In the Vitamin Intervention for Stroke Prevention (VISP) trial, therapy with high doses of vitamin B6 , vitamin , and folic acid did not affect the risk of recurrent isch- emic stroke compared with a low-dose formulation of these B complex vitamins. In 2 Norwegian trials, 1 trial of patients with MI and the other of patients with coronary artery disease or aortic stenosis, B complex vitamins did not reduce mortal- ity or cardiovascular events, including stroke.784,785 Similarly, in the Women s Antioxidant and Folic Acid Cardiovascular Study (WAFACS), these B complex vitamins did not alter the risk of stroke in women with established CVD or 3 risk fac- Most recently, the VITATOPS trial,787 in which 8164 subjects with recent stroke or TIA were randomized to vitamin , vitamin B12 , and folic acid versus placebo and followed up for a median of 3.4 years, found no effect of B vitamin supple- mentation on risk of stroke (HR, 0.92; 95% CI, 0.81 1.06). Interestingly, a post hoc analysis restricted to the 1463 sub- jects in VITATOPS not taking antiplatelet medication788 found a reduced risk of stroke in the B vitamin group (HR, 0.6; 95% CI, 0.50 0.95) and a significant interaction between anti- platelet use and assignment to B vitamins. It remains unclear whether the effectiveness of B vitamin treatment within the no-antiplatelet subgroup represents biological modification of the effects of homocysteine by antiplatelet drugs, intergroup differences between patients on and off antiplatelet therapy (such as the greater proportion of patients with hemorrhagic or cardioembolic strokes among those not taking antiplatelets), or a spurious result of secondary analysis. 