No Secondary-Prevention Benefit of Vitamin B Pills

No Secondary-Prevention Benefit of Vitamin B Pills

Supplementation lowered homocysteine levels but did not prevent cardiovascular events in patients with vascular disease.

In epidemiologic and observational studies, high homocysteine levels have been associated with increased cardiovascular risk. Two new randomized trials address whether lowering homocysteine levels with B vitamins reduces risk for cardiovascular events.

In the HOPE-2 trial, 5522 high-risk patients (with histories of documented vascular disease or with diabetes plus another risk factor) were randomized to receive either placebo or a single daily pill containing folic acid (2.5 mg), vitamin B₆ (50 mg), and vitamin B₁₂ (1 mg). All patients were age 55 or older. During 5 years of follow-up, mean homocysteine levels decreased by 2.4 µmol/L in the treatment group and increased by 0.8 µmol/L in the placebo group. However, incidence of the primary composite endpoint — MI, stroke, or death from cardiovascular causes — was similar in the two groups (18.8% and 19.8%, respectively).

In the Norwegian Vitamin Trial, 3749 patients with MI in the preceding week were randomized to one of four daily regimens: folic acid (0.8 mg), vitamin B₁₂ (0.4 mg), and vitamin B₆ (40 mg); just the folic acid and vitamin B₁₂; just the vitamin B₆; or placebo. During a mean follow-up of 3 years, mean homocysteine levels dropped by 3.4 µmol/L in the two groups who received folic acid and vitamin B₁₂, with virtually no change in the other groups. Supplementation of any type failed to reduce incidence of the primary endpoint (MI, stroke, or sudden death), even when patients were stratified according to baseline homocysteine levels (>13 vs. $≤$ 13 µmol/L). In fact, supplementation was associated with a nonsignificant trend toward worse outcomes.

Comment: These two studies confirm previous findings that patients with vascular disease do not benefit from vitamin B supplementation (Journal Watch Cardiology Aug 8 2003). Folic acid and B vitamins should not be used for secondary prevention of cardiovascular events. It’s worth exploring whether homocysteine-lowering by other means would have outcome benefits.

— JoAnne M. Foody, MD

Published in Journal Watch Cardiology December 27, 2006

Citation(s):

The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006 Apr 13; 354:1567-77.