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Homocysteine-Lowering Treatments for CVD?


Am Fam Physician. 2006 Nov 1;74(9):1606.

Observational studies indicate a positive association between high homocysteine levels and risk of cardiovascular disease (CVD). Folic acid and vitamins B6 and B12 are known to lower homocysteine levels. Two trials recently studied the effectiveness of these treatments for improving cardiovascular outcomes in high-risk patients.

The first trial involved 5,522 patients with known vascular disease or diabetes, with a combined primary outcome measure of cardiac death, myocardial infarction, and stroke. Participants were from 13 countries (with or without a folate-fortified food supply); they had an average age of 69 years, and about 70 percent were men. Participants were randomized to five years of treatment (2.5 mg folic acid, 50 mg vitamin B6 and 1mg vitamin B12) or placebo.

There were no significant differences in baseline plasma homocysteine levels at randomization. About 90 percent of patients were still taking the treatment at five years, and all but 37 completed the study. At the end of the study, although there was a decrease in the homocysteine levels in the treatment group, there was no significant difference in the primary outcome between the treatment and placebo groups.

The second trial included 3,749 Norwegian patients who had had a myocardial infarction. The average age was 63 years, and more than 70 percent were men. Participants were randomized within seven days of having a myocardial infarction to one of four groups: (1) 0.8mg folic acid, 0.4 mg vitamin B12, and 40 mg B6; (2) 0.8 mg folic acid and 0.4 mg vitamin B12; (3) 40mg B6; or (4) placebo.

The primary outcome in this trial was a combination of new myocardial infarction, stroke, and sudden cardiovascular death. Mean follow-up duration was three years. The groups treated with folic acid experienced a significant reduction in homocysteine, whereas the B6 and placebo groups did not. However, no treatment groups differed significantly from placebo in the primary outcome.

The findings of both studies do not support supplementation with folic acid and B vitamins for preventing cardiovascular events in high-risk patients.

The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med April 13, 2006;354:1567–77; and Bønaa KH, et al., for the NORVIT Trial Investigators. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. April 13, 2006;354:1578–88.



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