Folate Therapy After Coronary Stenting May Raise Restenosis Risk

Contrary to what has been shown in patients who undergo coronary angioplasty, the use of folate, vitamin B6, and vitamin B12 after coronary stenting appears to increase the risk of in-stent restenosis and the need for repeated target-vessel revascularization, new research suggests.

Previous reports have shown that by lowering homocysteine levels, this vitamin combination, referred to as folate therapy, can reduce the risk of adverse events after coronary interventions (see Reuters Health report August 27, 2002). However, while most of these studies indicated a protective effect for folate therapy after coronary angioplasty, the benefits after stenting were less clear.

To address this issue, Dr. Harry Suryapranata, from De Weezenlanden Hospital in Zwolle, the Netherlands, and colleagues assessed the outcomes of 636 patients who underwent coronary stenting and were randomized to receive folate therapy or placebo for 6 months.

The researchers’ findings are published in the June 24th issue of The New England Journal of Medicine.

At study end, the average minimal luminal diameter in the folate group was significantly smaller than in the control group (p = 0.008). In addition, late luminal loss was greater in the folate group (p = 0.004).

The restenosis rate in the folate group was 34.5%, while the rate in the control group was 26.5%, the investigators point out. Moreover, 15.8% of folate-treated patients required target-vessel revascularization compared with 10.6% of control patients (p = 0.05 for both). The adverse effect of folate therapy on restenosis rates was seen in all subgroups except women, diabetics, and patients with baseline homocysteine levels of at least 15 micromol/L.

The new findings “raise the disturbing possibility that a therapy that has previously been considered safe may actually be harmful,” Dr. Howard C. Herrmann, from the University of Pennsylvania in Philadelphia, notes in a related editorial. Further studies are needed to clarify which patients might benefit from folate therapy, but based on the present results, it should not be routinely used for patients receiving coronary stents, he adds.

N Engl J Med 2004;350:2673-2681,2708-2710.