Folate therapy and in-stent restenosis after coronary stenting

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 B ₆, 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 B ₆, and vitamin B₁₂ after coronary stenting may increase the risk of in-stent restenosis and the need for target-vessel revascularization.