Lowering homocysteine in patients with ischemic stroke to recurrent stroke, myocardial infarction, and death: The vitamin intervention for stroke prevention (VISP) randomized controlled trial

Abstract

Conclusion: Vitamin therapy resulting in moderate reductions of total homocysteine after a nondisabling cerebral event has no affect on vascular outcomes during a 2-year follow up period. Summary: The authors sought to determine if high doses of folic acid, pyridoxine (vitamin B6), and cobamalin (vitamin B12) could lower the risk of death, recurrent cerebral infarction, and coronary heart disease in patients with a nondisabling cerebral infarction. A total of 3680 adults with nondisabling cerebral infarction were randomized at 56 centers to receive best medical and surgical care plus a daily vitamin containing either high-dose formulations of pyridoxine (25 mg), cobamalin (0.4 mg), and folic acid (2.5 mg) or a low-dose formulations containing 200 μg of pyridoxine, 6 μg of cobamalin, and 20 μg of folic acid. There was a graded and persistent association between baseline total homocysteine level and outcome. Risk association with baseline homocysteine level was numerically slightly lower in the high-dose group for all events but was not statistically different from that in the low-dose group. Mean total homocysteine levels were reduced to a greater extent in the high-dose group than in the low-dose group (2 μmol/L). There were no differences in the high-dose or low-dose groups with respect to recurrent cerebral infarction, coronary heart disease, or death. There was an 18% chance of an event within 2 years in the high-dose vitamin group and an 18.6% chance of an event within 2 years in the low-dose vitamin group. The risk of ischemic stroke within 2 years was 9.2% for the high-dose and 8.8% for the low-dose group (P = .80). Comment: The lack of treatment effect of vitamin therapy on cardiovascular end points observed in this study may be due to several factors. Homocysteine levels in the study population were relatively low and treatment effects may be more pronounced in patients with higher levels of homocysteine. Alternatively, US government–mandated folic acid supplementation of the grain supply may have mitigated additional vitamin effects. A longer period of observation may also be necessary to observe treatment effect.