B Vitamins and Magnetic Resonance Imaging–Detected Ischemic Brain Lesions in Patients With Recent Transient Ischemic Attack or Stroke

Elevated blood concentrations of total homocysteine have been associated with cerebral small vessel disease (CSVD) as defined by clinical lacunar syndromes or brain magnetic resonance imaging (MRI) evidence of ischemic lesions in the vascular territories of the deep perforating small arteries. Homocysteine can be lowered by B-vitamin supplementation with folate alone or in combination with vitamins B 12 and B 6 . In a substudy of the VITAmins TO Prevent Stroke (VITATOPS) trial, we assessed the prespecified hypothesis Background and Purpose—Elevated concentrations of homocysteine are associated with cerebral small vessel disease (CSVD). B-vitamin supplementation with folate and vitamins B 12 and B 6 reduces homocysteine concentrations. In a substudy of the VITAmins TO Prevent Stroke (VITATOPS) trial, we assessed the hypothesis that the addition of oncedaily supplements of B vitamins would reduce the progression of CSVD-related brain lesions. Methods—A total of 359 patients with recent stroke or transient ischemic attack, who were randomly allocated to doubleblind treatment with placebo or B vitamins, underwent brain MRI at randomization and after 2 years of B-vitamin supplementation. MR images were analyzed blinded to treatment allocation. Outcomes related to the prespecified hypothesis were progression of white matter hyperintensities and incident lacunes. We also explored the effect of B-vitamin supplementation on the incidence of other ischemic abnormalities. Results—After 2 years of treatment with B vitamins or placebo, there was no significant difference in white matter hyperintensities volume change (0.08 vs 0.13 cm; P=0.419) and incidence of lacunes (8.0% vs 5.9%, P=0.434; odds ratio=1.38). In a subanalysis of patients with MRI evidence of severe CSVD at baseline, B-vitamin supplementation was associated with a significant reduction in white matter hyperintensities volume change (0.3 vs 1.7 cm; P=0.039). Conclusions—Daily B-vitamin supplementation for 2 years did not significantly reduce the progression of brain lesions resulting from presumed CSVD in all patients with recent stroke or transient ischemic attack but may do so in the subgroup of patients with recent stroke or transient ischemic attack and severe CSVD. Clinical Trial Registration—http://vitatops.highway1.com.au/. Unique identifier: NCT00097669 and ISRCTN74743444. (Stroke. 2012;43:3266-3270.)