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Folate Therapy Harmful After Stenting

New data contradict previous findings.

An elevated homocysteine level, which is associated with coronary artery disease, can be lowered by use of folic-acid supplements. In a randomized placebo-controlled trial called the Swiss Heart Study, combination folate therapy (folic acid, vitamin B₆, and vitamin B₁₂) also reduced restenosis rates in patients who underwent coronary angioplasty (56% received stents); see Journal Watch Cardiology Jan 4 2002. A new trial refutes this finding.

The subjects, 636 patients who underwent successful coronary stenting, were randomized to an initial intravenous bolus and a 6-month oral regimen of either placebo or combination folate therapy. At 6 months, 483 patients underwent angiography (91 had discontinued treatment, 60 refused follow-up angiography, and 2 had died).

By 6 months, the mean homocysteine level had declined significantly in the folate group but not in the placebo group. Despite this apparent advantage, the folate group had a significantly smaller minimum luminal diameter at 6 months than the placebo group (mean, 1.59 mm vs. 1.74 mm), due to significantly greater late loss. Accordingly, the folate group had significantly higher rates of restenosis (35% vs. 27%) and target-vessel revascularization (16% vs. 11%). Folate's detrimental effect was most pronounced in nondiabetics, in men, and in patients with a low baseline homocysteine level.

Comment: Although some advocate folate therapy for secondary prevention in patients with high homocysteine levels, current federal guidelines do not support this practice, given a lack of clinical trial evidence. The current findings raise the disturbing possibility that a therapy previously considered safe may actually cause harm. Their inconsistency with the Swiss Heart Study findings might be due to differences in vitamin doses, patient and lesion characteristics, baseline homocysteine levels, and percentages of patients who received stents. For now, post-stenting folate supplementation cannot be routinely recommended. Furthermore, as drug-eluting stents are reducing the specific problem of restenosis, interventionists must refocus on treatments that attenuate atherosclerosis progression in general.

— Howard C. Herrmann, MD

Dr. Herrmann wrote the editorial that accompanied the original article.

Published in Journal Watch Cardiology August 13, 2004

Citation(s):

Lange H et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 2004 Jun 24; 350:2673-81.

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