N Engl J Med 2004, 350(26):2673-2681
Lange,H.; Suryapranata,H.; De Luca,G.; Borner,C.; Dille,J.; Kallmeyer,K.; Pasalary,M.; Scherer,E.; Dambrink,Jan-Henk
BACKGROUND: Vitamin therapy to lower homocysteine levels has recently been
recommended for the prevention of restenosis after coronary angioplasty. We tested the effect of a
combination of folic acid, vitamin B6, and vitamin B12 (referred to as folate therapy) on the risk of
angiographic restenosis after coronary-stent placement in a double-blind, multicenter trial.
METHODS: A total of 636 patients who had undergone successful coronary stenting
were randomly assigned to receive 1 mg of folic acid, 5 mg of vitamin B6, and 1 mg of vitamin B12
intravenously, followed by daily oral doses of 1.2 mg of folic acid, 48 mg of vitamin B6, and 60 µg of
vitamin B12 for six months, or to receive placebo. The angiographic end points (minimal luminal diameter,
late loss, and restenosis rate) were assessed at six months by means of quantitative coronary angiography.
RESULTS: At follow-up, the mean (±SD) minimal luminal diameter was significantly
smaller in the folate group than in the placebo group (1.59±0.62 mm vs. 1.74±0.64 mm, P=0.008), and the
extent of late luminal loss was greater (0.90±0.55 mm vs. 0.76±0.58 mm, P=0.004). The restenosis rate was
higher in the folate group than in the placebo group (34.5 percent vs. 26.5 percent, P=0.05), and a higher
percentage of patients in the folate group required repeated target-vessel revascularization (15.8 percent
vs. 10.6 percent, P=0.05). Folate therapy had adverse effects on the risk of restenosis in all subgroups
except for women, patients with diabetes, and patients with markedly elevated homocysteine levels (15 µmol
per liter or more) at baseline.
CONCLUSIONS: Contrary to previous findings, the administration of folate,
vitamin B6, and vitamin B12 after coronary stenting may increase the risk of in-stent restenosis and the
need for target-vessel revascularization.