was ineffective.

Comment: Homocysteine-lowering vitamins did not prevent recurrent stroke or coronary events in this large trial. Taken together with the negative results from the trial in patients with stable coronary disease cited above, B vitamins appear to be of limited value in secondary cardiovascular prevention. It remains possible, however, that longer duration of B vitamin supplementation could be beneficial in patients with extremely elevated homocysteine levels or for primary cardiovascular prevention.

— Allan S. Brett, MD

Published in Journal Watch General Medicine February 17, 2004

Citation(s):

Toole JF et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death. The Vitamin Intervention for Stroke Prevention (VISP) Randomized Controlled Trial. JAMA 2004 Feb 4; 291:565-75.

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